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Pharmaceuticals
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Chitosan Based Novel Pharmaceutical Dosage Forms and Drug Delivery Systems
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Chitosan Based Novel Pharmaceutical Dosage Forms and Drug Delivery Systems

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmaceutical Technology".

Deadline for manuscript submissions: 24 January 2025 | Viewed by 19636

Special Issue Editors

Prof. Dr. Ljiljana Djekic

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Guest Editor
Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, 11221 Belgrade, Serbia
Interests: pharmaceutical dosage form design; polymer-based drug delivery systems; lipid-based drug delivery systems; microencapsulation; nanoencapsulation; controlled drug delivery
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Anđelija M. Malenović

E-Mail Website
Co-Guest Editor
Department of Drug Analysis, Faculty of Pharmacy, University of Belgrade, Belgrade 11221, Serbia
Interests: pharmaceutical analysis; analytical method development and validation; bioanalytical method development and validation; mass spectrometry; chemometrics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

During the past decade, chitosan, a linear mucopolysaccharide obtained by N-deacetylation of chitin, has gained significant attention in the drug delivery arena due to its exceptional physicochemical characteristics (broad range of average molecular weight, presence of hydroxyl and amino groups), biological properties (biocompatibility, non-immunogenicity, biodegradability, mucoadhesive character, absorption enhancing capability, inhibition of efflux pumps, etc.), and natural abundance. The inherent limitations of pure chitosan, such as low water solubility at pH>6.5, poor drug entrapment capacity, and limited ability to control drug release, rise attention toward formulations and carriers designed from chemically modified (grafted) chitosan, chitosan–sugar hybrids, and chitosan/polyanions polyelectrolyte complexes, as well as for different composite systems obtained by combining chitosan with other drug carriers so as to enhance overall drug delivery performances. In this way, a versatile strategy is created that can be applied in the development of conventional dosage forms (tablets, capsules, hydrogels, membranes, films, sponges, fibers, beads), microscale and nanoscale carriers (microbeads, microneedles, micro-/nanoparticles, micelles, nanofibers, nanogels), which can efficiently entrap a variety of hydrophilic and lipophilic small molecule drugs, peptides, proteins, or genes, allowing various administration routes and drug release mechanisms. In recent years, a research interest focuses on smart chitosan-based carriers able for more accurate control of drug distribution in target tissues and/or drug release under specified conditions (pH, enzyme, temperature, light, ultrasound, magnetism, pressure, electric fields), which are favorable for optimization of therapeutical efficacy and reduction of side effects. At the same time, several challenges need to be overcome on the way to clinical validation of these strategies. This Special Issue aims to collect reviews that consider the current state of the art and future prospects in the field of chitosan-based formulations and drug delivery systems, as well as original research articles reflecting recent research efforts in this area.

Prof. Dr. Ljiljana Djekic
Guest Editor
Prof. Dr. Anđelija M. Malenović
Co-Guest Editor

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Keywords

  • chitosan
  • chitosan derivatives
  • chitosan grafted copolymers
  • chitosan-ligand conjugates
  • chitosan/polyanions polyelectrolyte complexes
  • formulation development
  • drug delivery systems
  • controlled drug release
  • drug targeting

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Published Papers (6 papers)

