Search Results (121)

Objectives: This study aimed to develop and evaluate nanostructured lipid carriers (NLCs) loaded with meloxicam (Melox) and a therapeutic antibacterial and anti-inflammatory liquid lipid, clove oil (CO) for periodontitis treatment, a complex inflammatory condition necessitating advanced drug delivery systems. The NLC–Melox formulation was integrated into three hydrogels, hypromellose (HPMC), zinc hyaluronate (ZnHA), and sodium hyaluronate (NaHA), to conduct a comparative analysis focusing on enhanced localized drug delivery, improved mucoadhesion, prolonged retention, and significant therapeutic outcomes. Methods: NLC–Melox was prepared by homogenization and characterized by dynamic light scattering (DLS). Subsequently, NLC–Melox-loaded gels were subjected to transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), Raman spectroscopy, and rheological analysis. In vitro drug release, anti-inflammatory activity (BSA denaturation assay), and antibacterial efficacy (MIC, MBC) were investigated to assess therapeutic potential. Results: DLS revealed a particle size of 183 nm with a polydispersity index of 0.26, indicating homogeneity. TEM confirmed consistent morphology and uniform nanoparticle distribution. DSC and XRD demonstrated the amorphous nature of Melox, enhancing solubility and stability. Spectroscopy confirmed no chemical interactions between components. Rheological studies identified ZnHA as the most mucoadhesive and structurally stable gel. In vitro release studies showed sustained drug release over 24 h. Melox and CO-loaded formulations demonstrated significant anti-inflammatory activity and notable antibacterial efficacy due to the antibacterial oil. Conclusions: The study highlighted the potential of NLC-based mucoadhesive hydrogels as an effective strategy for periodontitis treatment. The formulation offered improved drug solubility, therapeutic efficacy, mucoadhesivity, and prolonged delivery, making it a promising candidate for localized therapy. Full article

Background: Folic acid (FA) is essential for cellular functions but has limited ocular bioavailability, restricting its therapeutic effectiveness. Objective: To develop chitosan (CS)-based nanogels (NGs) for FA transport and release, with corneal permeation evaluation. Methods: NGs’ hydrodynamic diameter (Ho) and polydispersity index (PdI) were determined using dynamic light scattering (DLS). CS-FA interaction was confirmed by Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA) was applied for the dehydrated material characterization. Scanning electron microscopy (SEM) was used to evaluate the NGs ultraestructure. In vitro drug release studies were performed using a modified Franz diffusion cell, and the release profile was fitted to obtain kinetics parameters. Mucoadhesion properties were evaluated through ζ-potential measurements. Ex vivo corneal permeation studies were conducted in rabbit corneas to compare the permeability of FA contained in NGs. Results: NGs presented a Ho of 312.4 ± 8.2 nm and a PdI of 0.28 ± 0.04. SEM imaging revealed spherical morphologies with minor variations in size and shape induced by FA. Lyophilized and resuspended NGs exhibited a 6.8% increase in Ho and a PdI rise to 0.42, indicating slight aggregation. In vitro drug release studies demonstrated sustained FA release, as determined by the Higuchi model. Mucoadhesion studies showed a decrease in ζ-potential from +36.9 to +18.1 mV, confirming electrostatic interactions with mucin. Ex vivo corneal permeation studies indicated that encapsulated FA permeated 2.6 times slower than free FA, suggesting sustained release. Conclusions: our findings demonstrate the potential of nanostructures in the form of NGs to enhance FA-loaded ocular delivery and bioavailability. Full article

