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1.
Int J Mol Sci ; 25(10)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38791397

RESUMO

Oromucosal drug delivery, both local and transmucosal (buccal), is an effective alternative to traditional oral and parenteral dosage forms because it increases drug bioavailability and reduces systemic drug toxicity. The oral mucosa has a good blood supply, which ensures that drug molecules enter the systemic circulation directly, avoiding drug metabolism during the first passage through the liver. At the same time, the mucosa has a number of barriers, including mucus, epithelium, enzymes, and immunocompetent cells, that are designed to prevent the entry of foreign substances into the body, which also complicates the absorption of drugs. The development of oromucosal drug delivery systems based on mucoadhesive biopolymers and their derivatives (especially thiolated and catecholated derivatives) is a promising strategy for the pharmaceutical development of safe and effective dosage forms. Solid, semi-solid and liquid pharmaceutical formulations based on biopolymers have several advantageous properties, such as prolonged residence time on the mucosa due to high mucoadhesion, unidirectional and modified drug release capabilities, and enhanced drug permeability. Biopolymers are non-toxic, biocompatible, biodegradable and may possess intrinsic bioactivity. A rational approach to the design of oromucosal delivery systems requires an understanding of both the anatomy/physiology of the oral mucosa and the physicochemical and biopharmaceutical properties of the drug molecule/biopolymer, as presented in this review. This review summarizes the advances in the pharmaceutical development of mucoadhesive oromucosal dosage forms (e.g., patches, buccal tablets, and hydrogel systems), including nanotechnology-based biopolymer nanoparticle delivery systems (e.g., solid lipid particles, liposomes, biopolymer polyelectrolyte particles, hybrid nanoparticles, etc.).


Assuntos
Sistemas de Liberação de Medicamentos , Mucosa Bucal , Humanos , Biopolímeros/química , Sistemas de Liberação de Medicamentos/métodos , Mucosa Bucal/metabolismo , Animais
2.
Int J Mol Sci ; 24(16)2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37628943

RESUMO

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


Assuntos
Técnicas de Transferência de Genes , Preparações Farmacêuticas , Biopolímeros
3.
Int J Mol Sci ; 24(23)2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38069419

RESUMO

In recent years, significant progress has been made in the design and development of biopolymer-based delivery systems for a wide range of applications, including cancer therapy, gene editing, regenerative medicine, and vaccine delivery [...].


Assuntos
Sistemas de Liberação de Medicamentos , Medicina Regenerativa , Preparações Farmacêuticas , Biopolímeros
4.
Int J Mol Sci ; 24(3)2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36768936

RESUMO

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.


Assuntos
Quitosana , Polissacarídeos , Polissacarídeos/química , Sistemas de Liberação de Medicamentos , Quitosana/química , Interações Hidrofóbicas e Hidrofílicas
5.
Int J Mol Sci ; 24(14)2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37511308

RESUMO

Polymeric drug delivery systems enhance the biopharmaceutical properties of antibiotics by increasing their bioavailability, providing programmable and controlled-release properties, and reducing toxicity. In addition, drug delivery systems are a promising strategy to improve the intestinal permeability of various antimicrobial agents, including colistin (CT). This study describes the modification of conjugates based on CT and hyaluronic acid (HA) with cyanocobalamin (vitamin B12). Vitamin B12 was chosen as a targeting ligand because it has its own absorption pathway in the small intestine. The resulting polysaccharide conjugates contained 95 µg/mg vitamin B12 and the CT content was 335 µg/mg; they consisted of particles of two sizes, 98 and 702 nm, with a ζ-potential of approximately -25 mV. An in vitro release test at pH 7.4 and pH 5.2 showed an ultra-slow release of colistin of approximately 1% after 10 h. The modified B12 conjugates retained their antimicrobial activity at the level of pure CT (minimum inhibitory concentration was 2 µg/mL). The resulting delivery systems also reduced the nephrotoxicity of CT by 30-40% (HEK 293 cell line). In addition, the modification of B12 improved the intestinal permeability of CT, and the apparent permeability coefficient of HA-CT-B12 conjugates was 3.5 × 10-6 cm/s, corresponding to an in vivo intestinal absorption of 50-100%. Thus, vitamin-B12-modified conjugates based on CT and HA may be promising oral delivery systems with improved biopharmaceutical properties.


