Special Issue "Pharmaceutical Particulates and Membranes for Delivery of Drugs and Bioactive Molecules"

A special issue of Pharmaceutics (ISSN 1999-4923).

Deadline for manuscript submissions: closed (30 September 2019).

Special Issue Editors

Dr. Diganta B. Das
E-Mail Website
Guest Editor
Department of Chemical Engineering, Loughborough University, Loughborough LE11 3TU, UK
Fax: 0044 1509 223923
Interests: membrane fabrication; particulate drug delivery; microneedle drug delivery; biomolecular separation
Special Issues and Collections in MDPI journals
Prof. G Arthanareeswaran
E-Mail Website
Guest Editor
Department of Chemical Engineering, National Institute of Technology, Tiruchirappalli, 620015, India
Interests: polymer membrane; membrane modification; biomolecule separation
Dr. Mostafa Mabrouk
E-Mail
Guest Editor
Refractories, Ceramics and Building materials Department, (Biomaterials group),, National Research Centre, 33El Bohouth St. (former EL Tahrir St.), Dokki, Giza P.O. 12622, Egypt
Interests: drug delivery systems; biomaterials; tissue engineering; nanomaterials; hydrogels
Prof. Hanan H. Beherei
E-Mail
Guest Editor
Ceramics Department, (Biomaterials group) National Research Centre, 33El Bohouth St.(former EL Tahrir St.), Dokki, Giza P.O. 12622, Egypt
Interests: bioceramics; biopolymers; biocomposites; nanomaterials; biochemical engineering; tissue engineering and drug delivery

Special Issue Information

Dear Colleagues,

We would like to invite you to contribute to this Special Issue, entitled "Pharmaceutical Particulates and Membranes for Delivery of Drugs and Bioactive Molecules".

A drug release profile is a consequential factor for nanoparticle application, directly related to drug stability and therapeutic results, as well as formulation development. Pharmaceutical particulates of different sizes and shapes (e.g., liposomes, oil-in-water emulsions, polymeric nano- and microspheres, metallic nanoparticles (NPs), such as gold, silver, and iron oxide crystals, core-shell hybrid NPs) offer many diagnostic and therapeutic applications. Membranes are also extensively utilized in many applications. They are very beneficial, especially for the distribution of macromolecular drugs and biopharmaceutical drugs (peptides, proteins, antibodies, oligonucleotides, plasmids, and viruses) with physicochemically and pharmacokinetically vulnerable.

Delivery of drugs and bioactive molecules using particulates and membranes has gained a great deal of attention for various applications, such as the treatment of secondary infections, cancer treatment, skin regeneration and orthopaedic applications, antimicrobial drug delivery, and others. In addition, several production techniques have been utilized for the fabrication of particulates and membranes in the last decade, which include lyophilization, micro-emulsion, nano-spray dryer, nano-electrospinning, slip casting and 3D printers. Therefore, pharmaceutical particulates and membranes possess excellent prospects to deliver drugs and bioactive molecules with the potential to improve new delivering strategies like sustained and controlled release.

 Taking these into consideration, this Special Issue invites articles dealing with the following topics:

1- Particulates preparation techniques (nano- to micron- scale particulates)

2- Membranes fabrication techniques (e.g., nano-electro spinner, slip casting, 3D printers).

3- In vitro and in vivo studies of pharmaceutical particulates or membranes.

4- Modelling and optimization of drug release from pharmaceutical particulates or membranes

 If sufficient numbers of papers are published in the planned Special Issue (≥10), then we will also compile an edited book containing the papers.

We look forward to receiving your contributions.

