RESUMO
Herein, dexamethasone (DEX) nanocrystalline suspension (NS)-embedded hydrogel (NS-G) was constructed using a hydroxypropyl methylcellulose (HPMC) polymer to enhance cochlear delivery and attenuate hearing loss following intratympanic (IT) injection. Hydrophobic steroidal nanocrystals were prepared using a bead milling technique and incorporated into a polysaccharide hydrogel. The NS-G system with HPMC (average molecular weight, 86,000 g/mol; 15 mg/mL) was characterized as follows: rod-shaped drug crystalline; particle size <300 nm; and constant complex viscosity ≤1.17 Pa·s. Pulverization of the drug particles into submicron diameters enhanced drug dissolution, while the HPMC matrix increased the residence time in the middle ear cavity, exhibiting a controlled release profile. The IT NS-G system elicited markedly enhanced and prolonged drug delivery (> 9 h) to the cochlear tissue compared with that of DEX sodium phosphate (DEX-SP), a water-soluble prodrug. In mice with kanamycin- and furosemide-induced ototoxicity, NS-G markedly enhanced hearing preservation across all frequencies (8-32 kHz), as revealed by an auditory brainstem response test, compared with both saline and DEX-SP. Moreover, treatment with NS-G showed enhanced anti-inflammatory effects, as evidenced by decreased levels of inflammation-related cytokines. Therefore, the IT administration of DEX NS-loaded HPMC hydrogels is a promising strategy for treating hearing loss.
Assuntos
Cóclea , Dexametasona , Perda Auditiva , Hidrogéis , Derivados da Hipromelose , Injeção Intratimpânica , Nanopartículas , Dexametasona/química , Dexametasona/administração & dosagem , Animais , Derivados da Hipromelose/química , Hidrogéis/química , Nanopartículas/química , Camundongos , Cóclea/efeitos dos fármacos , Cóclea/patologia , Perda Auditiva/tratamento farmacológico , Perda Auditiva/induzido quimicamente , Liberação Controlada de Fármacos , Masculino , Sistemas de Liberação de Medicamentos/métodosRESUMO
The requirement to improve the efficiency of pesticide utilization has led to the development of sustainable and smart stimuli-responsive pesticide delivery systems. Herein, a novel avermectin nano/micro spheres (AVM@HPMC-Oxalate) with sensitive stimuli-response function target to the Lepidoptera pests midgut microenvironment (pH 8.0-9.5) was constructed using hydroxypropyl methylcellulose (HPMC) as the cost-effective and biodegradable material. The avermectin (AVM) loaded nano/micro sphere was achieved with high AVM loading capacity (up to 66.8 %). The simulated release experiment proved the rapid stimuli-responsive and pesticides release function in weak alkaline (pH 9) or cellulase environment, and the release kinetics were explained through release models and SEM characterization. Besides, the nano/micro sphere size made AVM@HPMC-Oxalate has higher foliar retention rate (1.6-2.1-fold higher than commercial formulation) which is beneficial for improving the utilization of pesticides. The in vivo bioassay proved that AVM@HPMC-Oxalate could achieve the long-term control of Plutella xylostella by extending UV shielding performance (9 fold higher than commercial formulation). After 3 h of irradiation, the mortality rate of P. xylostella treated by AVM@HPMC-Oxalate still up to 56.7 % ± 5.8 %. Moreover, AVM@HPMC-Oxalate was less toxic to non-target organisms, and the acute toxicity to zebrafish was reduced by 2-fold compared with AVM technical.
