Special Issue "Innovative Drug Delivery Platforms: From Natural to Engineered Materials"

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

Deadline for manuscript submissions: closed (31 January 2020).

Special Issue Editor

Prof. Dr. Anton Ficai
Website
Guest Editor
1. Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University POLITEHNICA of Bucharest, 1-7 Gh. Polizu st., 011061 Bucharest, Romania
2. Academy of Romanian Scientists, 54 Splaiul Independenței st., Bucharest, Romania
Interests: bio(nano)materials; synthesis methods; materials processing and design; advanced coatings; tissue engineering; drug delivery; characterization methods
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Special Issue Information

Dear Colleagues,

The innovations in Drug Delivery Systems are strongly associated with the development of new support materials as well as their functionalization in order to assure targeting, internalization, tuned delivery rate and profile, etc. This Special Issue focuses on multifunctional, smart drug delivery systems for diagnosis and treatment of cancer, infections, and diabetes, but any other topics are welcome. Regarding desired support materials, we are especially looking for natural and synthetic polymers, carbonaceous materials (single and multiwalled carbon nanotubes, fullerenes, graphene and graphene oxide, etc.), oxides (including micro and mesoporous materials), metal nanoparticles (silver, gold, etc.), and composite materials. The mechanism of delivery can be mainly based on diffusion, swelling, or chemical reaction; can be triggered by any factors such as temperature, pH, enzymes, or different external factors such as light, alternating electromagnetic fields, etc.; and can be resorbable or non-resorbable supports, etc. Additionally, manuscripts devoted to the study of the potential, short, mid-, and long-term efficiency and toxicity related to the use of drug delivery systems are welcome.

Prof. Anton Ficai
Guest Editor

Manuscript Submission Information

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Keywords

  • Drug-delivery platforms
  • Mechanisms of delivery
  • Natural and synthetic materials in drug delivery
  • Treatment of cancer, infections, diabetes, etc.
  • Surface functionalization
  • Natural and synthetic biological active agents

Published Papers (8 papers)