Sincerely,

Dr. Diganta B. Das
Prof. G Arthanareeswaran
Dr. Mostafa Mabrouk
Prof. Hanan H. Beherei
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Nanoparticles, drug delivery, cancer therapy, microspheres, self-assemblies
  • Polymers, copolymers, biomaterials, microparticle, nanoparticle,
  • Pharmaceutical dosage forms, molecular drugs, targeted drug delivery
  • Brain diseases, targeting, nanocarriers
  • Intracellular drug delivery, gene transfection, controlled release
  • Morphology control, nanoparticle endocytosis, biocompatibility

Published Papers (10 papers)

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Research

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Open AccessArticle
Evaluation of Drug Delivery and Efficacy of Ciprofloxacin-Loaded Povidone Foils and Nanofiber Mats in a Wound-Infection Model Based on Ex Vivo Human Skin
Pharmaceutics 2019, 11(10), 527; https://doi.org/10.3390/pharmaceutics11100527 - 12 Oct 2019
Abstract
Topical treatment of wound infections is often a challenge due to limited drug availability at the site of infection. Topical drug delivery is an attractive option for reducing systemic side effects, provided that a more selective and sustained local drug delivery is achieved. [...] Read more.
Topical treatment of wound infections is often a challenge due to limited drug availability at the site of infection. Topical drug delivery is an attractive option for reducing systemic side effects, provided that a more selective and sustained local drug delivery is achieved. In this study, a poorly water-soluble antibiotic, ciprofloxacin, was loaded on polyvinylpyrrolidone (PVP)-based foils and nanofiber mats using acetic acid as a solubilizer. Drug delivery kinetics, local toxicity, and antimicrobial activity were tested on an ex vivo wound model based on full-thickness human skin. Wounds of 5 mm in diameter were created on 1.5 × 1.5 cm skin blocks and treated with the investigated materials. While nanofiber mats reached the highest amount of delivered drug after 6 h, foils rapidly achieved a maximum drug concentration and maintained it over 24 h. The treatment had no effect on the overall skin metabolic activity but influenced the wound healing process, as observed using histological analysis. Both delivery systems were efficient in preventing the growth of Pseudomonas aeruginosa biofilms in ex vivo human skin. Interestingly, foils loaded with 500 µg of ciprofloxacin accomplished the complete eradication of biofilm infections with 1 × 109 bacteria/wound. We conclude that antimicrobial-loaded resorbable PVP foils and nanofiber mats are promising delivery systems for the prevention or topical treatment of infected wounds. Full article
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Open AccessArticle
Development and Evaluation of Alginate Membranes with Curcumin-Loaded Nanoparticles for Potential Wound-Healing Applications
Pharmaceutics 2019, 11(8), 389; https://doi.org/10.3390/pharmaceutics11080389 - 03 Aug 2019
Abstract
Non-biodegradable materials with a low swelling capacity and which are opaque and occlusive are the main problems associated with the clinical performance of some commercially available wound dressings. In this work, a novel biodegradable wound dressing was developed by means of alginate membrane [...] Read more.
Non-biodegradable materials with a low swelling capacity and which are opaque and occlusive are the main problems associated with the clinical performance of some commercially available wound dressings. In this work, a novel biodegradable wound dressing was developed by means of alginate membrane and polycaprolactone nanoparticles loaded with curcumin for potential use in wound healing. Curcumin was employed as a model drug due to its important properties in wound healing, including antimicrobial, antifungal, and anti-inflammatory effects. To determine the potential use of wound dressing, in vitro, ex vivo, and in vivo studies were carried out. The novel membrane exhibited the diverse functional characteristics required to perform as a substitute for synthetic skin, such as a high capacity for swelling and adherence to the skin, evidence of pores to regulate the loss of transepidermal water, transparency for monitoring the wound, and drug-controlled release by the incorporation of nanoparticles. The incorporation of the nanocarriers aids the drug in permeating into different skin layers, solving the solubility problems of curcumin. The clinical application of this system would cover extensive areas of mixed first- and second-degree wounds, without the need for removal, thus decreasing the patient’s discomfort and the risk of altering the formation of the new epithelium. Full article
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Open AccessArticle
Entrapment of N-Hydroxyphthalimide Carbon Dots in Different Topical Gel Formulations: New Composites with Anticancer Activity
Pharmaceutics 2019, 11(7), 303; https://doi.org/10.3390/pharmaceutics11070303 - 01 Jul 2019
Abstract
In the present study, the antitumoral potential of three gel formulations loaded with carbon dots prepared from N-hydroxyphthalimide (CD-NHF) was examined and the influence of the gels on two types of skin melanoma cell lines and two types of breast cancer cell [...] Read more.
