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Extracellular Vesicles as Drug Delivery Systems in Organ Transplantation: The Next Frontier
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Micro-Scale Vacuum Compression Molding as a Predictive Screening Tool of Protein Integrity for Potential Hot-Melt Extrusion Processes
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Synergistic Antimicrobial Activity of Silver Nanoparticles with an Emergent Class of Azoimidazoles
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Tumor Spheroids as Model to Design Acoustically Mediated Drug Therapies: A Review
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Immunomodulatory Activity of the Tyrosine Kinase Inhibitor Dasatinib to Elicit NK Cytotoxicity against Cancer, HIV Infection and Aging
Journal Description
Pharmaceutics
Pharmaceutics
is a peer-reviewed, open access journal on the science and technology of pharmaceutics and biopharmaceutics, and is published monthly online by MDPI. The Spanish Society of Pharmaceutics and Pharmaceutical Technology (SEFIG), Pharmaceutical Solid State Research Cluster (PSSRC), Academy of Pharmaceutical Sciences (APS) and Korean Society of Pharmaceutical Sciences and Technology (KSPST) are affiliated with Pharmaceutics and their members receive a discount on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q1 (Pharmacology & Pharmacy) / CiteScore - Q2 (Pharmaceutical Science)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 15.9 days after submission; acceptance to publication is undertaken in 3.5 days (median values for papers published in this journal in the second half of 2022).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Companion journal: Future Pharmacology
Impact Factor:
6.525 (2021);
5-Year Impact Factor:
7.227 (2021)
Latest Articles
Influence of Surface-Modification via PEGylation or Chitosanization of Lipidic Nanocarriers on In Vivo Pharmacokinetic/Pharmacodynamic Profiles of Apixaban
Pharmaceutics 2023, 15(6), 1668; https://doi.org/10.3390/pharmaceutics15061668 (registering DOI) - 07 Jun 2023
Abstract
Nanostructured lipid carriers (NLCs) have been proven to significantly improve the bioavailability and efficacy of many drugs; however, they still have many limitations. These limitations could hinder their potential for enhancing the bioavailability of poorly water-soluble drugs and, therefore, require further amendments. From
[...] Read more.
Nanostructured lipid carriers (NLCs) have been proven to significantly improve the bioavailability and efficacy of many drugs; however, they still have many limitations. These limitations could hinder their potential for enhancing the bioavailability of poorly water-soluble drugs and, therefore, require further amendments. From this perspective, we have investigated how the chitosanization and PEGylation of NLCs affected their ability to function as a delivery system for apixaban (APX). These surface modifications could enhance the ability of NLCs to improve the bioavailability and pharmacodynamic activity of the loaded drug. In vitro and in vivo studies were carried out to examine APX-loaded NLCs, chitosan-modified NLCs, and PEGylated NLCs. The three nanoarchitectures displayed a Higuchi-diffusion release pattern in vitro, in addition to having their vesicular outline proven via electron microscopy. PEGylated and chitosanized NLCs retained good stability over 3 months, versus the nonPEGylated and nonchitosanized NLCs. Interestingly, APX-loaded chitosan-modified NLCs displayed better stability than the APX-loaded PEGylated NLCs, in terms of mean vesicle size after 90 days. On the other hand, the absorption profile of APX (AUC0-inf) in rats pretreated with APX-loaded PEGylated NLCs (108.59 µg·mL−1·h−1) was significantly higher than the AUC0-inf of APX in rats pretreated with APX-loaded chitosan-modified NLCs (93.397 µg·mL−1·h−1), and both were also significantly higher than AUC0-inf of APX-Loaded NLCs (55.435 µg·mL−1·h−1). Chitosan-coated NLCs enhanced APX anticoagulant activity with increased prothrombin time and activated partial thromboplastin time by 1.6- and 1.55-folds, respectively, compared to unmodified NLCs, and by 1.23- and 1.37-folds, respectively, compared to PEGylated NLCs. The PEGylation and chitosanization of NLCs enhanced the bioavailability and anticoagulant activity of APX over the nonmodified NLCs; this highlighted the importance of both approaches.
Full article
(This article belongs to the Special Issue Advanced Nanomaterials for Drug Delivery)
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The Long-Term Neuroprotective Effect of the Endocannabinoid 2-AG and Modulation of the SGZ’s Neurogenic Response after Neonatal Hypoxia-Ischemia
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, , , , , and
Pharmaceutics 2023, 15(6), 1667; https://doi.org/10.3390/pharmaceutics15061667 (registering DOI) - 07 Jun 2023
Abstract
Neonatal hypoxia-ischemia (HI) often causes hypoxic-ischemic encephalopathy (HIE), a neurological condition that can lead to overall disability in newborns. The only treatment available for affected neonates is therapeutic hypothermia; however, cooling is not always effective to prevent the deleterious effects of HI, so
[...] Read more.