Assuntos
Colistina , Ácido Hialurônico , Humanos , Colistina/farmacologia , Ácido Hialurônico/química , Células HEK293 , Vitamina B 12 , Sistemas de Liberação de Medicamentos/métodos
6.
Int J Mol Sci ; 24(6)2023 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-36982493

RESUMO

In this work, new composite films were prepared by incorporating the disintegrated bacterial cellulose (BCd) nanofibers and cerium oxide nanoparticles into chitosan (CS) matrices. The influence of the amount of nanofillers on the structure and properties of the polymer composites and the specific features of the intermolecular interactions in the materials were determined. An increase in film stiffness was observed as a result of reinforcing the CS matrix with BCd nanofibers: the Young's modulus increased from 4.55 to 6.3 GPa with the introduction of 5% BCd. A further increase in Young's modulus of 6.7 GPa and a significant increase in film strength (22% increase in yield stress compared to the CS film) were observed when the BCd concentration was increased to 20%. The amount of nanosized ceria affected the structure of the composite, followed by a change in the hydrophilic properties and texture of the composite films. Increasing the amount of nanoceria to 8% significantly improved the biocompatibility of the films and their adhesion to the culture of mesenchymal stem cells. The obtained nanocomposite films combine a number of favorable properties (good mechanical strength in dry and swollen states, improved biocompatibility in relation to the culture of mesenchymal stem cells), which allows us to recommend them for use as a matrix material for the culture of mesenchymal stem cells and wound dressings.


Assuntos
Quitosana , Nanocompostos , Nanofibras , Quitosana/química , Celulose/química , Nanofibras/química , Resistência à Tração , Nanocompostos/química
7.
Int J Mol Sci ; 23(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36361769

RESUMO

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.


Assuntos
Produtos Biológicos , Sistemas de Liberação de Medicamentos , Humanos , Sistemas de Liberação de Medicamentos/métodos , Polímeros/química , Preparações Farmacêuticas , Corticosteroides
8.
Int J Mol Sci ; 23(4)2022 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-35216150

RESUMO

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.


Assuntos
Celulose/análogos & derivados , Criogéis/química , Nanomedicina/métodos , Engenharia Tecidual/métodos , Animais , Liofilização/métodos , Humanos
9.
Int J Mol Sci ; 24(1)2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36613610

RESUMO

The growth of microbial multidrug resistance is a problem in modern clinical medicine. Chemical modification of active pharmaceutical ingredients is an attractive strategy to improve their biopharmaceutical properties by increasing bioavailability and reducing drug toxicity. Conjugation of antimicrobial drugs with natural polysaccharides provides high efficiency of these systems due to targeted delivery, controlled drug release and reduced toxicity. This paper reports a two-step synthesis of colistin conjugates (CT) with succinyl chitosan (SucCS); first, we modified chitosan with succinyl anhydride to introduce a carboxyl function into the polymer molecule, which was then used for chemical grafting with amino groups of the peptide antibiotic CT using carbodiimide chemistry. The resulting polymeric delivery systems had a degree of substitution (DS) by CT of 3-8%, with conjugation efficiencies ranging from 54 to 100% and CT contents ranging from 130-318 µg/mg. The size of the obtained particles was 100-200 nm, and the ζ-potential varied from -22 to -28 mV. In vitro release studies at pH 7.4 demonstrated ultra-slow hydrolysis of amide bonds, with a CT release of 0.1-0.5% after 12 h; at pH 5.2, the hydrolysis rate slightly increased; however, it remained extremely low (1.5% of CT was released after 12 h). The antimicrobial activity of the conjugates depended on the DS. At DS 8%, the minimum inhibitory concentration (MIC) of the conjugate was equal to the MIC of native CT (1 µg/mL); at DS of 3 and 5%, the MIC increased 8-fold. In addition, the developed systems reduced CT nephrotoxicity by 20-60%; they also demonstrated the ability to reduce bacterial lipopolysaccharide-induced inflammation in vitro. Thus, these promising CT-SucCS conjugates are prospective for developing safe and effective nanoantibiotics.