Background: Captopril (CAP), an angiotensin-converting enzyme inhibitor (ACEI), is widely prescribed for managing hypertension, heart failure, and related conditions. When administered orally, CAP undergoes hepatic metabolism, resulting in a bioavailability of 60–75%. However, to bypass the first-pass metabolism and other limitations of the oral route, mucoadhesive buccal films have gained attention as a promising alternative with several advantages. The aim of this work was the formulation and optimization of chitosan-ascorbate mucoadhesive films for buccal delivery of CAP for the management of a hypertension crisis (10 mg and 20 mg) by employing quality by design (QbD) principles and the design of experiment (DoE) approach. Materials and methods: In the present work, chitosan (CHI) was selected as a film-forming agent due to its permeability-enhancing properties, which could be further improved through salification with ascorbic acid (AA). The polymer films were prepared by the solvent casting method. Results: The optimized CAP-loaded formula showed appropriate in vitro mucoadhesion force (>15 N) and breaking hardness (>14 N). The different CAP-containing films had a high drug content (>95%) with homogeneous drug distribution, thus complying with the requirements of Pharmacopeia. FT-IR and RAMAN spectroscopy analyses demonstrated successful incorporation of the drug, and interaction was observed between the excipients of the films, especially in the form of hydrogen bonds. The dissolution test showed immediate release of the API with a similar release pattern from both concentrations of CAP-loaded films. Conclusions: The properties of the prepared films met the predetermined critical quality attribute requirements. The optimized formula of CHI 1.4%, AA 2.5%, and glycerol 0.3% appears to be a promising buccal drug delivery system for CAP. Full article

Peptide and protein (PP) therapeutics are highly specific and potent biomolecules that treat chronic and complex diseases. However, their oral delivery is significantly hindered by enzymatic degradation, instability, and poor permeability through the gastrointestinal (GI) epithelium, resulting in low bioavailability. Various strategies have emerged as transformative solutions to address existing challenges, offering enhanced protection, stabilization, and absorption of PPs. These strategies primarily focus on two major challenges: protecting the PP against harsh conditions and enhancing permeation across the intestinal membrane. Innovative approaches such as pH modulation and incorporation of enzyme inhibitors are usually used to mitigate proteolytic degradation of PP during transit across the GI tract. In a similar vein, absorption enhancers and prodrug strategies facilitate epithelial transport, while targeted delivery systems focus on specific areas of the GI tract to enhance absorption. Likewise, mucus-penetrating and mucoadhesive strategies have enhanced retention and interaction with epithelial cells, effectively overcoming barriers like the mucus layer and tight epithelial junctions. Furthermore, structural modifications such as lipidation, peptide cyclization, and polyethylene glycosylation are promising alternatives to render stability, prolong circulation time, and membrane permeability. In particular, functional biomaterials, active targeting, and lymphatic transport strategies have provided new platforms for oral PP delivery. Advancing in materials science, nanotechnology, and the disruption of medical devices holds new frontiers to overcome barriers. Despite substantial advancements, the limited success in clinical translation underscores the urgency of innovative strategies. This review presents oral PPs as a promising platform, highlighting the key barriers and strategies to transform their therapeutic landscapes. Full article

Donepezil (DH), a selective acetylcholinesterase inhibitor, is widely used to manage symptoms of mild to moderate Alzheimer’s disease by enhancing cholinergic neurotransmission and preventing acetylcholine breakdown. Despite the effectiveness of oral formulations, extensive hepatic metabolism and low systemic bioavailability have driven the search for alternative delivery systems. This study focuses on nasal delivery as a non-parenteral substitute, utilizing hydroxypropyl methylcellulose (HPMC) for its mucoadhesive properties and methyl-β-cyclodextrin (Me-β-CD) for its ability to enhance permeability and form inclusion complexes with drugs. Prior studies demonstrated the potential of HPMC-based nasal films for nose-to-brain delivery of donepezil and highlighted Me-β-CD’s role in improving drug solubility. Building on this, transparent gel formulations containing DH, HPMC, and 2,6 Me-β-CD were developed to investigate molecular interactions within two- and three-component systems. This study utilized a combination of nuclear magnetic resonance (NMR) spectroscopy and density functional theory (DFT) to provide detailed insights into the interactions between DH, 2,6-Me-β-CD, and HPMC. The findings provide critical insights into drug–excipient interactions, aiding the optimization of stability, solubility, and controlled release. This advances the rational design of nanotechnology-based drug delivery systems for enhanced therapeutic efficacy. Full article