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Research

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Open AccessArticle
A Smart Drug Delivery System Based on Biodegradable Chitosan/Poly(allylamine hydrochloride) Blend Films
Pharmaceutics 2020, 12(2), 131; https://doi.org/10.3390/pharmaceutics12020131 - 04 Feb 2020
Cited by 1
Abstract
The amalgamation of natural polysaccharides with synthetic polymers often produces fruitful results in the area of drug delivery due to their biodegradable and biocompatible nature. In this study, a series of blend films composed of chitosan (CS)/poly(allylamine hydrochloride) (PAH) in different compositions were [...] Read more.
The amalgamation of natural polysaccharides with synthetic polymers often produces fruitful results in the area of drug delivery due to their biodegradable and biocompatible nature. In this study, a series of blend films composed of chitosan (CS)/poly(allylamine hydrochloride) (PAH) in different compositions were prepared as smart drug delivery matrices. The properties of these polymeric films were then explored. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) analysis confirmed an intermolecular hydrogen bonding between CS and PAH. Atomic force microscopy (AFM) revealed improvements in surface morphology as the percentage of PAH in the blend films increased up to 60% (w/w). Water contact angle (WCA) ranged between 97° to 115°, exhibiting the hydrophobic nature of the films. Two films were selected, CTH-1 (90% CS and 10% PAH) and CTH-2 (80% CS and 20% PAH), to test for in vitro cumulative drug release (%) at 37 ± 0.5 °C as a function of time. It was revealed that for simulated gastric fluid (SGF) with pH 1.2, the cumulative drug release (CDR) for CTH-1 and CTH-2 was around 88% and 85% in 50 min, respectively. Both films converted into gel-like material after 30 min. On the other hand, in pH 7.4 phosphate buffer saline (PBS) solution, the maximum CDR for CTH-1 and CTH-2 was 93% in 90 min and 98% in 120 min, respectively. After 120 min, these films became fragments. Sustained drug release was observed in PBS, as compared to SGF, because of the poor stability of the films in the latter. These results demonstrate the excellent potential of blend films in sustained-release drug delivery systems for hydrophilic or unstable drugs. Full article
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Open AccessArticle
Metal Organic [email protected] Core/Shell-Structured Nanoplatform for Drug Delivery
Pharmaceutics 2020, 12(2), 98; https://doi.org/10.3390/pharmaceutics12020098 - 25 Jan 2020
Abstract
Modern pharmaceutics requires novel drug loading platforms with high drug loading capacity, controlled release, high stability, and good biocompacity. Metal–organic frameworks (MOFs) show promising applications in biomedicine owing to their extraordinarily high surface area, tunable pore size, and adjustable internal surface properties. However, [...] Read more.
Modern pharmaceutics requires novel drug loading platforms with high drug loading capacity, controlled release, high stability, and good biocompacity. Metal–organic frameworks (MOFs) show promising applications in biomedicine owing to their extraordinarily high surface area, tunable pore size, and adjustable internal surface properties. However, MOFs have low stability due to weak coordinate bonding and limited biocompatibility, limiting their bioapplication. In this study, we fabricated MOFs/polysilsesquioxane (PSQ) nanocomposites and utilized them as drug carriers. Amine-functionalized MOF (UiO-66-NH2) nanoparticles were synthesized and encapsulated with epoxy-functionalized polysilsesquioxane layer on the surface via a facile process. MOFs possessed high surface area and regular micropores, and PSQs offered stability, inertness, and functionality. The obtained UiO-66-NH2@EPSQ nanocomposites were utilized as carriers for ibuprofen, a drug with carboxylic groups on the surface, and demonstrated high drug loading capacity and well-controlled release property. The UiO-66-NH2@EPSQ nanocomposite exhibited low cytotoxicity to HeLa cells within a wide concentration range of 10–100 µg/mL, as estimated by the MTT method. The UiO-66-NH2@EPSQ drug release system could be a potential platform in the field of controlled drug delivery. Full article
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Open AccessArticle
Pectin and Zinc Alginate: The Right Inner/Outer Polymer Combination for Core-Shell Drug Delivery Systems
Pharmaceutics 2020, 12(2), 87; https://doi.org/10.3390/pharmaceutics12020087 - 21 Jan 2020
Cited by 1
Abstract
Core-shell beads loaded with betamethasone were developed using co-axial prilling as production technique and pectin plus alginate as polymeric carriers. During this study, many operative conditions were intensively investigated to find the best ones necessary to produce uniform core-shell particle systems in a [...] Read more.