Assuntos
Quitosana , Colistina , Colistina/farmacologia , Quitosana/química , Estudos Prospectivos , Sistemas de Liberação de Medicamentos , Antibacterianos/farmacologia , Antibacterianos/química
10.
BMC Pulm Med ; 21(1): 418, 2021 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-34922518

RESUMO

BACKGROUND: Mechanisms of positive effects of pulmonary artery (PA) denervation (PADN) remain poorly understood. The study aimed to evaluate pulmonary hemodynamic changes after PADN and their association with the extent of PA wall damage in an acute thromboxane A2 (TXA2)-induced pulmonary hypertension (PH) model in swine. METHODS: In this experimental sham-controlled study, 17 normotensive male white Landrace pigs (the mean weight 36.2 ± 4.5 kg) were included and randomly assigned to group I (n = 9)-PH modeling before and after PADN, group II (n = 4)-PADN only, or group III (n = 4)-PH modeling before and after a sham procedure. Radiofrequency (RF) PADN was performed in the PA trunk and at the proximal parts of the right and left PAs. PA wall lesions were characterized at the autopsy study using histological and the immunohistochemical examination. RESULTS: In groups I and II, no statistically significant changes in the mean pulmonary arterial pressure nor systemic blood pressure were found after PADN (-0.8 ± 3.4 vs 4.3 ± 8.6 mmHg, P = 0.47; and 6.0 ± 15.9 vs -8.3 ± 7.5 mmHg, P = 0.1; correspondingly). There was a trend towards a lower diastolic pulmonary arterial pressure after PADN in group I when compared with group III during repeat PH induction (34.4 ± 2.9 vs 38.0 ± 0.8; P = 0.06). Despite the presence of severe PA wall damage at the RF application sites, S100 expression was preserved in the majority of PA specimens. The presence of high-grade PA lesions was associated with HR acceleration after PADN (ρ = 0.68, p = 0.03). No significant correlation was found between the grade of PA lesion severity and PA pressure after PADN with or without PH induction. CONCLUSIONS: Extended PADN does not affect PH induction using TXA2. Significant PA adventitia damage is associated with HR acceleration after PADN. Possible delayed effects of PADN on perivascular nerves and pulmonary hemodynamics require further research in chronic experiments.


Assuntos
Denervação/métodos , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/cirurgia , Artéria Pulmonar/fisiopatologia , Artéria Pulmonar/cirurgia , Animais , Pressão Sanguínea , Ablação por Cateter/métodos , Modelos Animais de Doenças , Hemodinâmica , Masculino , Suínos
11.
Int J Mol Sci ; 22(23)2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34884785

RESUMO

Drought is a major abiotic stress imposed by climate change that affects crop production and soil microbial functions. Plants respond to water deficits at the morphological, biochemical, and physiological levels, and invoke different adaptation mechanisms to tolerate drought stress. Plant growth-promoting bacteria (PGPB) can help to alleviate drought stress in plants through various strategies, including phytohormone production, the solubilization of mineral nutrients, and the production of 1-aminocyclopropane-1-carboxylate deaminase and osmolytes. However, PGPB populations and functions are influenced by adverse soil factors, such as drought. Therefore, maintaining the viability and stability of PGPB applied to arid soils requires that the PGPB have to be protected by suitable coatings. The encapsulation of PGPB is one of the newest and most efficient techniques for protecting beneficial bacteria against unfavorable soil conditions. Coatings made from polysaccharides, such as sodium alginate, chitosan, starch, cellulose, and their derivatives, can absorb and retain substantial amounts of water in the interstitial sites of their structures, thereby promoting bacterial survival and better plant growth.