Background: Sirtuin-1 (SIRT1), a histone deacetylase enzyme expressed in ocular tissues with intracellular localization, plays a critical protective role against various degenerative ocular diseases. The link between reduced SIRT1 levels and diabetic retinopathy (DR) has prompted the exploration of natural therapeutic compounds that act as SIRT1 agonists. Curcumin (CUR), which has been shown to upregulate SIRT1 expression, is one such promising compound. However, effective delivery of CUR to the deeper ocular tissues, particularly the retina, remains a challenge due to its poor solubility and limited ocular penetration following topical administration. Within this context, the development of self-nanoemulsifying drug delivery systems (SNEDDS) for CUR topical ocular delivery represents a novel approach. Methods: In accordance with our prior research, optimized SNEDDS loaded with CUR were developed and characterized post-reconstitution with simulated tear fluid (STF) at a 1:10 ratio, showing suitable physicochemical and technological parameters for ocular delivery. Results: An entrapment efficiency (EE%) of approximately 99% and an absence of drug precipitation were noticed upon resuspension with STF. CUR-SNEDDS resulted in a better stability and release profile than free CUR under simulated ocular conditions. In vitro analysis of mucoadhesive properties revealed that CUR-SNEDDS, modified with a cationic lipid, demonstrated enhanced interactions with mucin, indicating the potential for improved ocular retention. Cytotoxicity tests demonstrated that CUR-SNEDDS did not affect the viability of human corneal epithelial (HCE) cells up to concentrations of 3 μM and displayed superior antioxidant activity compared to free CUR in an oxidative stress model using retinal pigment epithelial (ARPE-19) cells exposed to hydroquinone (HQ). Cell uptake studies confirmed an enhanced accumulation of CUR within the retinal cells following exposure to CUR-SNEDDS compared to neat CUR. CUR-SNEDDS, at lower concentrations, were found to effectively induce SIRT1 expression. Conclusions: The cytocompatibility, antioxidant properties, and enhanced cellular uptake suggest that these developed systems hold promise as formulations for the delivery of CUR to the retina. Full article

Background: Methotrexate (MTX), a folic acid antagonist used in chemotherapy, faces limitations due to cancer cell resistance, high toxicity, and low bioavailability. Objective: This study developed nanoparticles (NPs) of chitosan (QS) and hydroxypropylmethylcellulose phthalate (HPMCP) to encapsulate MTX for potential effect investigation on glioblastoma cell targeting and P-gp efflux inhibition. Method: NPs were produced by the polyelectrolyte complexation method and were characterized by DLS, PDI, DSC, FTIR, PXRD, MEV, drug release profile, and an in vitro mucoadhesion test. Cell viability, flow cytometry, and LSCM using U251MG (glioblastoma) and CCD 1059Sk (fibroblasts) cells were used to evaluate glioblastoma and the P-gp efflux effect. Results: NPPM29 (QS3:1) showed 91.72% encapsulation efficiency, a mean diameter of 452.6 nm, and a zeta potential of +22.5 mV. DSC, FTIR, and PXRD confirmed the QS-HPMCP supramolecular interaction. Liquid falling mucoadhesion tests demonstrated strong retention of NPPM29 (84%) compared to free MTX (10.5%). In vitro release studies indicated controlled drug release at pH 7.4. Cytotoxicity assays in U251MG revealed enhanced efficacy of NPPM29 (IC₅₀ = 68.79 µg/mL) compared to free MTX (IC₅₀ = 80.54 µg/mL), with minimal impact on fibroblasts, confirming tumor specificity. Flow cytometry and LSCM confirmed improved cellular internalization and P-gp inhibition. Conclusions: These findings highlight the potential of MTX-QS-HPMCP-NPs for glioblastoma therapy. Full article