Core-shell beads loaded with betamethasone were developed using co-axial prilling as production technique and pectin plus alginate as polymeric carriers. During this study, many operative conditions were intensively investigated to find the best ones necessary to produce uniform core-shell particle systems in a reproducible way. Particularly, feed solutions’ composition, polymers mass ratios and the effect of the main process parameters on particles production, micromeritics, inner structure, drug loading and drug-release/swelling profiles in simulated biological fluids were studied. The optimized core-shell formulation F5 produced with a pectin core concentration of 4.0% w/v and an alginate shell concentration of 2.0% w/v (2:1 core:shell ratio) acted as a sustained drug delivery system. It was able to reduce the early release of the drug in the upper part of the gastro-intestinal tract for the presence of the zinc-alginate gastro-resistant outer layer and to specifically deliver it in the colon, thanks to the selectivity of amidated low methoxy pectin core for this district. Therefore, these particles may be proposed as colon targeted drug delivery systems useful for inflammatory bowel disease (IBD) therapy. Full article
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Open AccessArticle
Silica-Polymer Composites as the Novel Antibiotic Delivery Systems for Bone Tissue Infection
Pharmaceutics 2020, 12(1), 28; https://doi.org/10.3390/pharmaceutics12010028 - 30 Dec 2019
Abstract
Bone tissue inflammation, osteomyelitis, is commonly caused by bacterial invasion and requires prolonged antibiotic therapy for weeks or months. Thus, the aim of this study was to develop novel silica-polymer local bone antibiotic delivery systems characterized by a sustained release of ciprofloxacin [...] Read more.
Bone tissue inflammation, osteomyelitis, is commonly caused by bacterial invasion and requires prolonged antibiotic therapy for weeks or months. Thus, the aim of this study was to develop novel silica-polymer local bone antibiotic delivery systems characterized by a sustained release of ciprofloxacin (CIP) which remain active against Staphylococcus aureus for a few weeks, and do not have a toxic effect towards human osteoblasts. Four formulations composed of ethylcellulose (EC), polydimethylsiloxane (PDMS), freeze-dried CIP, and CIP-adsorbed mesoporous silica materials (MCM-41-CIP) were prepared via solvent-evaporation blending method. All obtained composites were characterized in terms of molecular structure, morphological, and structural properties by using Fourier Transform Infrared Spectroscopy (FTIR), scanning electron microscopy equipped with energy-dispersive X-ray spectroscopy (SEM/EDX), and X-ray diffraction (XRD), thermal stability by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC), and in vitro antibiotic release. The antibacterial activity against Staphylococcus aureus (ATCC 6538) as well as the in vitro cytocompatibility to human osteoblasts of obtained composites were also examined. Physicochemical results confirmed the presence of particular components (FTIR), formation of continuous polymer phase onto the surface of freeze-dried CIP or MCM-41-CIP (SEM/EDX), and semi-crystalline (composites containing freeze-dried CIP) or amorphous (composites containing MCM-41-CIP) structure (XRD). TGA and DSC analysis indicated the high thermal stability of CIP adsorbed onto the MCM-41, and higher after MCM-41-CIP coating with polymer blend. The release study revealed the significant reduction in initial burst of CIP for the composites which contained MCM-41-CIP instead of freeze-dried CIP. These composites were also characterized by the 30-day activity against S. aureus and the highest cytocompatibility to human osteoblasts in vitro. Full article
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Open AccessArticle
Nanohydrogels Based on Self-Assembly of Cationic Pullulan and Anionic Dextran Derivatives for Efficient Delivery of Piroxicam
Pharmaceutics 2019, 11(12), 622; https://doi.org/10.3390/pharmaceutics11120622 - 21 Nov 2019
Abstract
A cationic derivative of pullulan was obtained by grafting reaction and used together with dextran sulfate to form polysaccharide-based nanohydrogel cross-linked via electrostatic interactions between polyions. Due to the polycation-polyanion interactions nanohydrogel particles were formed instantly and spontaneously in water. The nanoparticles were [...] Read more.
A cationic derivative of pullulan was obtained by grafting reaction and used together with dextran sulfate to form polysaccharide-based nanohydrogel cross-linked via electrostatic interactions between polyions. Due to the polycation-polyanion interactions nanohydrogel particles were formed instantly and spontaneously in water. The nanoparticles were colloidally stable and their size and surface charge could be controlled by the polycation/polyanion ratio. The morphology of the obtained particles was visualized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and atomic force microscopy (AFM). The resulting structures were spherical, with hydrodynamic diameters in the range of 100–150 nm. The binding constant (Ka) of a model drug, piroxicam, to the cationic pullulan (C-PUL) was determined by spectrophotometric measurements. The value of Ka was calculated according to the Benesi—Hildebrand equation to be (3.6 ± 0.2) × 103 M−1. After binding to cationic pullulan, piroxicam was effectively entrapped inside the nanohydrogel particles and released in a controlled way. The obtained system was efficiently taken up by cells and was shown to be biocompatible. Full article
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Review