Assuntos
Bactérias/metabolismo , Encapsulamento de Células/métodos , Secas , Desenvolvimento Vegetal/fisiologia , Raízes de Plantas/microbiologia , Polissacarídeos/metabolismo , Aclimatação/fisiologia , Alginatos/metabolismo , Carbono-Carbono Liases/metabolismo , Quitosana/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Plantas/microbiologia , Rizosfera , Microbiologia do Solo , Estresse Fisiológico/fisiologia
12.
Int J Mol Sci ; 22(20)2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34681825

RESUMO

One of the most favored trends in modern agriculture is biological control. However, many reports show that survival of biocontrol bacteria is poor in host plants. Providing biocontrol agents with protection by encapsulation within external coatings has therefore become a popular idea. Various techniques, including extrusion, spray drying, and emulsion, have been introduced for encapsulation of biocontrol bacteria. One commonly used biopolymer for this type of microencapsulation is alginate, a biopolymer extracted from seaweed. Recent progress has resulted in the production of alginate-based microcapsules that meet key bacterial encapsulation requirements, including biocompatibility, biodegradability, and support of long-term survival and function. However, more studies are needed regarding the effect of encapsulation on protective bacteria and their targeted release in organic crop production systems. Most importantly, the efficacy of alginate use for the encapsulation of biocontrol bacteria in pest and disease management requires further verification. Achieving a new formulation based on biodegradable polymers can have significant effects on increasing the quantity and quality of agricultural products.


Assuntos
Agricultura/métodos , Alginatos/química , Bactérias/crescimento & desenvolvimento , Agentes de Controle Biológico , Biotecnologia/métodos , Doenças das Plantas/microbiologia , Doenças das Plantas/terapia , Materiais Biocompatíveis , Biodegradação Ambiental , Biopolímeros/química , Cápsulas/química , Interações Microbianas , Viabilidade Microbiana , Desenvolvimento Vegetal
13.
Int J Mol Sci ; 22(20)2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34681619

RESUMO

The development of intravitreal glucocorticoid delivery systems is a current global challenge for the treatment of inflammatory diseases of the posterior segment of the eye. The main advantages of these systems are that they can overcome anatomical and physiological ophthalmic barriers and increase local bioavailability while prolonging and controlling drug release over several months to improve the safety and effectiveness of glucocorticoid therapy. One approach to the development of optimal delivery systems for intravitreal injections is the conjugation of low-molecular-weight drugs with natural polymers to prevent their rapid elimination and provide targeted and controlled release. This study focuses on the development of a procedure for a two-step synthesis of dexamethasone (DEX) conjugates based on the natural polysaccharide chitosan (CS). We first used carbodiimide chemistry to conjugate DEX to CS via a succinyl linker, and we then modified the obtained systems with succinic anhydride to impart a negative ζ-potential to the polymer particle surface. The resulting polysaccharide carriers had a degree of substitution with DEX moieties of 2-4%, a DEX content of 50-85 µg/mg, and a degree of succinylation of 64-68%. The size of the obtained particles was 400-1100 nm, and the ζ-potential was -30 to -33 mV. In vitro release studies at pH 7.4 showed slow hydrolysis of the amide and ester bonds in the synthesized systems, with a total release of 8-10% for both DEX and succinyl dexamethasone (SucDEX) after 1 month. The developed conjugates showed a significant anti-inflammatory effect in TNFα-induced and LPS-induced inflammation models, suppressing CD54 expression in THP-1 cells by 2- and 4-fold, respectively. Thus, these novel succinyl chitosan-dexamethasone (SucCS-DEX) conjugates are promising ophthalmic carriers for intravitreal delivery.