Neonatal hypoxia-ischemia (HI) often causes hypoxic-ischemic encephalopathy (HIE), a neurological condition that can lead to overall disability in newborns. The only treatment available for affected neonates is therapeutic hypothermia; however, cooling is not always effective to prevent the deleterious effects of HI, so compounds such as cannabinoids are currently under research as new therapies. Modulating the endocannabinoid system (ECS) may reduce brain damage and/or stimulate cell proliferation at the neurogenic niches. Further, the long-term effects of cannabinoid treatment are not so clear. Here, we studied the middle- and long-term effects of 2-AG, the most abundant endocannabinoid in the perinatal period after HI in neonatal rats. At middle-term (postnatal day 14), 2-AG reduced brain injury and increased SGZ’s cell proliferation and the number of neuroblasts. At post-natal day 90, the treatment with the endocannabinoid showed global and local protection, suggesting long-lasting neuroprotective effects of 2-AG after neonatal HI in rats.
Full article
(This article belongs to the Special Issue Drugs in Pregnancy and Lactation—Volume II)
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Synthesis, Characterization, and Docking Study of Novel Thioureidophosphonate-Incorporated Silver Nanocomposites as Potent Antibacterial Agents
by
, , , , , , , and
Pharmaceutics 2023, 15(6), 1666; https://doi.org/10.3390/pharmaceutics15061666 (registering DOI) - 06 Jun 2023
Abstract
Newly synthesized mono- and bis-thioureidophosphonate (MTP and BTP) analogues in eco-friendly conditions were employed as reducing/capping cores for 100, 500, and 1000 mg L−1 of silver nitrate. The physicochemical properties of silver nanocomposites (MTP(BTP)/Ag NCs) were fully elucidated using spectroscopic and microscopic
[...] Read more.
Newly synthesized mono- and bis-thioureidophosphonate (MTP and BTP) analogues in eco-friendly conditions were employed as reducing/capping cores for 100, 500, and 1000 mg L−1 of silver nitrate. The physicochemical properties of silver nanocomposites (MTP(BTP)/Ag NCs) were fully elucidated using spectroscopic and microscopic tools. The antibacterial activity of the nanocomposites was screened against six multidrug-resistant pathogenic strains, comparable to ampicillin and ciprofloxacin commercial drugs. The antibacterial performance of BTP was more substantial than MTP, notably with the best minimum inhibitory concentration (MIC) of 0.0781 mg/mL towards Bacillus subtilis, Salmonella typhi, and Pseudomonas aeruginosa. Among all, BTP provided the clearest zone of inhibition (ZOI) of 35 ± 1.00 mm against Salmonella typhi. After the dispersion of silver nanoparticles (AgNPs), MTP/Ag NCs offered dose-dependently distinct advantages over the same nanoparticle with BTP; a more noteworthy decline by 4098 × MIC to 0.1525 × 10−3 mg/mL was recorded for MTP/Ag-1000 against Pseudomonas aeruginosa over BTP/Ag-1000. Towards methicillin-resistant Staphylococcus aureus (MRSA), the as-prepared MTP(BTP)/Ag-1000 displayed superior bactericidal ability in 8 h. Because of the anionic surface of MTP(BTP)/Ag-1000, they could effectively resist MRSA (ATCC-43300) attachment, achieving higher antifouling rates of 42.2 and 34.4% at most optimum dose (5 mg/mL), respectively. The tunable surface work function between MTP and AgNPs promoted the antibiofilm activity of MTP/Ag-1000 by 1.7 fold over BTP/Ag-1000. Lastly, the molecular docking studies affirmed the eminent binding affinity of BTP over MTP—besides the improved binding energy of MTP/Ag NC by 37.8%—towards B. subtilis-2FQT protein. Overall, this study indicates the immense potential of TP/Ag NCs as promising nanoscale antibacterial candidates.
Full article
(This article belongs to the Special Issue Focus on Antibiotics – New Challenges and Steps Forward in Discovery and Development (Volume II))
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Open AccessArticle
Development of a Gene and Nucleic Acid Delivery System for Skeletal Muscle Administration via Limb Perfusion Using Nanobubbles and Ultrasound
by
, , , , , , , , , , , , , and
Pharmaceutics 2023, 15(6), 1665; https://doi.org/10.3390/pharmaceutics15061665 - 06 Jun 2023
Abstract
Strategies for gene and nucleic acid delivery to skeletal muscles have been extensively explored to treat Duchenne muscular dystrophy (DMD) and other neuromuscular diseases. Of these, effective intravascular delivery of naked plasmid DNA (pDNA) and nucleic acids into muscles is an attractive approach,
[...] Read more.
Strategies for gene and nucleic acid delivery to skeletal muscles have been extensively explored to treat Duchenne muscular dystrophy (DMD) and other neuromuscular diseases. Of these, effective intravascular delivery of naked plasmid DNA (pDNA) and nucleic acids into muscles is an attractive approach, given the high capillary density in close contact with myofibers. We developed lipid-based nanobubbles (NBs) using polyethylene-glycol-modified liposomes and an echo-contrast gas and found that these NBs could improve tissue permeability by ultrasound (US)-induced cavitation. Herein, we delivered naked pDNA or antisense phosphorodiamidate morpholino oligomers (PMOs) into the regional hindlimb muscle via limb perfusion using NBs and US exposure. pDNA encoding the luciferase gene was injected with NBs via limb perfusion into normal mice with application of US. High luciferase activity was achieved in a wide area of the limb muscle. DMD model mice were administered PMOs, designed to skip the mutated exon 23 of the dystrophin gene, with NBs via intravenous limb perfusion, followed by US exposure. The number of dystrophin-positive fibers increased in the muscles of mdx mice. Combining NBs and US exposure, which can be widely delivered to the hind limb muscles via the limb vein, could be an effective therapeutic approach for DMD and other neuromuscular disorders.