Assuntos
Ivermectina , Mariposas , Raios Ultravioleta , Ivermectina/análogos & derivados , Ivermectina/química , Ivermectina/farmacologia , Ivermectina/toxicidade , Animais , Mariposas/efeitos dos fármacos , Inseticidas/química , Inseticidas/farmacologia , Inseticidas/toxicidade , Celulose/química , Celulose/análogos & derivados , Derivados da Hipromelose/química , Concentração de Íons de Hidrogênio , Liberação Controlada de FármacosRESUMO
This research aims to produce orodispersible films (ODFs) and determine their potential use in the oral delivery of montelukast sodium for asthma treatment and allergic rhinitis. ODFs were successfully developed by Three-dimensional (3D) printing using propylene glycol (PG), and hydroxypropyl methylcellulose (HPMC), polyethylene glycol 400 (PEG). Finally, the amount of montelukast sodium in the ODFs was 5% (w/w). Drug-excipients compatibility with Fourier Transformed Infrared (FTIR) spectroscopy, mass uniformity, thickness, disintegration time, folding endurance, moisture absorption, pH, in vitro drug release (dissolution), drug content, moisture loss, moisture content, mechanical properties, and cytotoxicity studies were performed on the prepared films. All formulations disintegrated in approximately 40 s. Over 98% of drug release from all films within 2 min was confirmed. It was reported that Fm1-4 (8% HPMC and 1% PEG) and Fm2-4 (10% HPMC and 3% PEG) are more suitable for drug content, but Fm2-4 may be the ideal formulation considering its durability and transportability properties. Based on the characterization results and in vitro release values, the montelukast sodium ODF can be an option for other dosage forms. It was concluded that the formulations did not show toxic potential by in vitro cytotoxicity study with 3T3 cells. This new formulation can efficiently treat allergic rhinitis and asthma diseases.
Assuntos
Acetatos , Antiasmáticos , Asma , Ciclopropanos , Liberação Controlada de Fármacos , Polietilenoglicóis , Impressão Tridimensional , Quinolinas , Sulfetos , Ciclopropanos/administração & dosagem , Quinolinas/administração & dosagem , Quinolinas/química , Acetatos/química , Acetatos/administração & dosagem , Sulfetos/química , Asma/tratamento farmacológico , Polietilenoglicóis/química , Administração Oral , Antiasmáticos/administração & dosagem , Antiasmáticos/química , Antiasmáticos/farmacologia , Animais , Excipientes/química , Camundongos , Sistemas de Liberação de Medicamentos/métodos , Química Farmacêutica/métodos , Derivados da Hipromelose/química , Propilenoglicol/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , SolubilidadeRESUMO
The focus of the present work was to develop amorphous solid dispersion (ASD) formulation of aprepitant (APT) using sucrose acetate isobutyrate (SAIB) excipient, evaluate for physicochemical attributes, stability, and bioavailability, and compared with hydroxypropyl methylcellulose (HPMC) based formulation. Various formulations of APT were prepared by solvent evaporation method and characterized for physiochemical and in-vivo performance attributes such as dissolution, drug phase, stability, and bioavailability. X-ray powder diffraction indicated crystalline drug conversion into amorphous phase. Dissolution varied as a function of drug:SAIB:excipient proportion. The dissolution was more than 80% in the optimized formulation (F10) and comparable to HPMC based formulation (F13). Stability of F10 and F13 formulations stored at 25 C/60% and 40°C/75% RH for three months were comparable. Both ASD formulations (F10 and F13) were bioequivalent as indicated by the pharmacokinetic parameters Cmax and AUC0-∞. Cmax and AUC0-∞ of F10 and F13 formulations were 2.52 ± 0.39, and 2.74 ± 0.32 µg/ml, and 26.59 ± 0.39, and 24.79 ± 6.02 µg/ml.h, respectively. Furthermore, the bioavailability of ASD formulation was more than twofold of the formulation containing crystalline phase of the drug. In conclusion, stability and oral bioavailability of SAIB based ASD formulation is comparable to HPMC-based formulation of poorly soluble drugs.
Assuntos
Disponibilidade Biológica , Excipientes , Solubilidade , Sacarose , Sacarose/análogos & derivados , Sacarose/química , Administração Oral , Animais , Excipientes/química , Masculino , Derivados da Hipromelose/química , Química Farmacêutica/métodos , Estabilidade de Medicamentos , Difração de Raios X/métodosRESUMO
Oral conditions, such as recurrent aphthous stomatitis, are chronic inflammatory disorders that significantly affect the life quality. This study aims to develop a novel buccal mucoadhesive based on methacrylate hydroxypropyl methylcellulose (M-HPMC) and methacrylate lignin (M-SLS) encapsulated with nanostructured lipid carriers (NLCs) for controlled release of alpha-pinene (α-pinene). NLCs with particle sizes of 152 ± 3 nm were prepared by using stearic acid and oleic acid as solid and liquid lipids, respectively. Following the successful synthesis of M-HPMC and M-SLS, various concentrations of α-pinene loaded NLCs (0, 18, 38, and 50 wt%) were encapsulated in M-HPMC/M-SLS hydrogel. It was demonstrated that the physiological and mechanical performances of hydrogels were changed, depending on the NLC content. Remarkably, the incorporation of 18 wt% NLC improved the compressive strength (143 ± 14 kPa) and toughness (17 ± 1 kJ/m3) of M-HPMC/M-SLS hydrogel. This nanocomposite hydrogel considerably decreased dissipated energy from 1.64 kJ/m3 to 0.99 kJ/m3, after a five-cycle compression test. The nanocomposite hydrogel exhibited controlled α-pinene release for up to 96 h which could significantly improve the antioxidant activity of M-HPMC/M-SLS matrix. Moreover, the reinforcing M-HPMC/M-SLS hydrogel with α-pinene-loaded NLCs resulted in increased adhesive strength (113.5 ± 7.5 kPa) to bovine buccal mucosa and cytocompatibility in contact with fibroblasts.