Assuntos
Anti-Inflamatórios/química , Quitosana/química , Dexametasona/química , Portadores de Fármacos/química , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Linhagem Celular , Dexametasona/metabolismo , Dexametasona/farmacologia , Liberação Controlada de Fármacos , Humanos , Lipopolissacarídeos/farmacologia , Monócitos/citologia , Monócitos/efeitos dos fármacos , Monócitos/metabolismo
14.
Int J Mol Sci ; 22(16)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34445088

RESUMO

Improving the therapeutic characteristics of antibiotics is an effective strategy for controlling the growth of multidrug-resistant Gram-negative microorganisms. The purpose of this study was to develop a colistin (CT) delivery system based on hyaluronic acid (HA) and the water-soluble cationic chitosan derivative, diethylaminoethyl chitosan (DEAECS). The CT delivery system was a polyelectrolyte complex (PEC) obtained by interpolymeric interactions between the HA polyanion and the DEAECS polycation, with simultaneous inclusion of positively charged CT molecules into the resulting complex. The developed PEC had a hydrodynamic diameter of 210-250 nm and a negative surface charge (ζ-potential = -19 mV); the encapsulation and loading efficiencies were 100 and 16.7%, respectively. The developed CT delivery systems were characterized by modified release (30-40% and 85-90% of CT released in 15 and 60 min, respectively) compared to pure CT (100% CT released in 15 min). In vitro experiments showed that the encapsulation of CT in polysaccharide carriers did not reduce its antimicrobial activity, as the minimum inhibitory concentrations against Pseudomonas aeruginosa of both encapsulated CT and pure CT were 1 µg/mL.


Assuntos
Antibacterianos/administração & dosagem , Quitosana/química , Colistina/administração & dosagem , Portadores de Fármacos/química , Ácido Hialurônico/química , Polieletrólitos/química , Antibacterianos/farmacologia , Colistina/farmacologia , Humanos , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos
15.
Int J Mol Sci ; 21(1)2019 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-31881739

RESUMO

A simple, low-cost, and reproducible method for creating materials with even silver nanoparticles (AgNP) dispersion was established. Chitosan nanofibers with silica phase (CS/silica) were synthesized by an electrospinning technique to obtain highly porous 3D nanofiber scaffolds. Silver nanoparticles in the form of a well-dispersed metallic phase were synthesized in an external preparation step and embedded in the CS/silica nanofibers by deposition for obtaining chitosan nanofibers with silica phase decorated by silver nanoparticles (Ag/CS/silica). The antibacterial activity of investigated materials was tested using Gram-positive and Gram-negative bacteria. The results were compared with the properties of the nanocomposite without silver nanoparticles and a colloidal solution of AgNP. The minimum inhibitory concentration (MIC) of obtained AgNP against Staphylococcus aureus (S. aureus) ATCC25923 and Escherichia coli (E. coli) ATCC25922 was determined. The physicochemical characterization of Ag/CS/silica nanofibers using various analytical techniques, as well as the applicability of these techniques in the characterization of this type of nanocomposite, is presented. The resulting Ag/CS/silica nanocomposites (Ag/CS/silica nanofibers) were characterized by small angle X-ray scattering (SAXS), X-ray diffraction (XRD), and atomic force microscopy (AFM). The morphology of the AgNP in solution, both initial and extracted from composite, the properties of composites, the size, and crystallinity of the nanoparticles, and the characteristics of the chitosan fibers were determined by electron microscopy (SEM and TEM).