Full article
(This article belongs to the Special Issue Ultrasound-Mediated Drug Delivery)
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Open AccessReview
Anatomical Targeting of Anticancer Drugs to Solid Tumors Using Specific Administration Routes: Review
Pharmaceutics 2023, 15(6), 1664; https://doi.org/10.3390/pharmaceutics15061664 - 06 Jun 2023
Abstract
Despite remarkable recent progress in developing anti-cancer agents, outcomes of patients with solid tumors remain unsatisfactory. In general, anti-cancer drugs are systemically administered through peripheral veins and delivered throughout the body. The major problem with systemic chemotherapy is insufficient uptake of intravenous (IV)
[...] Read more.
Despite remarkable recent progress in developing anti-cancer agents, outcomes of patients with solid tumors remain unsatisfactory. In general, anti-cancer drugs are systemically administered through peripheral veins and delivered throughout the body. The major problem with systemic chemotherapy is insufficient uptake of intravenous (IV) drugs by targeted tumor tissue. Although dose escalation and treatment intensification have been attempted in order to increase regional concentrations of anti-tumor drugs, these approaches have produced only marginal benefits in terms of patient outcomes, while often damaging healthy organs. To overcome this problem, local administration of anti-cancer agents can yield markedly higher drug concentrations in tumor tissue with less systemic toxicity. This strategy is most commonly used for liver and brain tumors, as well as pleural or peritoneal malignancies. Although the concept is theoretically reasonable, survival benefits are still limited. This review summarizes clinical results and problems and discusses future directions of regional cancer therapy with local administration of chemotherapeutants.
Full article
(This article belongs to the Special Issue Targeted Drug Delivery for Diagnostic and Therapeutic Applications)
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Open AccessEditorial
Magnetic Nanoparticles for Therapy and Diagnosis in Nanomedicine
Pharmaceutics 2023, 15(6), 1663; https://doi.org/10.3390/pharmaceutics15061663 - 06 Jun 2023
Abstract
Magnetic nanoparticles (MNPs) have been widely used for their potential applications, mainly for the diagnosis and/or therapy (theranostic) of several diseases in the field of nanomedicine, as passive contrast agents, through the opsonization process, or active contrast agents, after their functionalization and the
[...] Read more.
Magnetic nanoparticles (MNPs) have been widely used for their potential applications, mainly for the diagnosis and/or therapy (theranostic) of several diseases in the field of nanomedicine, as passive contrast agents, through the opsonization process, or active contrast agents, after their functionalization and the subsequent capture of the signal using various techniques such as magnetic resonance imaging (MRI), optical imaging, nuclear imaging, and ultrasound [...]
Full article
(This article belongs to the Special Issue Magnetic Nanoparticles for Therapy and Diagnosis in Nanomedicine)
Open AccessArticle
Development of Conjugated Kefiran-Chondroitin Sulphate Cryogels with Enhanced Properties for Biomedical Applications
by
, , , , and
Pharmaceutics 2023, 15(6), 1662; https://doi.org/10.3390/pharmaceutics15061662 - 05 Jun 2023
Abstract
Hydrogels based on natural polysaccharides can have unique properties and be tailored for several applications, which may be mainly limited by the fragile structure and weak mechanical properties of this type of system. We successfully prepared cryogels made of newly synthesized kefiran exopolysaccharide-chondroitin
[...] Read more.
Hydrogels based on natural polysaccharides can have unique properties and be tailored for several applications, which may be mainly limited by the fragile structure and weak mechanical properties of this type of system. We successfully prepared cryogels made of newly synthesized kefiran exopolysaccharide-chondroitin sulfate (CS) conjugate via carbodiimide-mediated coupling to overcome these drawbacks. The freeze-thawing procedure of cryogel preparation followed by lyophilization is a promising route to fabricate polymer-based scaffolds with countless and valuable biomedical applications. The novel graft macromolecular compound (kefiran-CS conjugate) was characterized through 1H-NMR and FTIR spectroscopy—which confirmed the structure of the conjugate, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)—which mirrored good thermal stability (degradation temperature of about 215 °C) and, finally, gel permeation chromatography–size exclusion chromatography (GPC-SEC)—which proved an increased molecular weight due to chemical coupling of kefiran with CS. At the same time, the corresponding cryogels physically crosslinked after the freeze-thawing procedure were investigated by scanning electron microscopy (SEM), Micro-CT, and dynamic rheology. The results revealed a prevalent contribution of elastic/storage component to the viscoelastic behavior of cryogels in swollen state, a micromorphology with micrometer-sized open pores fully interconnected, and high porosity (ca. 90%) observed for freeze-dried cryogels. Furthermore, the metabolic activity and proliferation of human adipose stem cells (hASCs), when cultured onto the developed kefiran-CS cryogel, was maintained at a satisfactory level over 72 h. Based on the results obtained, it can be inferred that the newly freeze-dried kefiran-CS cryogels possess a host of unique properties that render them highly suitable for use in tissue engineering, regenerative medicine, drug delivery, and other biomedical applications where robust mechanical properties and biocompatibility are crucial.