Assuntos
Monoterpenos Bicíclicos , Hidrogéis , Derivados da Hipromelose , Lignina , Nanocompostos , Lignina/química , Monoterpenos Bicíclicos/química , Monoterpenos Bicíclicos/farmacologia , Hidrogéis/química , Hidrogéis/síntese química , Hidrogéis/farmacologia , Nanocompostos/química , Animais , Derivados da Hipromelose/química , Camundongos , Metacrilatos/química , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/síntese química , Antioxidantes/administração & dosagem , Fibroblastos/efeitos dos fármacosRESUMO
Vitiligo is a significant dermatological challenge affecting 0.5 to 2% of the global population. Despite the various existing medical approaches, current vitiligo treatments are far from ideal. The present study aimed to prepare and evaluate a film-forming gel of 5 fluorouracil (5FU) using different ratios of hydroxypropyl methylcellulose (HPMC) and Zein for treating vitiligo. The prepared film-forming gels were fully characterized in terms of morphology, Fourier-transform infrared spectroscopy, drug content, pH, drying time, in-vitro drug release, and clinical investigation. A 32-full factorial design was used to study the impact of varying concentrations of HPMC (X1) and Zein (X2) on the percentage of 5FU released (Y1) from the prepared film-forming gels. Scanning electron microscopy (SEM) revealed a cross-linked network structure between polymers. An increase in HPMC concentration (2-4%) correlated with higher 5FU release, whereas increased Zein concentration (1-2%) resulted in reduced 5FU release. Furthermore, patients treated with 5FU film-forming gel after dermabrasion with fractional CO2 (FCO2) laser exhibited a significant decrease in JAK3 gene expression and higher effectiveness than those treated with FCO2 laser alone. Our results suggest that the film-forming gel of 5FU is promising as an effective formulation for treating vitiligo.
Assuntos
Fluoruracila , Géis , Derivados da Hipromelose , Lasers de Gás , Vitiligo , Zeína , Fluoruracila/administração & dosagem , Vitiligo/tratamento farmacológico , Vitiligo/terapia , Zeína/química , Derivados da Hipromelose/química , Humanos , Liberação Controlada de Fármacos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , MasculinoRESUMO
Effective sedative drugs are in great demand due to increasing incidence of nervous disorders. The present work was aimed to develop a novel sublingual sedative drug based on glycine and L-tryptophan amino acids. Carbopol and different hydroxypropyl methylcellulose species were alternatively tested as mucoadhesive agents intended to prolong tryptophan sublingual release time. A model lipid medium of fully hydrated L-α-dimyristoylphosphatidylcholine was used for optimal mucoadhesive agents selection. Simultaneous processes of drug release and diffusion in lipid medium were first investigated involving both experimental and theoretical approaches. Individual substances, their selected combinations as well as different drug formulations were consecutively examined. Application of kinetic differential scanning calorimetry method allowed us to reveal a number of specific drug-excipient effects. Lactose was found to essentially facilitate tryptophan release and provide its ability to get into the bloodstream simultaneously with glycine, which is necessary to achieve glycine-tryptophan synergism. Introduction of a mucoadhesive agent into the formulation was shown to change kinetics of drug-membrane interactions variously depending on viscosity grade. Among the mucoadhesive agents, hydroxypropyl methylcellulose species K4M and E4M were shown to further accelerate drug release, therefore they were selected as optimal. Thus, effectiveness of the novel sedative drug was provided by including some excipients, such as lactose and the selected mucoadhesive agent species. A dynamic mathematical model was developed properly describing release and diffusion in lipid medium of various drug substances. Our study clearly showed applicability of a lipid medium to meet challenges such as drug-excipient interactions and optimization of drug formulations.