In the present study, the antitumoral potential of three gel formulations loaded with carbon dots prepared from N-hydroxyphthalimide (CD-NHF) was examined and the influence of the gels on two types of skin melanoma cell lines and two types of breast cancer cell lines in 2D (cultured cells in normal plastic plates) and 3D (Matrigel) models was investigated. Antitumoral gels based on sodium alginate (AS), carboxymethyl cellulose (CMC), and the carbomer Ultrez 10 (CARB) loaded with CD-NHF were developed according to an adapted method reported by Hellerbach. Viscoelastic properties of CD-NHF-loaded gels were analyzed by rheological analysis. Also, for both CD-NHF and CD-NHF-loaded gels, the fluorescence properties were analyzed. Cell proliferation, apoptosis, and mitochondrial activity were analyzed according to basic methods used to evaluate modulatory activities of putative anticancer agents, which include reference cancer cell line culture assays in both classic 2D and 3D cultures. Using the rheological measurements, the mechanical properties of gel formulations were analyzed; all samples presented gel-like rheological characteristics. The presence of CD-NHF within the gels induces a slight decrease of the dynamic moduli, indicating a flexible gel structure. The fluorescence investigations showed that for the gel-loaded CD-NHF, the most intense emission peak was located at 370 nm (upon excitation at 330 nm). 3D cell cultures displayed visibly larger structure of tumor cells with less active phenotype appearance. The in vitro results for tested CD-NHF-loaded gel formulations revealed that the new composites are able to affect the number, size, and cellular organization of spheroids and impact individual tumor cell ability to proliferate and aggregate in spheroids. Full article
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Open AccessCommunication
Enhancement of Magnetic Hyperthermia by Mixing Synthetic Inorganic and Biomimetic Magnetic Nanoparticles
Pharmaceutics 2019, 11(6), 273; https://doi.org/10.3390/pharmaceutics11060273 - 11 Jun 2019
Abstract
In this work we report on the synthesis and characterization of magnetic nanoparticles of two distinct origins, one inorganic (MNPs) and the other biomimetic (BMNPs), the latter based on a process of bacterial synthesis. Each of these two kinds of particles has its [...] Read more.
In this work we report on the synthesis and characterization of magnetic nanoparticles of two distinct origins, one inorganic (MNPs) and the other biomimetic (BMNPs), the latter based on a process of bacterial synthesis. Each of these two kinds of particles has its own advantages when used separately with biomedical purposes. Thus, BMNPs present an isoelectric point below neutrality (around pH 4.4), while MNPs show a zero-zeta potential at pH 7, and appear to be excellent agents for magnetic hyperthermia. This means that the biomimetic particles are better suited to be loaded with drug molecules positively charged at neutral pH (notably, doxorubicin, for instance) and releasing it at the acidic tumor environment. In turn, MNPs may provide their transport capabilities under a magnetic field. In this study it is proposed to use a mixture of both kinds of particles at two different concentrations, trying to get the best from each of them. We study which mixture performs better from different points of view, like stability and magnetic hyperthermia response, while keeping suitable drug transport capabilities. This composite system is proposed as a close to ideal drug vehicle with added enhanced hyperthermia response. Full article
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Open AccessArticle
Development and In Vitro-In Vivo Evaluation of a Novel Sustained-Release Loxoprofen Pellet with Double Coating Layer
Pharmaceutics 2019, 11(6), 260; https://doi.org/10.3390/pharmaceutics11060260 - 05 Jun 2019
Abstract
This study aimed to develop a novel sustained release pellet of loxoprofen sodium (LXP) by coating a dissolution-rate controlling sub-layer containing hydroxypropyl methyl cellulose (HPMC) and citric acid, and a second diffusion-rate controlling layer containing aqueous dispersion of ethyl cellulose (ADEC) on the [...] Read more.
This study aimed to develop a novel sustained release pellet of loxoprofen sodium (LXP) by coating a dissolution-rate controlling sub-layer containing hydroxypropyl methyl cellulose (HPMC) and citric acid, and a second diffusion-rate controlling layer containing aqueous dispersion of ethyl cellulose (ADEC) on the surface of a LXP conventional pellet, and to compare its performance in vivo with an immediate release tablet (Loxinon®). A three-level, three-factor Box-Behnken design and the response surface model (RSM) were used to investigate and optimize the effects of the citric acid content in the sub-layer, the sub-layer coating level, and the outer ADEC coating level on the in vitro release profiles of LXP sustained release pellets. The pharmacokinetic studies of the optimal sustained release pellets were performed in fasted beagle dogs using an immediate release tablet as a reference. The results illustrated that both the citric acid (CA) and ADEC as the dissolution- and diffusion-rate controlling materials significantly decreased the drug release rate. The optimal formulation showed a pH-independent drug release in media at pH above 4.5 and a slightly slow release in acid medium. The pharmacokinetic studies revealed that a more stable and prolonged plasma drug concentration profile of the optimal pellets was achieved, with a relative bioavaibility of 87.16% compared with the conventional tablets. This article provided a novel concept of two-step control of the release rate of LXP, which showed a sustained release both in vitro and in vivo. Full article