Full article
(This article belongs to the Special Issue Application Prospect of Hydrogels in the Treatment of Osteochondral Lesions)
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Pharmacogenetic Sex-Specific Effects of Methotrexate Response in Patients with Rheumatoid Arthritis
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, , , , , , , and
Pharmaceutics 2023, 15(6), 1661; https://doi.org/10.3390/pharmaceutics15061661 - 05 Jun 2023
Abstract
Methotrexate (MTX) is a commonly used drug for the treatment of rheumatoid arthritis (RA), but its effectiveness can vary greatly among patients. Pharmacogenetics, the study of how genetic variations can affect drug response, has the potential to improve the personalized treatment of RA
[...] Read more.
Methotrexate (MTX) is a commonly used drug for the treatment of rheumatoid arthritis (RA), but its effectiveness can vary greatly among patients. Pharmacogenetics, the study of how genetic variations can affect drug response, has the potential to improve the personalized treatment of RA by identifying genetic markers that can predict a patient’s response to MTX. However, the field of MTX pharmacogenetics is still in its early stages and there is a lack of consistency among studies. This study aimed to identify genetic markers associated with MTX efficacy and toxicity in a large sample of RA patients, and to investigate the role of clinical covariates and sex-specific effects. Our results have identified an association of ITPA rs1127354 and ABCB1 rs1045642 with response to MTX, polymorphisms of FPGS rs1544105, GGH rs1800909, and MTHFR genes with disease remission, GGH rs1800909 and MTHFR rs1801131 polymorphisms with all adverse events, and ADA rs244076 and MTHFR rs1801131 and rs1801133, However, clinical covariates were more important factors to consider when building predictive models. These findings highlight the potential of pharmacogenetics to improve personalized treatment of RA, but also emphasize the need for further research to fully understand the complex mechanisms involved.
Full article
(This article belongs to the Section Pharmacokinetics and Pharmacodynamics)
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Open AccessArticle
Chitosan-Based Thermogelling System for Nose-to-Brain Donepezil Delivery: Optimising Formulation Properties and Nasal Deposition Profile
by
, , , , , , , , , , , and
Pharmaceutics 2023, 15(6), 1660; https://doi.org/10.3390/pharmaceutics15061660 - 05 Jun 2023
Abstract
Donepezil nasal delivery strategies are being continuously investigated for advancing therapy in Alzheimer’s disease. The aim of this study was to develop a chitosan-based, donepezil-loaded thermogelling formulation tailored to meet all the requirements for efficient nose-to-brain delivery. A statistical design of the experiments
[...] Read more.
Donepezil nasal delivery strategies are being continuously investigated for advancing therapy in Alzheimer’s disease. The aim of this study was to develop a chitosan-based, donepezil-loaded thermogelling formulation tailored to meet all the requirements for efficient nose-to-brain delivery. A statistical design of the experiments was implemented for the optimisation of the formulation and/or administration parameters, with regard to formulation viscosity, gelling and spray properties, as well as its targeted nasal deposition within the 3D-printed nasal cavity model. The optimised formulation was further characterised in terms of stability, in vitro release, in vitro biocompatibility and permeability (using Calu-3 cells), ex vivo mucoadhesion (using porcine nasal mucosa), and in vivo irritability (using slug mucosal irritation assay). The applied research design resulted in the development of a sprayable donepezil delivery platform characterised by instant gelation at 34 °C and olfactory deposition reaching a remarkably high 71.8% of the applied dose. The optimised formulation showed prolonged drug release (t1/2 about 90 min), mucoadhesive behaviour, and reversible permeation enhancement, with a 20-fold increase in adhesion and a 1.5-fold increase in the apparent permeability coefficient in relation to the corresponding donepezil solution. The slug mucosal irritation assay demonstrated an acceptable irritability profile, indicating its potential for safe nasal delivery. It can be concluded that the developed thermogelling formulation showed great promise as an efficient donepezil brain-targeted delivery system. Furthermore, the formulation is worth investigating in vivo for final feasibility confirmation.
Full article
(This article belongs to the Special Issue Challenges and Innovative Solutions in Nasal Drug Delivery: From Formulation Development to Mode of Administration)
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Open AccessArticle
Wettability of Amino Acid-Functionalized PSMA Electrospun Fibers for the Modulated Release of Active Agents and Its Effect on Their Bioactivity
by
, , , , , , , , , , and
Pharmaceutics 2023, 15(6), 1659; https://doi.org/10.3390/pharmaceutics15061659 - 05 Jun 2023
Abstract
The ideal treatment for chronic wounds is based on the use of bioactive dressings capable of releasing active agents. However, the control of the rate at which these active agents are released is still a challenge. Bioactive polymeric fiber mats of poly(styrene-co
[...] Read more.