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Open AccessReview
Recent Advances in Manufacturing Innovative Stents
Pharmaceutics 2020, 12(4), 349; https://doi.org/10.3390/pharmaceutics12040349 - 13 Apr 2020
Abstract
Cardiovascular diseases are the most distributed cause of death worldwide. Stenting of arteries as a percutaneous transluminal angioplasty procedure became a promising minimally invasive therapy based on re-opening narrowed arteries by stent insertion. In order to improve and optimize this method, many research [...] Read more.
Cardiovascular diseases are the most distributed cause of death worldwide. Stenting of arteries as a percutaneous transluminal angioplasty procedure became a promising minimally invasive therapy based on re-opening narrowed arteries by stent insertion. In order to improve and optimize this method, many research groups are focusing on designing new or improving existent stents. Since the beginning of the stent development in 1986, starting with bare-metal stents (BMS), these devices have been continuously enhanced by applying new materials, developing stent coatings based on inorganic and organic compounds including drugs, nanoparticles or biological components such as genes and cells, as well as adapting stent designs with different fabrication technologies. Drug eluting stents (DES) have been developed to overcome the main shortcomings of BMS or coated stents. Coatings are mainly applied to control biocompatibility, degradation rate, protein adsorption, and allow adequate endothelialization in order to ensure better clinical outcome of BMS, reducing restenosis and thrombosis. As coating materials (i) organic polymers: polyurethanes, poly(ε-caprolactone), styrene-b-isobutylene-b-styrene, polyhydroxybutyrates, poly(lactide-co-glycolide), and phosphoryl choline; (ii) biological components: vascular endothelial growth factor (VEGF) and anti-CD34 antibody and (iii) inorganic coatings: noble metals, wide class of oxides, nitrides, silicide and carbide, hydroxyapatite, diamond-like carbon, and others are used. DES were developed to reduce the tissue hyperplasia and in-stent restenosis utilizing antiproliferative substances like paclitaxel, limus (siro-, zotaro-, evero-, bio-, amphi-, tacro-limus), ABT-578, tyrphostin AGL-2043, genes, etc. The innovative solutions aim at overcoming the main limitations of the stent technology, such as in-stent restenosis and stent thrombosis, while maintaining the prime requirements on biocompatibility, biodegradability, and mechanical behavior. This paper provides an overview of the existing stent types, their functionality, materials, and manufacturing conditions demonstrating the still huge potential for the development of promising stent solutions. Full article
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Open AccessReview
Polymeric Nanocarriers of Drug Delivery Systems in Cancer Therapy
Pharmaceutics 2020, 12(4), 298; https://doi.org/10.3390/pharmaceutics12040298 - 25 Mar 2020
Cited by 1
Abstract
Conventional chemotherapy is the most common therapeutic method for treating cancer by the application of small toxic molecules thatinteract with DNA and causecell death. Unfortunately, these chemotherapeutic agents are non-selective and can damage both cancer and healthy tissues, producing diverse side effects, andthey [...] Read more.
Conventional chemotherapy is the most common therapeutic method for treating cancer by the application of small toxic molecules thatinteract with DNA and causecell death. Unfortunately, these chemotherapeutic agents are non-selective and can damage both cancer and healthy tissues, producing diverse side effects, andthey can have a short circulation half-life and limited targeting. Many synthetic polymers have found application as nanocarriers of intelligent drug delivery systems (DDSs). Their unique physicochemical properties allow them to carry drugs with high efficiency, specificallytarget cancer tissue and control drug release. In recent years, considerable efforts have been made to design smart nanoplatforms, including amphiphilic block copolymers, polymer-drug conjugates and in particular pH- and redox-stimuli-responsive nanoparticles (NPs). This review is focused on a new generation of polymer-based DDSs with specific chemical functionalities that improve their hydrophilicity, drug loading and cellular interactions.Recentlydesigned multifunctional DDSs used in cancer therapy are highlighted in this review. Full article
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Open AccessReview
Nanoconjugation and Encapsulation Strategies for Improving Drug Delivery and Therapeutic Efficacy of Poorly Water-Soluble Drugs
Pharmaceutics 2019, 11(7), 325; https://doi.org/10.3390/pharmaceutics11070325 - 10 Jul 2019
Cited by 11
Abstract
Nanoconjugations have been demonstrated to be a dominant strategy for drug delivery and biomedical applications. In this review, we intend to describe several strategies for drug formulation, especially to improve the bioavailability of poorly water-soluble molecules for future application in the therapy of [...] Read more.
Nanoconjugations have been demonstrated to be a dominant strategy for drug delivery and biomedical applications. In this review, we intend to describe several strategies for drug formulation, especially to improve the bioavailability of poorly water-soluble molecules for future application in the therapy of numerous diseases. The context of current studies will give readers an overview of the conjugation strategies for fabricating nanoparticles, which have expanded from conjugated materials to the surface conjugation of nanovehicles. Moreover, nanoconjugates for theranostics are also discussed and highlighted. Overall, these state-of-the-art conjugation methods and these techniques and applications for nanoparticulate systems of poorly water-soluble drugs will inspire scientists to explore and discover more productive techniques and methodologies for drug development. Full article
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