Assuntos
Antibacterianos/química , Quitosana/química , Nanopartículas Metálicas/química , Nanofibras/química , Dióxido de Silício/química , Prata/química , Antibacterianos/farmacologia , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos
16.
J Mater Sci Mater Med ; 28(1): 21, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28012155

RESUMO

Chitosan scaffolds have gained much attention in various tissue engineering applications, but the effect of their microstructure on cell-material spatial interactions remains unclear. Our objective was to evaluate the effect of chitosan-based matrices doping with chitin nano-whiskers (CNW) on adhesion, spreading, cytoskeleton structure, and proliferation of rat bone marrow stromal cells (BMSCs). The behavior of BMSCs during culture on chitosan-CNW films was determined by the molecular mass, hydrophobicity, porosity, crosslinking degree, protonation degree and molecular structure of the composite chitosan-CNW films. The shape, spreading area, cytoskeleton structure, and proliferation of BMSCs on chitosan matrices with a crystalline structure and high porosity were similar to that observed for BMSCs cultured on polystyrene tissue culture plates. The amorphous polymer structure and high swelling led to a decrease in the spreading area and cell proliferation. Thus, we can control the behavior of cells in culture (adhesion, spreading, and proliferation) by changing the physico-chemical properties of the chitosan-CNW films.


Assuntos
Quitina/química , Quitosana/química , Citoesqueleto/química , Células-Tronco Mesenquimais/citologia , Nanofibras/química , Animais , Materiais Biocompatíveis/química , Proliferação de Células , Cristalização , Masculino , Polímeros/química , Poliestirenos/química , Porosidade , Ratos , Ratos Wistar , Reologia , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Viscosidade , Difração de Raios X
17.
Molecules ; 22(12)2017 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-29240705

RESUMO

Two-ply composite membranes with separation layers from chitosan and sulfoethylcellulose were developed on a microporous support based on poly(diphenylsulfone-N-phenylphthalimide) and investigated by use of X-ray diffraction and scanning electron microscopy methods. The pervaporation properties of the membranes were studied for the separation of aqueous alcohol (ethanol, propan-2-ol) mixtures of different compositions. When the mixtures to be separated consist of less than 15 wt % water in propan-2-ol, the membranes composed of polyelectrolytes with the same molar fraction of ionogenic groups (-NH3⁺ for chitosan and -SO3- for sulfoethylcellulose) show high permselectivity (the water content in the permeate was 100%). Factors affecting the structure of a non-porous layer of the polyelectrolyte complex formed on the substrate surface and the contribution of that complex to changes in the transport properties of membranes are discussed. The results indicate significant prospects for the use of chitosan and sulfoethylcellulose for the formation of highly selective pervaporation membranes.


Assuntos
Celulose/análogos & derivados , Celulose/química , Quitosana/química , Membranas Artificiais , Ftalimidas/química , Sulfonas/química , 2-Propanol/isolamento & purificação , Etanol/isolamento & purificação , Estrutura Molecular , Polímeros/química , Porosidade , Relação Estrutura-Atividade , Propriedades de Superfície , Água/química
18.
Biomacromolecules ; 17(11): 3493-3507, 2016 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-27636143

RESUMO

Here, we present the synthesis, physicochemical, and preliminary biological characterization of micellar polymer-betulinic acid (BA) conjugates based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer carriers, enabling the controlled release of cytotoxic BA derivatives in solid tumors or tumor cells. Various HPMA copolymer conjugates differing in the structure of the spacer between the drug and the carrier were synthesized, all designed for pH-triggered drug release in tumor tissue or tumor cells. The high molecular weight of the micellar conjugates should improve the uptake of the drug in solid tumors due to the Enhanced permeability and retention (EPR) effect. Nevertheless, only the conjugate containing BA with methylated carboxyl groups enabled pH-dependent controlled release in vitro. Moreover, drug release led to the disassembly of the micellar structure, which facilitated elimination of the water-soluble HPMA copolymer carrier from the body by renal filtration. The methylated BA derivative and its polymer conjugate exhibited high cytostatic activity against DLD-1, HT-29, and HeLa carcinoma cell lines and enhanced tumor accumulation in HT-29 xenograft in mice.