The ideal treatment for chronic wounds is based on the use of bioactive dressings capable of releasing active agents. However, the control of the rate at which these active agents are released is still a challenge. Bioactive polymeric fiber mats of poly(styrene-co-maleic anhydride) [PSMA] functionalized with amino acids of different hydropathic indices and L-glutamine, L-phenylalanine and L-tyrosine levels allowed obtaining derivatives of the copolymers named [email protected], [email protected] and [email protected], respectively, with the aim of modulating the wettability of the mats. The bioactive characteristics of mats were obtained by the incorporation of the active agents Calendula officinalis (Cal) and silver nanoparticles (AgNPs). A higher wettability for [email protected] was observed, which is in accordance with the hydropathic index value of the amino acid. However, the release of AgNPs was higher for PSMA and more controlled for functionalized PSMA (PSMAf), while the release curves of Cal did not show behavior related to the wettability of the mats due to the apolar character of the active agent. Finally, the differences in the wettability of the mats also affected their bioactivity, which was evaluated in bacterial cultures of Staphylococcus aureus ATCC 25923 and methicillin-resistant Staphylococcus aureus ATCC 33592, an NIH/3T3 fibroblast cell line and red blood cells.
Full article
(This article belongs to the Special Issue Electrospun Fibers: Advancement in Drug Delivery, Controlled Release, and Tissue Regeneration)
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Open AccessArticle
Phosphorylcholine and KR12-Containing Corneal Implants in HSV-1-Infected Rabbit Corneas
by
, , , , , , , , , , , , , and
Pharmaceutics 2023, 15(6), 1658; https://doi.org/10.3390/pharmaceutics15061658 - 05 Jun 2023
Abstract
Severe HSV-1 infection can cause blindness due to tissue damage from severe inflammation. Due to the high risk of graft failure in HSV-1-infected individuals, cornea transplantation to restore vision is often contraindicated. We tested the capacity for cell-free biosynthetic implants made from recombinant
[...] Read more.
Severe HSV-1 infection can cause blindness due to tissue damage from severe inflammation. Due to the high risk of graft failure in HSV-1-infected individuals, cornea transplantation to restore vision is often contraindicated. We tested the capacity for cell-free biosynthetic implants made from recombinant human collagen type III and 2-methacryloyloxyethyl phosphorylcholine (RHCIII-MPC) to suppress inflammation and promote tissue regeneration in the damaged corneas. To block viral reactivation, we incorporated silica dioxide nanoparticles releasing KR12, the small bioactive core fragment of LL37, an innate cationic host defense peptide produced by corneal cells. KR12 is more reactive and smaller than LL37, so more KR12 molecules can be incorporated into nanoparticles for delivery. Unlike LL37, which was cytotoxic, KR12 was cell-friendly and showed little cytotoxicity at doses that blocked HSV-1 activity in vitro, instead enabling rapid wound closure in cultures of human epithelial cells. Composite implants released KR12 for up to 3 weeks in vitro. The implant was also tested in vivo on HSV-1-infected rabbit corneas where it was grafted by anterior lamellar keratoplasty. Adding KR12 to RHCIII-MPC did not reduce HSV-1 viral loads or the inflammation resulting in neovascularization. Nevertheless, the composite implants reduced viral spread sufficiently to allow stable corneal epithelium, stroma, and nerve regeneration over a 6-month observation period.
Full article
(This article belongs to the Special Issue Advances in Drug Delivery Systems and Therapies for Ocular Disorders)
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Open AccessArticle
Visualization and Estimation of Nasal Spray Delivery to Olfactory Mucosa in an Image-Based Transparent Nasal Model
Pharmaceutics 2023, 15(6), 1657; https://doi.org/10.3390/pharmaceutics15061657 - 05 Jun 2023
Abstract
Background: Nose-to-brain (N2B) drug delivery offers unique advantages over intravenous methods; however, the delivery efficiency to the olfactory region using conventional nasal devices and protocols is low. This study proposes a new strategy to effectively deliver high doses to the olfactory region while
[...] Read more.
Background: Nose-to-brain (N2B) drug delivery offers unique advantages over intravenous methods; however, the delivery efficiency to the olfactory region using conventional nasal devices and protocols is low. This study proposes a new strategy to effectively deliver high doses to the olfactory region while minimizing dose variability and drug losses in other regions of the nasal cavity. Materials and Methods: The effects of delivery variables on the dosimetry of nasal sprays were systematically evaluated in a 3D-printed anatomical model that was generated from a magnetic resonance image of the nasal airway. The nasal model comprised four parts for regional dose quantification. A transparent nasal cast and fluorescent imaging were used for visualization, enabling detailed examination of the transient liquid film translocation, real-time feedback on input effect, and prompt adjustment to delivery variables, which included the head position, nozzle angle, applied dose, inhalation flow, and solution viscosity. Results: The results showed that the conventional vertex-to-floor head position was not optimal for olfactory delivery. Instead, a head position tilting 45–60° backward from the supine position gave a higher olfactory deposition and lower variability. A two-dose application (250 mg) was necessary to mobilize the liquid film that often accumulated in the front nose following the first dose administration. The presence of an inhalation flow reduced the olfactory deposition and redistributed the sprays to the middle meatus. The recommended olfactory delivery variables include a head position ranging 45–60°, a nozzle angle ranging 5–10°, two doses, and no inhalation flow. With these variables, an olfactory deposition fraction of 22.7 ± 3.7% was achieved in this study, with insignificant discrepancies in olfactory delivery between the right and left nasal passages. Conclusions: It is feasible to deliver clinically significant doses of nasal sprays to the olfactory region by leveraging an optimized combination of delivery variables.