Background: Silibinin (SLB), a flavonoid derived from milk thistle, exhibits promising therapeutic properties but faces significant clinical limitations due to poor solubility and bioavailability. Objectives: This study focuses on the development and characterization of SLB-loaded nanoemulsions designed for mucosal delivery. Methods: Nanoemulsions were prepared using the spontaneous emulsification method, guided by pseudoternary phase diagrams to determine selected component ratios. Comprehensive characterization included particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, rheological properties, and surface tension. Mucoadhesive properties were evaluated using quartz crystal microbalance with dissipation (QCM-D) to quantify interactions with mucin layers. Results: The combination of Capryol 90, Tween 80, and Transcutol in selected proportions yielded nanoemulsions with excellent stability and solubilization capacity, enhancing the solubility of silibinin by 625 times compared to its intrinsic solubility in water. The ternary phase diagram indicated that achieving nanoemulsions with particle sizes between 100 and 300 nm required higher concentrations of surfactants (60%), relative to oil (20%) and water (20%), with formulations predominantly composed of Smix (surfactant and cosurfactant mixture in a 1:1 ratio). Rheological analysis revealed Newtonian behavior, characterized by constant viscosity across varying shear rates and a linear torque response, ensuring ease of application and mechanical stability. QCM-D analysis confirmed strong mucoadhesive interactions, with significant frequency and dissipation shifts, indicative of prolonged retention and enhanced mucosal drug delivery. Furthermore, contact angle measurements showed a marked reduction in surface tension upon interaction with mucin, with the SLB-loaded nanoemulsion demonstrating superior wettability and strong mucoadhesive potential. Conclusions: These findings underscore the suitability of SLB-loaded nanoemulsions as a robust platform for effective mucosal drug delivery, addressing solubility and bioavailability challenges while enabling prolonged retention and controlled therapeutic release. Full article

Chitosan is a positively charged natural polymer with several properties conducive to wound-healing applications, such as biodegradability, structural integrity, hydrophilicity, adhesiveness to tissue, and bacteriostatic potential. Along with other mechanical properties, some of the properties discussed in this review are antibacterial properties, mucoadhesive properties, biocompatibility, high fluid absorption capacity, and anti-inflammatory response. Chitosan forms stable complexes with oppositely charged polymers, arising from electrostatic interactions between (+) amino groups of chitosan and (−) groups of other polymers. These polyelectrolyte complexes (PECs) can be manufactured using various materials and methods, which brings a diversity of formulations and properties that can be optimized for specific wound healing as well as other applications. For example, chitosan-based PEC can be made into dressings/films, hydrogels, and membranes. There are various pros and cons associated with manufacturing the dressings; for instance, a layer-by-layer casting technique can optimize the nanoparticle release and affect the mechanical strength due to the formation of a heterostructure. Furthermore, chitosan’s molecular weight and degree of deacetylation, as well as the nature of the negatively charged biomaterial with which it is cross-linked, are major factors that govern the mechanical properties and biodegradation kinetics of the PEC dressing. The use of chitosan in wound care products is forecasted to drive the growth of the global chitosan market, which is expected to increase by approximately 14.3% within the next decade. This growth is driven by products such as chitoderm-containing ointments, which provide scaffolding for skin cell regeneration. Despite significant advancements, there remains a critical gap in translating chitosan-based biomaterials from research to clinical applications. Full article

