Polysaccharides in Ocular Drug Delivery

Polysaccharides, such as cellulose, hyaluronic acid, alginic acid, and chitosan, as well as polysaccharide derivatives, have been successfully used to augment drug delivery in the treatment of ocular pathologies. The properties of polysaccharides can be extensively modified to optimize ocular drug formulations and to obtain biocompatible and biodegradable drugs with improved bioavailability and tailored pharmacological effects. This review discusses the available polysaccharide choices for overcoming the difficulties associated with ocular drug delivery, and it explores the reasons for the dependence between the physicochemical properties of polysaccharide-based drug carriers and their efficiency in different formulations and applications. Polysaccharides will continue to be of great interest to researchers endeavoring to develop ophthalmic drugs with improved effectiveness and safety.Peer reviewe

Effect of Double Substitution in Cationic Chitosan Derivatives on DNA Transfection Efficiency

Recently, much effort has been expended on the development of non-viral gene delivery systems based on polyplexes of nucleic acids with various cationic polymers. Natural polysaccharide derivatives are promising carriers due to their low toxicity. In this work, chitosan was chemically modified by a reaction with 4-formyl-n,n,n-trimethylanilinium iodide and pyridoxal hydrochloride and subsequent reduction of the imine bond with NaBH4. This reaction yielded three novel derivatives, n-[4-(n',n',n'-trimethylammonium)benzyl]chitosan chloride (TMAB-CS), n-[(3-hydroxy-5-(hydroxymethyl)-2-methyl-4-pyridine)methyl]chitosan chloride (Pyr-CS), and n-[4-(n',n',n''-trimethylammonium)benzyl]-n-[(3-hydroxy-5-(hydroxymethyl)-2-methyl-4-pyridine)methyl]chitosan chloride (PyrTMAB-CS). Their structures and degrees of substitution were established by H-1 NMR spectroscopy as DS1 = 0.22 for TMAB-CS, DS2 = 0.28 for Pyr-CS, and DS1 = 0.21, DS2 = 0.22 for PyrTMAB-CS. Dynamic light scattering measurements revealed that the new polymers formed stable polyplexes with plasmid DNA encoding the green fluorescent protein (pEGFP-N3) and that the particles had the smallest size (110-165 nm) when the polymer:DNA mass ratio was higher than 5:1. Transfection experiments carried out in the HEK293 cell line using the polymer:DNA polyplexes demonstrated that Pyr-CS was a rather poor transfection agent at polymer:DNA mass ratios less than 10:1, but it was still more effective than the TMAB-CS and PyrTMAB-CS derivatives that contained a quaternary ammonium group. By contrast, TMAB-CS and PyrTMAB-CS were substantially more effective than Pyr-CS at higher polymer:DNA mass ratios and showed a maximum efficiency at 200:1 (50%-70% transfected cells). Overall, the results show the possibility of combining substituent effects in a single carrier, thereby increasing its efficacy.Peer reviewe

Biopolymers in Drug and Gene Delivery Systems

Recent years have seen remarkable advances in the field of drug and gene delivery systems, revolutionizing the way we approach therapeutic treatments [...

Patches as Polymeric Systems for Improved Delivery of Topical Corticosteroids: Advances and Future Perspectives

Mucoadhesive polymer patches are a promising alternative for prolonged and controlled delivery of topical corticosteroids (CS) to improve their biopharmaceutical properties (mainly increasing local bioavailability and reducing systemic toxicity). The main biopharmaceutical advantages of patches compared to traditional oral dosage forms are their excellent bioadhesive properties and their increased drug residence time, modified and unidirectional drug release, improved local bioavailability and safety profile, additional pain receptor protection, and patient friendliness. This review describes the main approaches that can be used for the pharmaceutical R&D of oromucosal patches with improved physicochemical, mechanical, and pharmacological properties. The review mainly focuses on ways to increase the bioadhesion of oromucosal patches and to modify drug release, as well as ways to improve local bioavailability and safety by developing unidirectional -release poly-layer patches. Various techniques for obtaining patches and their influence on the structure and properties of the resulting dosage forms are also presented

Polymyxin Delivery Systems: Recent Advances and Challenges

Polymyxins are vital antibiotics for the treatment of multiresistant Gram-negative ESKAPE pathogen infections. However, their clinical value is limited by their high nephrotoxicity and neurotoxicity, as well as their poor permeability and absorption in the gastrointestinal tract. This review focuses on various polymyxin delivery systems that improve polymyxin bioavailability and reduce drug toxicity through targeted and controlled release. Currently, the most suitable systems for improving oral, inhalation, and parenteral polymyxin delivery are polymer particles, liposomes, and conjugates, while gels, polymer fibers, and membranes are attractive materials for topical administration of polymyxin for the treatment of infected wounds and burns. In general, the application of these systems protects polymyxin molecules from the negative effects of both physiological and pathological factors while achieving higher concentrations at the target site and reducing dosage and toxicity. Improving the properties of polymyxin will be of great interest to researchers who are focused on developing antimicrobial drugs that show increased efficacy and safety

Nano-Sized Fucoidan Interpolyelectrolyte Complexes: Recent Advances in Design and Prospects for Biomedical Applications