Full article
(This article belongs to the Special Issue Challenges and Innovative Solutions in Nasal Drug Delivery: From Formulation Development to Mode of Administration)
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Open AccessFeature PaperReview
Recent Advances in Nanoformulations for Quercetin Delivery
by
, , , , and
Pharmaceutics 2023, 15(6), 1656; https://doi.org/10.3390/pharmaceutics15061656 - 05 Jun 2023
Abstract
Quercetin (QUE) is a flavonol that has recently received great attention from the research community due to its important pharmacological properties. However, QUE’s low solubility and extended first-pass metabolism limit its oral administration. This review aims to present the potential of various nanoformulations
[...] Read more.
Quercetin (QUE) is a flavonol that has recently received great attention from the research community due to its important pharmacological properties. However, QUE’s low solubility and extended first-pass metabolism limit its oral administration. This review aims to present the potential of various nanoformulations in the development of QUE dosage forms for bioavailability enhancement. Advanced drug delivery nanosystems can be used for more efficient encapsulation, targeting, and controlled release of QUE. An overview of the primary nanosystem categories, formulation processes, and characterization techniques are described. In particular, lipid-based nanocarriers, such as liposomes, nanostructured-lipid carries, and solid-lipid nanoparticles, are widely used to improve QUE’s oral absorption and targeting, increase its antioxidant activity, and ensure sustained release. Moreover, polymer-based nanocarriers exhibit unique properties for the improvement of the Absorption, Distribution, Metabolism, Excretion, and Toxicology (ADME(T)) profile. Namely, micelles and hydrogels composed of natural or synthetic polymers have been applied in QUE formulations. Furthermore, cyclodextrin, niosomes, and nanoemulsions are proposed as formulation alternatives for administration via different routes. This comprehensive review provides insight into the role of advanced drug delivery nanosystems for the formulation and delivery of QUE.
Full article
(This article belongs to the Special Issue Recent Advances in Nanodelivery Systems for Plant and Food Derivatives)
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Open AccessPerspective
Polymers and Bioactive Compounds with a Macrophage Modulation Effect for the Rational Design of Hydrogels for Skin Regeneration
Pharmaceutics 2023, 15(6), 1655; https://doi.org/10.3390/pharmaceutics15061655 - 05 Jun 2023
Abstract
The development of biomaterial platforms for dispensing reagents of interest such as antioxidants, growth factors or antibiotics based on functional hydrogels represents a biotechnological solution for many challenges that the biomedicine field is facing. In this context, in situ dosing of therapeutic components
[...] Read more.
The development of biomaterial platforms for dispensing reagents of interest such as antioxidants, growth factors or antibiotics based on functional hydrogels represents a biotechnological solution for many challenges that the biomedicine field is facing. In this context, in situ dosing of therapeutic components for dermatological injuries such as diabetic foot ulcers is a relatively novel strategy to improve the wound healing process. Hydrogels have shown more comfort for the treatment of wounds due to their smooth surface and moisture, as well as their structural affinity with tissues in comparison to hyperbaric oxygen therapy, ultrasound, and electromagnetic therapies, negative pressure wound therapy or skin grafts. Macrophages, one of the most important cells of the innate immune system, have been described as the key not only in relation to the host immune defense, but also in the progress of wound healing. Macrophage dysfunction in chronic wounds of diabetic patients leads to a perpetuating inflammatory environment and impairs tissue repair. Modulating the macrophage phenotype from pro-inflammatory (M1) to anti-inflammatory (M2) could be a strategy for helping to improve chronic wound healing. In this regard, a new paradigm is found in the development of advanced biomaterials capable of inducing in situ macrophage polarization to offer an approach to wound care. Such an approach opens a new direction for the development of multifunctional materials in regenerative medicine. This paper surveys emerging hydrogel materials and bioactive compounds being investigated to induce the immunomodulation of macrophages. We propose four potential functional biomaterials for wound healing applications based on novel biomaterial/bioactive compound combination that are expected to show synergistic beneficial outcomes for the local differentiation of macrophages (M1–M2) as a therapeutic strategy for chronic wound healing improvement.
Full article
(This article belongs to the Special Issue Biopolymer Materials for Wound Healing (Volume II))
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Open AccessArticle
Mesenchymal Stem Cell Membrane-Coated TPCS2a-Loaded Nanoparticles for Breast Cancer Photodynamic Therapy
by
, , , , and
Pharmaceutics 2023, 15(6), 1654; https://doi.org/10.3390/pharmaceutics15061654 - 04 Jun 2023
Abstract
Despite substantial improvements in breast cancer (BC) treatment there is still an urgent need to find alternative treatment options to improve the outcomes for patients with advanced-stage disease. Photodynamic therapy (PDT) is gaining a lot of attention as a BC therapeutic option because
[...] Read more.