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Research

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25 pages, 4471 KiB  
Article
Matrix Tablets Based on Chitosan–Carrageenan Polyelectrolyte Complex: Unique Matrices for Drug Targeting in the Intestine
by Alena Komersová, Roman Svoboda, Barbora Skalická, Martin Bartoš, Eva Šnejdrová, Jitka Mužíková and Kevin Matzick
Pharmaceuticals 2022, 15(8), 980; https://doi.org/10.3390/ph15080980 - 9 Aug 2022
Cited by 4 | Viewed by 2166
Abstract
The present study focused on the more detailed characterization of chitosan–carrageenan-based matrix tablets with respect to their potential utilization for drug targeting in the intestine. The study systematically dealt with the particular stages of the dissolution process, as well as with different views [...] Read more.
The present study focused on the more detailed characterization of chitosan–carrageenan-based matrix tablets with respect to their potential utilization for drug targeting in the intestine. The study systematically dealt with the particular stages of the dissolution process, as well as with different views of the physico-chemical processes involved in these stages. The initial swelling of the tablets in the acidic medium based on the combined microscopy–calorimetry point of view, the pH-induced differences in the erosion and swelling of the tested tablets, and the morphological characterization of the tablets are discussed. The dissolution kinetics correlated with the rheological properties and mucoadhesive behavior of the tablets are also reported, and, correspondingly, the formulations with suitable properties were identified. It was confirmed that the formation of the chitosan–carrageenan polyelectrolyte complex may be an elegant and beneficial alternative solution for the drug targeting to the intestine by the matrix tablet. Full article
(This article belongs to the Special Issue Chitosan Based Novel Pharmaceutical Dosage Forms and Drug Delivery Systems)
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19 pages, 3199 KiB  
Article
Improvement of Biocatalytic Properties and Cytotoxic Activity of L-Asparaginase from Rhodospirillum rubrum by Conjugation with Chitosan-Based Cationic Polyelectrolytes
by Natalia V. Dobryakova, Dmitry D. Zhdanov, Nikolay N. Sokolov, Svetlana S. Aleksandrova, Marina V. Pokrovskaya and Elena V. Kudryashova
Pharmaceuticals 2022, 15(4), 406; https://doi.org/10.3390/ph15040406 - 27 Mar 2022
Cited by 10 | Viewed by 2327
Abstract
L-asparaginases (L-ASNases, EC 3.5.1.1) are a family of enzymes that are widely used for the treatment of lymphoblastic leukemias. L-ASNase from Rhodospirillum rubrum (RrA) has a low molecular weight, low glutaminase activity, and low immunogenicity, making it a promising enzyme for antitumor drug [...] Read more.
L-asparaginases (L-ASNases, EC 3.5.1.1) are a family of enzymes that are widely used for the treatment of lymphoblastic leukemias. L-ASNase from Rhodospirillum rubrum (RrA) has a low molecular weight, low glutaminase activity, and low immunogenicity, making it a promising enzyme for antitumor drug development. In our work, the complex formation and covalent conjugation of the enzyme with synthetic or natural polycationic polymers was studied. Among non-covalent polyelectrolyte complexes (PEC), polyethyleneimine (PEI) yielded the highest effect on RrA, increasing its activity by 30%. The RrA-PEI complex had increased stability to trypsinolysis, with an inactivation constant decrease up to 10-fold compared to that of the native enzyme. The covalent conjugation of RrA with chitosan-PEI, chitosan-polyethylene glycol (chitosan-PEG), and chitosan-glycol resulted in an increase in the specific activity of L-asparagine (up to 30%). RrA-chitosan-PEG demonstrated dramatically (by 60%) increased cytotoxic activity for human chronic myeloma leukemia K562 cells in comparison to the native enzyme. The antiproliferative activity of RrA and its conjugates was significantly higher (up to 50%) than for that of the commercially available EcA at the same concentration. The results of this study demonstrated that RrA conjugates with polycations can become a promising strategy for antitumor drug development. Full article
(This article belongs to the Special Issue Chitosan Based Novel Pharmaceutical Dosage Forms and Drug Delivery Systems)
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18 pages, 4405 KiB  
Article
Formulation of Chitosan-Coated Brigatinib Nanospanlastics: Optimization, Characterization, Stability Assessment and In-Vitro Cytotoxicity Activity against H-1975 Cell Lines
by Randa Mohammed Zaki, Munerah M. Alfadhel, Saad M. Alshahrani, Ahmed Alsaqr, Layla A. Al-Kharashi and Md Khalid Anwer
Pharmaceuticals 2022, 15(3), 348; https://doi.org/10.3390/ph15030348 - 13 Mar 2022
Cited by 14 | Viewed by 2571
Abstract
The purpose of the current study was to develop Brigatinib (BGT)-loaded nanospanlastics (BGT-loaded NSPs) (S1-S13) containing Span 60 with different edge activators (Tween 80 and Pluronic F127) and optimized based on the vesicle size, zeta potential (ZP), and percent entrapment efficiency (%EE) using [...] Read more.
The purpose of the current study was to develop Brigatinib (BGT)-loaded nanospanlastics (BGT-loaded NSPs) (S1-S13) containing Span 60 with different edge activators (Tween 80 and Pluronic F127) and optimized based on the vesicle size, zeta potential (ZP), and percent entrapment efficiency (%EE) using Design-Expert® software. The optimum formula was recommended with desirability of 0.819 and composed of Span-60:Tween 80 at a ratio of 4:1 and 10 min as a sonication time (S13). It showed predicted EE% (81.58%), vesicle size (386.55 nm), and ZP (−29.51 mv). The optimized nanospanlastics (S13) was further coated with chitosan and further evaluated for Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), in vitro release, Transmission Electron Microscopy (TEM), stability and in-vitro cytotoxicity studies against H-1975 lung cancer cell lines. The DSC and XRD revealed complete encapsulation of the drug. TEM imagery revealed spherical nanovesicles with a smooth surface. Also, the coated formula showed high stability for three months in two different conditions. Moreover, it resulted in improved and sustained drug release than free BGT suspension and exhibited Higuchi kinetic release mechanism. The cytotoxic activity of BGT-loaded SPs (S13) was enhanced three times in comparison to free the BGT drug against the H-1975 cell lines. Overall, these results confirmed that BGT-loaded SPs could be a promising nanocarrier to improve the anticancer efficacy of BGT. Full article