Cellulose nanofibers gained increasing interest in the production of medical devices such as mucoadhesive nanohydrogels due to their ability to retain moisture (high hydrophilicity), flexibility, superior porosity and durability, biodegradability, non-toxicity, and biocompatibility. In this work, we aimed to compare the suitability of selected bacterial and vegetal nanocellulose to form hydrogels for biomedical applications. The vegetal and bacterial cellulose nanofibers were synthesized from brewer’s spent grains (BSG) and kombucha membranes, respectively. Two hydrogels were prepared, one based on the vegetal and the other based on the bacterial cellulose nanofibers (VNC and BNC, respectively). VNC was less opaque and more fluid than BNC. The cytocompatibility and in vitro antioxidant activity of the nanocellulose-based hydrogels were investigated using human gingival fibroblasts (HGF-1, ATCC CRL-2014). The investigation of the hydrogel–mucin interaction revealed that the BNC hydrogel had an approx. 2× higher mucin binding efficiency than the VNC hydrogel at a hydrogel/mucin ratio (mg/mg) = 4. The BNC hydrogel exhibited the highest potential to increase the number of metabolically active viable cells (107.60 ± 0.98% of cytotoxicity negative control) among all culture conditions. VNC reduced the amount of reactive oxygen species (ROS) by about 23% (105.5 ± 2.2% of C−) in comparison with the positive control, whereas the ROS level was slightly higher (120.2 ± 3.9% of C−) following the BNC hydrogel treatment. Neither of the two hydrogels showed antibacterial activity when assessed by the diffusion method. The data suggest that the BNC hydrogel based on nanocellulose from kombucha fermentation could be a better candidate for cytocompatible and mucoadhesive nanoformulations than the VNC hydrogel based on nanocellulose from brewer’s spent grains. The antioxidant and antibacterial activity of BNC and both BNC and VNC, respectively, should be improved. Full article

Intravaginal drug administration offers several advantages over other routes, primarily bypassing the initial stages of metabolism. Additionally, this route has demonstrated both local and systemic effects. Mucoadhesive polymeric systems can be utilized to prevent dose loss due to the mucous barriers and the formation of wet cavities. This study employed various techniques to evaluate the performance and characteristics of a mucoadhesive film composed of HPMC-PEG 400 containing retinyl palmitate and ketorolac molecules. Scanning Electron Microscopy (SEM) was employed to analyze the porous structure of the film. Thermogravimetric Analysis (TGA) was conducted at different temperatures to assess thermal stability. Fourier Transform Infrared Spectroscopy (FTIR) was used to analyze the functional groups and intermolecular interactions between the film and the drug. Swelling and weight loss tests indicated that the film disintegrated within 3–4 days. UV-VIS spectroscopy was used for drug release evaluation based on the Higuchi equation. Additionally, the surface wetting properties were assessed through contact angle measurements. The system’s biocompatibility was confirmed using the MTT assay. Finally, adhesion and glide tests demonstrated the film’s interaction with porcine uterine tissue. This study shows that the HPMC-PEG 400 film containing retinyl palmitate molecules interacts effectively with tissue and could be considered a novel tool for treating damaged epithelial tissues. Full article

Tamarind seed polysaccharide (TSP) is a neutral water-soluble galactoxyloglucan isolated from the seed kernel of Tamarindus indica with average molecular weight (Mw) 600–800 kDa. The high viscosity of TSP slows solubilisation, and the absence of charged substituent hinders the formation of electrostatic interactions with biomolecules. TSP was sulphated in a one-step process using dimethylformamide as a solvent, and sulphur trioxide-pyridine complex as a sulphating reagent. Studies of chemical structure, molecular weight distribution and viscosity were conducted to characterise the synthesised products. The sulphation degree was established by conductimetric titration; the sulphate group distribution was studied by NMR spectroscopy and liquid chromatography-mass spectrometry, and sulphated TSP oligomers were obtained by enzymatic degradation with cellulase and/or xyloglucanase. Sulphated products showed higher solubility than TSP, Mws in the range of 700–1000 kDa, a sulphation degree of two to four per subunit and pseudoplastic behaviour. A preliminary study of mucoadhesion revealed the unexpected interaction of S-TSP with mucin, providing a route by which sulphated TSP interactions with biomolecules may be influenced. Full article