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Open AccessArticle
Nanoemulsion Based Vehicle for Effective Ocular Delivery of Moxifloxacin Using Experimental Design and Pharmacokinetic Study in Rabbits
Pharmaceutics 2019, 11(5), 230; https://doi.org/10.3390/pharmaceutics11050230 - 11 May 2019
Abstract
Nanoemulsion is one of the potential drug delivery strategies used in topical ocular therapy. The purpose of this study was to design and optimize a nanoemulsion-based system to improve therapeutic efficacy of moxifloxacin in ophthalmic delivery. Moxifloxacin nanoemulsions were prepared by testing their [...] Read more.
Nanoemulsion is one of the potential drug delivery strategies used in topical ocular therapy. The purpose of this study was to design and optimize a nanoemulsion-based system to improve therapeutic efficacy of moxifloxacin in ophthalmic delivery. Moxifloxacin nanoemulsions were prepared by testing their solubility in oil, surfactants, and cosurfactants. A pseudoternary phase diagram was constructed by titration technique and nanoemulsions were obtained with four component mixtures of Tween 80, Soluphor® P, ethyl oleate and water. An experiment with simplex lattice design was conducted to assess the influence of formulation parameters in seven nanoemulsion formulations (MM1–MM7) containing moxifloxacin. Physicochemical characteristics and in vitro release of MM1–MM7 were examined and optimized formulation (MM3) was further evaluated for ex vivo permeation, antimicrobial activity, ocular irritation and stability. Drug pharmacokinetics in rabbit aqueous humor was assessed for MM3 and compared with conventional commercial eye drop formulation (control). MM3 exhibited complete drug release in 3 h by Higuchi diffusion controlled mechanism. Corneal steady state flux of MM3 (~32.01 µg/cm2/h) and control (~31.53 µg/cm2/h) were comparable. Ocular irritation study indicated good tolerance of MM3 and its safety for ophthalmic use. No significant changes were observed in the physicochemical properties of MM3 when stored in the refrigerator for 3 months. The greater aqueous humor concentration (Cmax; 555.73 ± 133.34 ng/mL) and delayed Tmax value (2 h) observed in MM3 suggest a reduced dosing frequency and increased therapeutic efficacy relative to control. The area under the aqueous humor concentration versus time curve (AUC0–8 h) of MM3 (1859.76 ± 424.51 ng·h/mL) was ~2 fold higher (p < 0.0005) than the control, suggesting a significant improvement in aqueous humor bioavailability. Our findings suggest that optimized nanoemulsion (MM3) enhanced the therapeutic effect of moxifloxacin and can therefore be used as a safe and effective delivery vehicle for ophthalmic therapy. Full article
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Open AccessArticle
The Process–Property–Performance Relationship of Medicated Nanoparticles Prepared by Modified Coaxial Electrospraying
Pharmaceutics 2019, 11(5), 226; https://doi.org/10.3390/pharmaceutics11050226 - 10 May 2019
Cited by 6
Abstract
In pharmaceutical nanotechnology, the intentional manipulation of working processes to fabricate nanoproducts with suitable properties for achieving the desired functional performances is highly sought after. The following paper aims to detail how a modified coaxial electrospraying has been developed to create ibuprofen-loaded hydroxypropyl [...] Read more.
In pharmaceutical nanotechnology, the intentional manipulation of working processes to fabricate nanoproducts with suitable properties for achieving the desired functional performances is highly sought after. The following paper aims to detail how a modified coaxial electrospraying has been developed to create ibuprofen-loaded hydroxypropyl methylcellulose nanoparticles for improving the drug dissolution rate. During the working processes, a key parameter, i.e., the spreading angle of atomization region (θ, °), could provide a linkage among the working process, the property of generated nanoparticles and their functional performance. Compared with the applied voltage (V, kV; D = 2713 − 82V with RθV2 = 0.9623), θ could provide a better correlation with the diameter of resultant nanoparticles (D, nm; D = 1096 − 5θ with R2 = 0.9905), suggesting a usefulness of accurately predicting the nanoparticle diameter. The drug released from the electrosprayed nanoparticles involved both erosion and diffusion mechanisms. A univariate quadratic equation between the time of releasing 95% of the loaded drug (t, min) and D (t = 38.7 + 0.097D − 4.838 × 105D2 with a R2 value of 0.9976) suggests that the nanoparticle diameter has a profound influence on the drug release performance. The clear process-property-performance relationship should be useful for optimizing the electrospraying process, and in turn for achieving the desired medicated nanoparticles. Full article