(This article belongs to the Special Issue Chitosan Based Novel Pharmaceutical Dosage Forms and Drug Delivery Systems)
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18 pages, 32150 KiB  
Article
Lipid Nanocarriers Overlaid with Chitosan for Brain Delivery of Berberine via the Nasal Route
by Hadel A. Abo El-Enin, Mohammed H. Elkomy, Ibrahim A. Naguib, Marwa F. Ahmed, Omar A. Alsaidan, Izzeddin Alsalahat, Mohammed M. Ghoneim and Hussein M. Eid
Pharmaceuticals 2022, 15(3), 281; https://doi.org/10.3390/ph15030281 - 24 Feb 2022
Cited by 38 | Viewed by 3752
Abstract
This research aimed to design, optimize, and evaluate berberine-laden nanostructured lipid carriers overlaid with chitosan (BER-CTS-NLCs) for efficient brain delivery via the intranasal route. The nanostructured lipid carriers containing berberine (BER-NLCs) were formulated via hot homogenization and ultrasonication strategy and optimized for the [...] Read more.
This research aimed to design, optimize, and evaluate berberine-laden nanostructured lipid carriers overlaid with chitosan (BER-CTS-NLCs) for efficient brain delivery via the intranasal route. The nanostructured lipid carriers containing berberine (BER-NLCs) were formulated via hot homogenization and ultrasonication strategy and optimized for the influence of a variety of causal variables, including the amount of glycerol monostearate (solid lipid), poloxamer 407 (surfactant) concentration, and oleic acid (liquid lipid) amount, on size of the particles, entrapment, and the total drug release after 24 h. The optimal BER-NLCs formulation was then coated with chitosan. Their diameter, in vitro release, surface charge, morphology, ex vivo permeability, pH, histological, and in vivo (pharmacokinetics and brain uptake) parameters were estimated. BER-CTS-NLCs had a size of 180.9 ± 4.3 nm, sustained-release properties, positive surface charge of 36.8 mV, and augmented ex-vivo permeation via nasal mucosa. The histopathological assessment revealed that the BER-CTS-NLCs system is safe for nasal delivery. Pharmacokinetic and brain accumulation experiments showed that animals treated intranasally with BER-CTS-NLCs had substantially greater drug levels in the brain. The ratios of BER brain/blood levels at 30 min, AUCbrain/AUCblood, drug transport percentage, and drug targeting efficiency for BER-CTS-NLCs (IN) were higher compared to BER solution (IN), suggesting enhanced brain targeting. The optimized nanoparticulate system is speculated to be a successful approach for boosting the effect of BER in treating CNS diseases, such as Alzheimer’s disease, through intranasal therapy. Full article
(This article belongs to the Special Issue Chitosan Based Novel Pharmaceutical Dosage Forms and Drug Delivery Systems)
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17 pages, 19814 KiB  
Article
Chitosan/Sodium Dodecyl Sulfate Complexes for Microencapsulation of Vitamin E and Its Release Profile—Understanding the Effect of Anionic Surfactant
by Jelena Milinković Budinčić, Lidija Petrović, Ljiljana Đekić, Milijana Aleksić, Jadranka Fraj, Senka Popović, Sandra Bučko, Jaroslav Katona, Ljiljana Spasojević, Jelena Škrbić and Anđelija Malenović
Pharmaceuticals 2022, 15(1), 54; https://doi.org/10.3390/ph15010054 - 31 Dec 2021
Cited by 12 | Viewed by 2674
Abstract
Microencapsulation of bioactive substances is a common strategy for their protection and release rate control. The use of chitosan (Ch) is particularly promising due to its abundance, biocompatibility, and interaction with anionic surfactants to form complexes of different characteristics with relevance for use [...] Read more.
Microencapsulation of bioactive substances is a common strategy for their protection and release rate control. The use of chitosan (Ch) is particularly promising due to its abundance, biocompatibility, and interaction with anionic surfactants to form complexes of different characteristics with relevance for use in microcapsule wall design. In this study, Ch/sodium dodecyl sulfate (SDS) microcapsules, without and with cross-linking agent (formaldehyde (FA) or glutaraldehyde (GA)), were obtained by the spray drying of vitamin E loaded oil-in-water emulsion. All of the microcapsules had good stability during the drying process. Depending on the composition, their product yield, moisture content, and encapsulation efficiency varied between 11–34%, 1.14–1.62%, and 94–126%, respectively. SEM and FTIR analysis results indicate that SDS as well as cross-linkers significantly affected the microcapsule wall properties. The profiles of in vitro vitamin E release from the investigated microcapsules fit with the Korsmeyer-Peppas model (r2 > 0.9). The chemical structure of the anionic surfactant was found to have a significant effect on the vitamin E release mechanism. Ch/SDS coacervates may build a microcapsule wall without toxic crosslinkers. This enabled the combined diffusion/swelling based release mechanism of the encapsulated lipophilic substance, which can be considered favorable for utilization in food and pharmaceutical products. Full article
(This article belongs to the Special Issue Chitosan Based Novel Pharmaceutical Dosage Forms and Drug Delivery Systems)
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Review