Background/Objectives: Due to the high frequency and severity of upper respiratory bacterial infections, probiotics could offer a new medical approach. We explored the antibacterial and anti-inflammatory properties of the new strain Lactiplantibacillus plantarum BIA and formulated a nasal spray. Methods: L. plantarum BIA was isolated from orange peel and taxonomically identified through 16S rRNA gene sequencing. Its antibacterial activity was tested against Pseudomonas aeruginosa, Streptococcus pyogenes, Bacillus subtilis, Escherichia coli, and Staphylococcus aureus, while anti-inflammatory potential was evaluated by Griess assay. BIA genome was fully sequenced and analyzed to assess its safety. BIA was formulated in a freeze-dried matrix, containing prebiotics and cryoprotectants, to be reconstituted with a polymer solution. Solutions containing two types of hydroxypropyl methylcellulose (HPMC) and hyaluronic acid were evaluated as resuspending media and compared in terms of pH, viscosity, and mucoadhesion ability. The biological activity of BIA formulated as nasal spray was verified together with the stability of the selected formulations. Results: L. plantarum BIA inhibited human pathogens’ growth and showed anti-inflammatory activity and a safe profile. In the best-performing formulation, the probiotic is lyophilized in 10% fructooligosaccharides, 0.1% ascorbic acid, and 0.5% lactose and reconstituted with HPMC high viscosity 1% w/v. This composition ensured the probiotic’s viability for up to six months in its dried form and one week after reconstitution. It also allowed interaction with the nasal mucosa, preserving its antimicrobial and anti-inflammatory activities. Conclusion: The developed nasal spray could become a promising formulation in the field of nasal infectious and inflammatory diseases. Full article

Pathogen infections constitute a serious problem in the field of lung diseases, especially in severe conditions such as chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS). Exacerbations of COPD and ARDS can be significantly influenced by bacterial infections from Pseudomonas aeruginosa and Staphylococcus aureus, which can hasten the decline of lung function. Moreover, the abuse of high-dose antibiotics used to treat obstinate infections is contributing to the growing issue of multidrug resistance (MDR) by microorganisms. Currently, new therapeutic strategies capable of surprising and fighting pathogens with new modalities are missing. In this framework, bio-composite nanogels (NGs) based on natural polymers with intrinsic antimicrobial properties such as chitosan (CS) and hyaluronic acid (HA) have been developed for the treatment of lung infections. The DLS and TEM results showed that NGs have a spherical shape with a size smaller than 100 nm, making it possible for them to potentially reach the lung site and evade the clearance of alveolar macrophages. FTIR spectra demonstrated that only electrostatic interactions, not chemical reactions, occur between NG precursors. Rheological analysis highlighted NGs’ injectability and mucoadhesive capacity. Moreover, an MTT assay on human lung fibroblast cells for biocompatibility evaluation showed good viability up to 48 h. Finally, an antimicrobial test on P. aeruginosa and S. aureus showed an increase in antimicrobial activity as the NG concentration increases, with a reduction in bacterial growth of around 60% at 375 μg/mL. Full article

Background/Objectives: For locally applied, locally acting generic drug products, comparison to an originator product based on systemic exposure is usually not feasible due to low plasma concentrations and inadequate reflection of local exposure at the site of action. Where a validated PD model exists, a comparative clinical study can be performed in healthy subjects; where no surrogate endpoint is available, patients with the relevant indication need to be enrolled, with all the associated factors which could result in lack of sensitivity. Even though the need for alternative in vitro approaches has been acknowledged by both industry and regulatory bodies, the complexity of in vivo drug delivery processes makes the development of guidance documents particularly difficult. Our objective was to present in vitro approaches less classically used and to address in vivo relevance of the selected tests. Methods: This article analyses current regulatory approaches in Europe and the U.S., and highlights the key advantages of in vitro tests in terms of their sensitivity, reliability, reproducibility and in vivo relevance using locally applied flurbiprofen in various formulations. Results: The in vitro esophageal retention (IVOR) model demonstrates that the first 6–10 min after application of different flurbiprofen formulations is important for their comparison and also offers the best correlation with in vivo data using the partial area under the concentration-time curves (pAUCs). Rheological evaluations further demonstrated that the mucoadhesive properties of the gel spray formulation are based on interaction with mucin. Conclusions: Designing a relevant in vitro test requires adequate evaluation of the complexity of the drug substance, drug product, dosing conditions and delivery processes. Full article