Assuntos
Proliferação de Células/efeitos dos fármacos , Doxorrubicina/química , Metacrilatos/química , Neoplasias/tratamento farmacológico , Animais , Plásticos Biodegradáveis/química , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Humanos , Metacrilatos/administração & dosagem , Camundongos , Micelas , Triterpenos Pentacíclicos , Polímeros/administração & dosagem , Polímeros/química , Triterpenos/administração & dosagem , Triterpenos/química , Ácido Betulínico
19.
Carbohydr Polym ; 337: 122145, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38710553

RESUMO

Hyaluronic acid (HA) has emerged as a promising biopolymer for various biomedical applications due to its biocompatibility, biodegradability, and intrinsic ability to interact with cell surface receptors, making it an attractive candidate for drug delivery systems and tissue engineering. Chemical modification of HA has opened up versatile possibilities to tailor its properties, enabling the development of advanced drug delivery systems and biomaterials with enhanced functionalities and targeted applications. This review analyzes the strategies and applications of chemically modified HA in the field of drug delivery and biomaterial development. The first part of the review focuses on the different methods and functional groups used for the chemical modification of HA, highlighting the impact of these modifications on its physicochemical properties, degradation behavior and interactions with drugs. The second part of the review evaluates the use of chemically modified HA in the development of advanced biomedical materials including nano- and microparticles, hydrogels and mucoadhesive materials with tailored drug release profiles, site-specific targeting and stimuli-responsive behavior. Thus, the review consolidates the current advances and future perspectives in the field of chemical modification of HA, underscoring its immense potential to drive the development of advanced drug delivery systems and biomaterials with diverse biomedical applications.


Assuntos
Materiais Biocompatíveis , Sistemas de Liberação de Medicamentos , Ácido Hialurônico , Hidrogéis , Ácido Hialurônico/química , Humanos , Sistemas de Liberação de Medicamentos/métodos , Materiais Biocompatíveis/química , Hidrogéis/química , Animais , Liberação Controlada de Fármacos , Portadores de Fármacos/química , Engenharia Tecidual/métodos , Nanopartículas/química
20.
Int J Biol Macromol ; 263(Pt 1): 130177, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38360229

RESUMO

Polyelectrolyte complexes (PECs) based on polysaccharides, including hyaluronic acid (HA) and chitosan (CS), are promising delivery systems for antimicrobial agents, including oral administration of the peptide antibiotic colistin (CT). Modification of CS with different targeting ligands to improve intestinal permeability is a suitable way to improve the oral bioavailability of polyelectrolyte particles. This study describes the procedure for obtaining CT-containing PECs based on HA and CS modified with cyanocobalamin (vitamin B12). In this case, vitamin B12 is used as a targeting ligand because it is absorbed in the ileum via specific transporter proteins. The resulting PECs had a hydrodynamic size of about 284 nm and a positive ζ-potential of about 26 mV; the encapsulation efficiency was 88.2 % and the CT content was 42.2 µg/mg. The developed systems provided a two-phase drug release: about 50 % of the CT was released in 0.5-1 h, and about 60 % of the antibiotic was cumulatively released in 5 h. The antimicrobial activity of encapsulated CT was maintained at the same level as the pure drug for at least 24 h (minimum inhibitory concentration against Pseudomonas aeruginosa was 2 µg/mL for both). In addition, the apparent permeability coefficient of CT in the PEC formulation was 2.4 × 10-6 cm/s. Thus, the incorporation of CT into HA- and vitamin B12-modified CS-based PECs can be considered as a simple and convenient method to improve the oral delivery of CT.


Assuntos
Quitosana , Polieletrólitos/química , Quitosana/química , Portadores de Fármacos/química , Ácido Hialurônico , Colistina/farmacologia , Vitamina B 12 , Administração Oral , Antibacterianos/farmacologia
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