Assuntos
Excipientes , Glicina , Hipnóticos e Sedativos , Triptofano , Triptofano/química , Triptofano/administração & dosagem , Glicina/química , Glicina/administração & dosagem , Administração Sublingual , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/química , Hipnóticos e Sedativos/farmacocinética , Excipientes/química , Liberação Controlada de Fármacos , Química Farmacêutica/métodos , Varredura Diferencial de Calorimetria , Lactose/química , Derivados da Hipromelose/química , Biofarmácia/métodos , Adesividade , ViscosidadeRESUMO
The compound Salvia Recipe has been shown to have a relatively significant curative effect in management of cardiovascular and cerebrovascular diseases. This work aimed to prepare a thermosensitive in situ gel (ISG) delivery system that utilizes Poloxamer 407, Poloxamer 188, and hydroxypropyl methylcellulose for ocular administration of the compound Salvia recipe to treat cardiovascular and cerebrovascular diseases. The central composite design-response surface method was utilized to improve the prescription of the gel. The formulated gel was characterized and assessed in terms of stability, retention time, in vitro release, rheology, ocular irritation, pharmacokinetics studies, and tissue distribution. The gel was a liquid solution at room temperature and became semisolid at physiological temperature, prolonging its stay time in the eye. Pharmacokinetics and tissue distribution experiments indicated that thermosensitive ISG had enhanced targeting of heart and brain tissues. Additionally, it could lower drug toxicity and side effects in the lungs and kidneys. The compound Salvia ophthalmic thermosensitive ISG is a promising drug delivery system for the management of cardiovascular and cerebrovascular illnesses.
Assuntos
Administração Oftálmica , Sistemas de Liberação de Medicamentos , Géis , Salvia , Animais , Salvia/química , Sistemas de Liberação de Medicamentos/métodos , Distribuição Tecidual , Temperatura , Poloxâmero/química , Coelhos , Olho/efeitos dos fármacos , Olho/metabolismo , Química Farmacêutica/métodos , Derivados da Hipromelose/química , Masculino , Reologia , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinéticaRESUMO
Low-viscosity hydroxypropyl methylcellulose (HPMC) was obtained by electron beam irradiation, and its use as an excipient for improving the properties of spray dried pharmaceutical powders was investigated. The minimum molecular weight of HPMC which could maintain the capacity of encapsulation and powder modification was explored. As the irradiation dose was increased from 10 to 200 kGy, the molecular weight and viscosity of HPMC decreased linearly. However, its main structure and degrees of methoxy and hydroxypropyl substitution were not significantly affected. The irradiated HPMC could encapsulate particles during spray drying and, thus, modify powder properties. Furthermore, the water content of spray-dried powders with irradiated HPMC was lower than that with parent HPMC. After the spray-dried powder with irradiated HPMC was prepared into granules, their dissolution rate was also faster. However, in order to achieve high encapsulation, the molecular weight of HPMC should be ensured to be above 7.5 kDa. The designated low-viscosity HPMC obtained by electron beam irradiation is a suitable powder-modification material for use in spray drying, and it shows promise as a superior excipient in medicine, food, paint industries, among others.
Assuntos
Elétrons , Derivados da Hipromelose , Peso Molecular , Secagem por Atomização , Derivados da Hipromelose/química , Viscosidade , Pós , Tamanho da Partícula , Excipientes/química , Água/químicaRESUMO
In this study, berberine hydrochloride (Ber) was used as model drug to prepare a sustained-release cold sol using hydroxypropyl methyl cellulose (HPMC) to achieve superior drug dissolution and transdermal absorption effects. For comparison, a Ber cold sol without HPMC was also prepared using the same method. The preparation process was optimized based on the in vitro release and transdermal permeability of the drug. The results indicated that 1.67 wt% Carbomer 940 and 1.33 wt% HPMC K100M were selected as matrix components with the best sustained-release effect, and drug dissolution of cold sol prepared by combination of these two matrices was significantly slower than the cold sol without HPMC. In addition, transdermal absorption result demonstrated that 0.67 wt% glycerin and 1.33 wt% peppermint oil were the best osmotic enhancers for the optimization of Ber sustained-release cold sol. Herein, HPMC K100M performed important functions in the external application of Ber.