The marine polysaccharide fucoidan (FUC) is a promising polymer for pharmaceutical research and development of novel drug delivery systems with modified release and targeted delivery. The presence of a sulfate group in the polysaccharide makes FUC an excellent candidate for the formation of interpolyelectrolyte complexes (PECs) with various polycations. However, due to the structural diversity of FUC, the design of FUC-based nanoformulations is challenging. This review describes the main strategies for the use of FUC-based PECs to develop drug delivery systems with improved biopharmaceutical properties, including nanocarriers in the form of FUC–chitosan PECs for pH-sensitive oral delivery, targeted delivery systems, and polymeric nanoparticles for improved hydrophobic drug delivery (e.g., FUC-zein PECs, core-shell structures obtained by the layer-by-layer self-assembly method, and self-assembled hydrophobically modified FUC particles). The importance of a complex study of the FUC structure, and the formation process of PECs based on it for obtaining reproducible polymeric nanoformulations with the desired properties, is also discussed

Cellulose Cryogels as Promising Materials for Biomedical Applications

The availability, biocompatibility, non-toxicity, and ease of chemical modification make cellulose a promising natural polymer for the production of biomedical materials. Cryogelation is a relatively new and straightforward technique for producing porous light and super-macroporous cellulose materials. The production stages include dissolution of cellulose in an appropriate solvent, regeneration (coagulation) from the solution, removal of the excessive solvent, and then freezing. Subsequent freeze-drying preserves the micro- and nanostructures of the material formed during the regeneration and freezing steps. Various factors can affect the structure and properties of cellulose cryogels, including the cellulose origin, the dissolution parameters, the solvent type, and the temperature and rate of freezing, as well as the inclusion of different fillers. Adjustment of these parameters can change the morphology and properties of cellulose cryogels to impart the desired characteristics. This review discusses the structure of cellulose and its properties as a biomaterial, the strategies for cellulose dissolution, and the factors affecting the structure and properties of the formed cryogels. We focus on the advantages of the freeze-drying process, highlighting recent studies on the production and application of cellulose cryogels in biomedicine and the main cryogel quality characteristics. Finally, conclusions and prospects are presented regarding the application of cellulose cryogels in wound healing, in the regeneration of various tissues (e.g., damaged cartilage, bone tissue, and nerves), and in controlled-release drug delivery

Dexamethasone Conjugates: Synthetic Approaches and Medical Prospects

Dexamethasone (DEX) is the most commonly prescribed glucocorticoid (GC) and has a wide spectrum of pharmacological activity. However, steroid drugs like DEX can have severe side effects on non-target organs. One strategy to reduce these side effects is to develop targeted systems with the controlled release by conjugation to polymeric carriers. This review describes the methods available for the synthesis of DEX conjugates (carbodiimide chemistry, solid-phase synthesis, reversible addition fragmentation-chain transfer [RAFT] polymerization, click reactions, and 2-iminothiolane chemistry) and perspectives for their medical application as GC drug or gene delivery systems for anti-tumor therapy. Additionally, the review focuses on the development of DEX conjugates with different physical-chemical properties as successful delivery systems in the target organs such as eye, joint, kidney, and others. Finally, polymer conjugates with improved transfection activity in which DEX is used as a vector for gene delivery in the cell nucleus have been described

Sodium Alginate–Gelatin Nanoformulations for Encapsulation of Bacillus velezensis and Their Use for Biological Control of Pistachio Gummosis

Biopolymer-based nanocomposites are favorable materials for the encapsulation of biofertilizers and biocontrol agents. In this research, sodium alginate, a widely used natural polymer, was extracted and purified from Macrocystis pyrifera. Its composition was confirmed using 1H NMR and FTIR analyses, and its molecular weight and mannuronic acid/guluronic acid ratio were obtained. Sodium alginate–gelatin microcapsules enriched with carbon nanotubes and SiO2 nanoparticles were prepared to encapsulate Bacillus velezensis, and the biological effects of this formulation on the control of pistachio gummosis and growth parameters were investigated. Microscopy examination showed that the microcapsules had quite globular shapes. XRD confirmed the occurrence of an electrostatic interaction when sodium alginate was blended with gelatin. The survival rate of the encapsulated bacteria was about 107 CFU/mL and was maintained after one year of storage. The aim of this study was to achieve a unique formulation containing beneficial bacteria and nanoparticles for the synergistic control of Phytophthora drechsleri

pH-Sensitive Drug Delivery System Based on Chitin Nanowhiskers–Sodium Alginate Polyelectrolyte Complex

Polyelectrolyte complexes (PECs), based on partially deacetylated chitin nanowhiskers (CNWs) and anionic polysaccharides, are characterized by their variability of properties (particle size, ζ-potential, and pH-sensitivity) depending on the preparation conditions, thereby allowing the development of polymeric nanoplatforms with a sustained release profile for active pharmaceutical substances. This study is focused on the development of hydrogels based on PECs of CNWs and sodium alginate (ALG) for potential vaginal administration that provide controlled pH-dependent antibiotic release in an acidic vaginal environment, as well as prolonged pharmacological action due to both the sustained drug release profile and the mucoadhesive properties of the polysaccharides. The desired hydrogels were formed as a result of both electrostatic interactions between CNWs and ALG (PEC formation), and the subsequent molecular entanglement of ALG chains, and the formation of additional hydrogen bonds. Metronidazole (MET) delivery systems with the desired properties were obtained at pH 5.5 and an CNW:ALG ratio of 1:2. The MET–CNW–ALG microparticles in the hydrogel composition had an apparent hydrodynamic diameter of approximately 1.7 µm and a ζ-potential of −43 mV. In vitro release studies showed a prolonged pH-sensitive drug release from the designed hydrogels; 37 and 67% of MET were released within 24 h at pH 7.4 and pH 4.5, respectively. The introduction of CNWs into the MET–ALG system not only prolonged the drug release, but also increased the mucoadhesive properties by about 1.3 times. Thus, novel CNW–ALG hydrogels are promising carriers for pH sensitive drug delivery carriers