Despite substantial improvements in breast cancer (BC) treatment there is still an urgent need to find alternative treatment options to improve the outcomes for patients with advanced-stage disease. Photodynamic therapy (PDT) is gaining a lot of attention as a BC therapeutic option because of its selectivity and low off-target effects. However, the hydrophobicity of photosensitizers (PSs) impairs their solubility and limits the circulation in the bloodstream, thus representing a major challenge. The use of polymeric nanoparticles (NPs) to encapsulate the PS may represent a valuable strategy to overcome these issues. Herein, we developed a novel biomimetic PDT nanoplatform (NPs) based on a polymeric core of poly(lactic-co-glycolic)acid (PLGA) loaded with the PS meso-tetraphenylchlorin disulfonate (TPCS2a). TPCS2a@NPs of 98.89 ± 18.56 nm with an encapsulation efficiency percentage (EE%) of 81.9 ± 7.92% were obtained and coated with mesenchymal stem cells-derived plasma membranes (mMSCs) (mMSC-TPCS2a@NPs, size of 139.31 ± 12.94 nm). The mMSC coating armed NPs with biomimetic features to impart long circulation times and tumor-homing capabilities. In vitro, biomimetic mMSC-TPCS2a@NPs showed a decrease in macrophage uptake of 54% to 70%, depending on the conditions applied, as compared to uncoated TPCS2a@NPs. Both NP formulations efficiently accumulated in MCF7 and MDA-MB-231 BC cells, while the uptake was significantly lower in normal breast epithelial MCF10A cells with respect to tumor cells. Moreover, encapsulation of TPCS2a in mMSC-TPCS2a@NPs effectively prevents its aggregation, ensuring efficient singlet oxygen (1O2) production after red light irradiation, which resulted in a considerable in vitro anticancer effect in both BC cell monolayers (IC50 < 0.15 µM) and three-dimensional spheroids.
Full article
(This article belongs to the Special Issue Study of Nanoparticles for Photodynamic Therapy and Imaging)
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Open AccessReview
Combination Therapy as a Promising Way to Fight Oral Cancer
Pharmaceutics 2023, 15(6), 1653; https://doi.org/10.3390/pharmaceutics15061653 - 04 Jun 2023
Abstract
Oral cancer is a highly aggressive tumor with invasive properties that can lead to metastasis and high mortality rates. Conventional treatment strategies, such as surgery, chemotherapy, and radiation therapy, alone or in combination, are associated with significant side effects. Currently, combination therapy has
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Oral cancer is a highly aggressive tumor with invasive properties that can lead to metastasis and high mortality rates. Conventional treatment strategies, such as surgery, chemotherapy, and radiation therapy, alone or in combination, are associated with significant side effects. Currently, combination therapy has become the standard practice for the treatment of locally advanced oral cancer, emerging as an effective approach in improving outcomes. In this review, we present an in-depth analysis of the current advancements in combination therapies for oral cancer. The review explores the current therapeutic options and highlights the limitations of monotherapy approaches. It then focuses on combinatorial approaches that target microtubules, as well as various signaling pathway components implicated in oral cancer progression, namely, DNA repair players, the epidermal growth factor receptor, cyclin-dependent kinases, epigenetic readers, and immune checkpoint proteins. The review discusses the rationale behind combining different agents and examines the preclinical and clinical evidence supporting the effectiveness of these combinations, emphasizing their ability to enhance treatment response and overcome drug resistance. Challenges and limitations associated with combination therapy are discussed, including potential toxicity and the need for personalized treatment approaches. A future perspective is also provided to highlight the existing challenges and possible resolutions toward the clinical translation of current oral cancer therapies.
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(This article belongs to the Special Issue Novel Anticancer Strategies (Volume III))
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Open AccessArticle
Moisture Behavior of Pharmaceutical Powder during the Tableting Process
Pharmaceutics 2023, 15(6), 1652; https://doi.org/10.3390/pharmaceutics15061652 - 04 Jun 2023
Abstract
The moisture content of pharmaceutical powder is a key parameter contributing to tablet sticking during the tableting process. This study investigates powder moisture behavior during the compaction phase of the tableting process. Finite element analysis software COMSOL Multiphysics® 5.6 was used to
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The moisture content of pharmaceutical powder is a key parameter contributing to tablet sticking during the tableting process. This study investigates powder moisture behavior during the compaction phase of the tableting process. Finite element analysis software COMSOL Multiphysics® 5.6 was used to simulate the compaction microcrystalline cellulose (VIVAPUR PH101) powder and predict temperature and moisture content distributions, as well as their evolution over time, during a single compaction. To validate the simulation, a near-infrared sensor and a thermal infrared camera were used to measure tablet surface temperature and surface moisture, respectively, just after ejection. The partial least squares regression (PLS) method was used to predict the surface moisture content of the ejected tablet. Thermal infrared camera images of the ejected tablet showed powder bed temperature increasing during compaction and a gradual rise in tablet temperature along with tableting runs. Simulation results showed that moisture evaporate from the compacted powder bed to the surrounding environment. The predicted surface moisture content of ejected tablets after compaction was higher compared to that of loose powder and decreased gradually as tableting runs increased. These observations suggest that the moisture evaporating from the powder bed accumulates at the interface between the punch and tablet surface. Evaporated water molecules can be physiosorbed on the punch surface and cause a capillary condensation locally at the punch and tablet interface during dwell time. Locally formed capillary bridge may induce a capillary force between tablet surface particles and the punch surface and cause the sticking.