Assuntos
Berberina , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Derivados da Hipromelose , Absorção Cutânea , Solubilidade , Berberina/farmacocinética , Berberina/química , Berberina/administração & dosagem , Berberina/farmacologia , Derivados da Hipromelose/química , Absorção Cutânea/efeitos dos fármacos , Animais , Administração CutâneaRESUMO
Due to their potential adverse health effects, some N-nitrosamines in drug products are strictly regulated with very low maximum daily intake limits. Nitrosamines can be formed from the reaction of nitrite and secondary or tertiary amines when both species co-exist in the drug synthesis or formulation process. One key strategy to mitigate nitrosamine risk in drugs is to select low-nitrite containing pharma excipients for formulation. It is necessary to develop a sensitive method for trace nitrite determination in pharma excipients as it enables drug producers to study nitrosamine formation kinetics and select excipient suppliers. This study details the development and validation of a two-dimensional ion chromatography mass spectrometry (2D-IC/MS) method for trace nitrite determination in hydroxypropyl methylcellulose (HPMC), one of the most important pharmaceutical excipients used in many drug formulations. The 2D-IC system was operated in heart-cutting mode with a concentrator column coupling the two dimensions. A standard bore anion-exchange column was used in the first dimension (1D) to enable a large volume injection for increased sensitivity and provide improved resolution between nitrite and the interfering chloride peak. A high efficiency microbore anion-exchange column with different selectivity was used in the second dimension (2D) to resolve nitrite from other interfering species. The use of 2D-IC resulted in significantly improved resolution, solving the sensitivity loss issue due to ion suppression from an otherwise 1D separation. MS detection with selective ion monitoring and isotope labeled nitrite internal standard further improve the method specificity, accuracy, and ruggedness, as compared with conductivity detection. For trace determination, it is also extremely important to have a clean blank. For this purpose, a novel cleaning procedure using a strong anion wash was developed to remove nitrite contamination from labware. The optimized method was validated with linearity of nitrite in the concentration range of 18.5-5005.8â¯ng/g having a regression coefficient of >0.9999, precision with RSD at 3.5-10.1â¯% and recovery of 90.5-102.4â¯%. The limit of detection and limit of quantitation were 8.9 and 29.6â¯ng/g relative to the HPMC sample, or equivalent to 89 and 296â¯pg/g in the sample solution, respectively.
Assuntos
Derivados da Hipromelose , Nitritos , Nitritos/análise , Derivados da Hipromelose/química , Cromatografia por Troca Iônica/métodos , Espectrometria de Massas/métodos , Reprodutibilidade dos Testes , Excipientes/química , Excipientes/análise , Nitrosaminas/análise , Nitrosaminas/química , Limite de DetecçãoRESUMO
Microparticles as a multicompartment drug delivery system are beneficial for poorly soluble drugs. Mucoadhesive polymers applied in microparticle technology prolong the contact of the drug with the mucosa surface enhancing drug bioavailability and extending drug activity. Sodium alginate (ALG) and hydroxypropyl methylcellulose (hypromellose, HPMC) are polymers of a natural or semi-synthetic origin, respectively. They are characterized by mucoadhesive properties and are applied in microparticle technology. Spray drying is a technology employed in microparticle preparation, consisting of the atomization of liquid in a stream of gas. In this study, the pharmaceutical properties of spray-dried ALG/HPMC microparticles with posaconazole were compared with the properties of physical mixtures of powders with equal qualitative and quantitative compositions. Posaconazole (POS) as a relatively novel antifungal was utilized as a model poorly water-soluble drug, and hard gelatin capsules were applied as a reservoir for designed formulations. A release study in 0.1 M HCl showed significantly prolonged POS release from microparticles compared to a mixture of powders. Such a relationship was not followed in simulated vaginal fluid (SVF). Microparticles were also characterized by stronger mucoadhesive properties, an increased swelling ratio, and prolonged residence time compared to physical mixtures of powders. The obtained results indicated that the pharmaceutical properties of hard gelatin capsules filled with microparticles were significantly different from hard gelatin capsules with mixtures of powders.