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Open AccessArticle
Cell Internalization in Fluidic Culture Conditions Is Improved When Microparticles Are Specifically Targeted to the Human Epidermal Growth Factor Receptor 2 (HER2)
Pharmaceutics 2019, 11(4), 177; https://doi.org/10.3390/pharmaceutics11040177 - 11 Apr 2019
Abstract
Purpose: To determine if the specific targeting of microparticles improves their internalization by cells under fluidic conditions. Methods: Two isogenic breast epithelial cell lines, one overexpressing the Human Epidermal Growth Factor Receptor 2 (HER2) oncogene (D492HER2) and highly tumorigenic and the other expressing [...] Read more.
Purpose: To determine if the specific targeting of microparticles improves their internalization by cells under fluidic conditions. Methods: Two isogenic breast epithelial cell lines, one overexpressing the Human Epidermal Growth Factor Receptor 2 (HER2) oncogene (D492HER2) and highly tumorigenic and the other expressing HER2 at much lower levels and non-tumorigenic (D492), were cultured in the presence of polystyrene microparticles of 1 µm in diameter, biofunctionalized with either a specific anti-HER2 antibody or a non-specific secondary antibody. Mono- and cocultures of both cell lines in static and fluidic conditions were performed, and the cells with internalized microparticles were scored. Results: Globally, the D492 cell line showed a higher endocytic capacity than the D492HER2 cell line. Microparticles that were functionalized with the anti-HER2 antibody were internalized by a higher percentage of cells than microparticles functionalized with the non-specific secondary antibody. Although internalization was reduced in fluidic culture conditions in comparison with static conditions, the increase in the internalization of microparticles biofunctionalized with the anti-HER2 antibody was higher for the cell line overexpressing HER2. Conclusion: The biofunctionalization of microparticles with a specific targeting molecule remarkably increases their internalization by cells in fluidic culture conditions (simulating the blood stream). This result emphasizes the importance of targeting for future in vivo delivery of drugs and bioactive molecules through microparticles. Full article
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Open AccessArticle
In Vitro and In Silico Analyses of Nicotine Release from a Gelisphere-Loaded Compressed Polymeric Matrix for Potential Parkinson’s Disease Interventions
Pharmaceutics 2018, 10(4), 233; https://doi.org/10.3390/pharmaceutics10040233 - 15 Nov 2018
Cited by 1
Abstract
This study aimed to develop a prolonged-release device for the potential site-specific delivery of a neuroprotective agent (nicotine). The device was formulated as a novel reinforced crosslinked composite polymeric system with the potential for intrastriatal implantation in Parkinson’s disease interventions. Polymers with biocompatible [...] Read more.
This study aimed to develop a prolonged-release device for the potential site-specific delivery of a neuroprotective agent (nicotine). The device was formulated as a novel reinforced crosslinked composite polymeric system with the potential for intrastriatal implantation in Parkinson’s disease interventions. Polymers with biocompatible and bioerodible characteristics were selected to incorporate nicotine within electrolyte-crosslinked alginate-hydroxyethylcellulose gelispheres compressed within a release rate-modulating external polymeric matrix, comprising either hydroxypropylmethylcellulose (HPMC), polyethylene oxide (PEO), or poly(lactic-co-glycolic) acid (PLGA) to prolong nicotine release. The degradation and erosion studies showed that the produced device had desirable robustness with the essential attributes for entrapping drug molecules and retarding their release. Zero-order drug release was observed over 50 days from the device comprising PLGA as the external matrix. Furthermore, the alginate-nicotine interaction, the effects of crosslinking on the alginate-hydroxyethycellulose (HEC) blend, and the effects of blending PLGA, HPMC, and PEO on device performance were mechanistically elucidated using molecular modelling simulations of the 3D structure of the respective molecular complexes to predict the molecular interactions and possible geometrical orientation of the polymer morphologies affecting the geometrical preferences. The compressed polymeric matrices successfully retarded the release of nicotine over several days. PLGA matrices offered minimal rates of matrix degradation and successfully retarded nicotine release, leading to the achieved zero-order release for 50 days following exposure to simulated cerebrospinal fluid (CSF). Full article
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Review