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(This article belongs to the Special Issue Pharmaceutical Tablets: Tablet Surface Preparation and Analysis Methods)
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Open AccessArticle
Two-Step Preparation of Protein-Decorated Biohybrid Quantum Dot Nanoparticles for Cellular Uptake
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Pharmaceutics 2023, 15(6), 1651; https://doi.org/10.3390/pharmaceutics15061651 - 03 Jun 2023
Abstract
Decoration of nanoparticles with specific molecules such as antibodies, peptides, and proteins that preserve their biological properties is essential for the recognition and internalization of their specific target cells. Inefficient preparation of such decorated nanoparticles leads to nonspecific interactions diverting them from their
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Decoration of nanoparticles with specific molecules such as antibodies, peptides, and proteins that preserve their biological properties is essential for the recognition and internalization of their specific target cells. Inefficient preparation of such decorated nanoparticles leads to nonspecific interactions diverting them from their desired target. We report a simple two-step procedure for the preparation of biohybrid nanoparticles containing a core of hydrophobic quantum dots coated with a multilayer of human serum albumin. These nanoparticles were prepared by ultra-sonication, crosslinked using glutaraldehyde, and decorated with proteins such as human serum albumin or human transferrin in their native conformations. These nanoparticles were homogeneous in size (20–30 nm), retained the fluorescent properties of quantum dots, and did not show a “corona effect” in the presence of serum. The uptake of transferrin-decorated quantum dot nanoparticles was observed in A549 lung cancer and SH-SY5Y neuroblastoma cells but not in non-cancerous 16HB14o- or retinoic acid dopaminergic neurons differentiated SH-SY5Y cells. Furthermore, digitoxin-loaded transferrin-decorated nanoparticles decreased the number of A549 cells without effect on 16HB14o-. Finally, we analyzed the in vivo uptake of these biohybrids by murine retinal cells, demonstrating their capacity to selectively target and deliver into specific cell types with excellent traceability.
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(This article belongs to the Special Issue Nanogels and Nanoparticles for Selective Drug Delivery)
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Open AccessReview
Updates on Biogenic Metallic and Metal Oxide Nanoparticles: Therapy, Drug Delivery and Cytotoxicity
Pharmaceutics 2023, 15(6), 1650; https://doi.org/10.3390/pharmaceutics15061650 - 03 Jun 2023
Abstract
The ambition to combat the issues affecting the environment and human health triggers the development of biosynthesis that incorporates the production of natural compounds by living organisms via eco-friendly nano assembly. Biosynthesized nanoparticles (NPs) have various pharmaceutical applications, such as tumoricidal, anti-inflammatory, antimicrobials,
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The ambition to combat the issues affecting the environment and human health triggers the development of biosynthesis that incorporates the production of natural compounds by living organisms via eco-friendly nano assembly. Biosynthesized nanoparticles (NPs) have various pharmaceutical applications, such as tumoricidal, anti-inflammatory, antimicrobials, antiviral, etc. When combined, bio-nanotechnology and drug delivery give rise to the development of various pharmaceutics with site-specific biomedical applications. In this review, we have attempted to summarize in brief the types of renewable biological systems used for the biosynthesis of metallic and metal oxide NPs and the vital contribution of biogenic NPs as pharmaceutics and drug carriers simultaneously. The biosystem used for nano assembly further affects the morphology, size, shape, and structure of the produced nanomaterial. The toxicity of the biogenic NPs, because of their pharmacokinetic behavior in vitro and in vivo, is also discussed, together with some recent achievements towards enhanced biocompatibility, bioavailability, and reduced side effects. Because of the large biodiversity, the potential biomedical application of metal NPs produced via natural extracts in biogenic nanomedicine is yet to be explored.
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(This article belongs to the Special Issue Biomedical Applications and Biosafety Assessment of Biologically Fabricated Nanomaterials)
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Open AccessReview
Electrospun Drug-Loaded and Gene-Loaded Nanofibres: The Holy Grail of Glioblastoma Therapy?
Pharmaceutics 2023, 15(6), 1649; https://doi.org/10.3390/pharmaceutics15061649 - 03 Jun 2023
Abstract
To date, GBM remains highly resistant to therapies that have shown promising effects in other cancers. Therefore, the goal is to take down the shield that these tumours are using to protect themselves and proliferate unchecked, regardless of the advent of diverse therapies.
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To date, GBM remains highly resistant to therapies that have shown promising effects in other cancers. Therefore, the goal is to take down the shield that these tumours are using to protect themselves and proliferate unchecked, regardless of the advent of diverse therapies. To overcome the limitations of conventional therapy, the use of electrospun nanofibres encapsulated with either a drug or gene has been extensively researched. The aim of this intelligent biomaterial is to achieve a timely release of encapsulated therapy to exert the maximal therapeutic effect simultaneously eliminating dose-limiting toxicities and activating the innate immune response to prevent tumour recurrence. This review article is focused on the developing field of electrospinning and aims to describe the different types of electrospinning techniques in biomedical applications. Each technique describes how not all drugs or genes can be electrospun with any method; their physico-chemical properties, site of action, polymer characteristics and the desired drug or gene release rate determine the strategy used. Finally, we discuss the challenges and future perspectives associated with GBM therapy.
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(This article belongs to the Section Drug Delivery and Controlled Release)
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