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25 pages, 11701 KiB  
Review
Chitosan Based MicroRNA Nanocarriers
by Hussein H. Genedy, Thierry Delair and Alexandra Montembault
Pharmaceuticals 2022, 15(9), 1036; https://doi.org/10.3390/ph15091036 - 23 Aug 2022
Cited by 15 | Viewed by 3277
Abstract
Vectorization of microRNAs has shown to be a smart approach for their potential delivery to treat many diseases (i.e., cancer, osteopathy, vascular, and infectious diseases). However, there are barriers to genetic in vivo delivery regarding stability, targeting, specificity, and internalization. Polymeric nanoparticles can [...] Read more.
Vectorization of microRNAs has shown to be a smart approach for their potential delivery to treat many diseases (i.e., cancer, osteopathy, vascular, and infectious diseases). However, there are barriers to genetic in vivo delivery regarding stability, targeting, specificity, and internalization. Polymeric nanoparticles can be very promising candidates to overcome these challenges. One of the most suitable polymers for this purpose is chitosan. Chitosan (CS), a biodegradable biocompatible natural polysaccharide, has always been of interest for drug and gene delivery. Being cationic, chitosan can easily form particles with anionic polymers to encapsulate microRNA or even complex readily forming polyplexes. However, fine tuning of chitosan characteristics is necessary for a successful formulation. In this review, we cover all chitosan miRNA formulations investigated in the last 10 years, to the best of our knowledge, so that we can distinguish their differences in terms of materials, formulation processes, and intended applications. The factors that make some optimized systems superior to their predecessors are also discussed to reach the highest potential of chitosan microRNA nanocarriers. Full article
(This article belongs to the Special Issue Chitosan Based Novel Pharmaceutical Dosage Forms and Drug Delivery Systems)
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