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Open AccessReview
Nanoparticle- and Nanoporous-Membrane-Mediated Delivery of Therapeutics
Pharmaceutics 2019, 11(6), 294; https://doi.org/10.3390/pharmaceutics11060294 - 21 Jun 2019
Abstract
Pharmaceutical particulates and membranes possess promising prospects for delivering drugs and bioactive molecules with the potential to improve drug delivery strategies like sustained and controlled release. For example, inorganic-based nanoparticles such as silica-, titanium-, zirconia-, calcium-, and carbon-based nanomaterials with dimensions smaller than [...] Read more.
Pharmaceutical particulates and membranes possess promising prospects for delivering drugs and bioactive molecules with the potential to improve drug delivery strategies like sustained and controlled release. For example, inorganic-based nanoparticles such as silica-, titanium-, zirconia-, calcium-, and carbon-based nanomaterials with dimensions smaller than 100 nm have been extensively developed for biomedical applications. Furthermore, inorganic nanoparticles possess magnetic, optical, and electrical properties, which make them suitable for various therapeutic applications including targeting, diagnosis, and drug delivery. Their properties may also be tuned by controlling different parameters, e.g., particle size, shape, surface functionalization, and interactions among them. In a similar fashion, membranes have several functions which are useful in sensing, sorting, imaging, separating, and releasing bioactive or drug molecules. Engineered membranes have been developed for their usage in controlled drug delivery devices. The latest advancement in the technology is therefore made possible to regulate the physico-chemical properties of the membrane pores, which enables the control of drug delivery. The current review aims to highlight the role of both pharmaceutical particulates and membranes over the last fifteen years based on their preparation method, size, shape, surface functionalization, and drug delivery potential. Full article
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