Assuntos
Alginatos , Cápsulas , Sistemas de Liberação de Medicamentos , Gelatina , Derivados da Hipromelose , Triazóis , Alginatos/química , Gelatina/química , Derivados da Hipromelose/química , Sistemas de Liberação de Medicamentos/métodos , Triazóis/química , Triazóis/administração & dosagem , Triazóis/farmacocinética , Liberação Controlada de Fármacos , Preparações de Ação Retardada/química , Antifúngicos/administração & dosagem , Antifúngicos/química , Antifúngicos/farmacocinética , MicroesferasRESUMO
This study aimed to develop a thermosensitive in situ gel formulation for rectal delivery of Ibuprofen as an efficient alternative dosage form. Utilizing poloxamer 188, poloxamer 407, and HPMC via cold technique method, a thermosensitive in situ gel was successfully prepared. The concentration of Ibuprofen in the formulations was 1.2 % (w/w). The prepared gels underwent assessment for clarity, gelation temperature, gelation time, gel strength, spread ability, syringe-ability, pH, viscosity, FTIR, and drug content. The selected formulations exhibited a gelation temperature within the range of 30 °C to 36 °C, with consistent amount of drug soluble in the formulations (93 % - 110 %). Mucoadhesive studies, in vitro release tests, ex vivo modeling of drug release, kinetic studies modeling, and histopathology testing were also conducted. The formulation comprising 18 % poloxamer 407, 12 % poloxamer 188, and 1 % sodium chloride (FS15) demonstrated suitable gelation temperature and desirable drug release rate. In vitro drug release tests indicated completion within one hour for both FS10 (20 % P407 & 10 % P188) and FS15 (18 % P407 & 12 % P188), with consistent and predictable release patterns observed through kinetic modeling analysis. Microscopic histopathology examination confirmed the safety of the selected formula, exhibiting no irritation in the mucosal membrane of the sheep. In conclusion, Ibuprofen thermosensitive in situ gel presents a promising and convenient strategy as a rectal carrier and an alternative dosage form to solid suppositories.
Assuntos
Administração Retal , Anti-Inflamatórios não Esteroides , Liberação Controlada de Fármacos , Géis , Ibuprofeno , Poloxâmero , Ibuprofeno/química , Ibuprofeno/administração & dosagem , Ibuprofeno/farmacocinética , Géis/química , Animais , Poloxâmero/química , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacocinética , Temperatura , Viscosidade , Ovinos , Derivados da Hipromelose/químicaRESUMO
Since the local treatment of oral candidiasis usually requires long-term administration of the antifungal drug, an ideal dosage form should be able to maintain the drug release over an extended period, assuring an adequate concentration at the infection site. In this context, we have considered the possibility of a buccal delivery of miconazole nitrate (MN) by mucoadhesive polymeric matrices. The loading of the antifungal drug in a hydrophilic matrix was made possible by taking advantage of the amphiphilic nature of liposomes (LP). The MN-loaded LP were prepared by a thin film evaporation method followed by extrusion, while solid matrices were obtained by freeze-drying a suspension of the LP in a polymeric solution based on chitosan (CH), sodium hyaluronate (HYA), or hydroxypropyl methylcellulose (HPMC). MN-loaded LP measured 284.7 ± 20.1 nm with homogeneous size distribution, adequate drug encapsulation efficiency (86.0 ± 3.3 %) and positive zeta potential (+47.4 ± 3.3). CH and HYA-based formulations almost completely inhibited C. albicans growth after 24 h, even if the HYA-based one released a higher amount of the drug. The CH-based matrix also provided the best mucoadhesive capacity and therefore represents the most promising candidate for the local treatment of oral candidiasis.
Assuntos
Antifúngicos , Candida albicans , Candidíase Bucal , Quitosana , Liberação Controlada de Fármacos , Derivados da Hipromelose , Lipossomos , Miconazol , Antifúngicos/administração & dosagem , Antifúngicos/química , Antifúngicos/farmacocinética , Miconazol/administração & dosagem , Miconazol/química , Miconazol/farmacocinética , Candidíase Bucal/tratamento farmacológico , Candida albicans/efeitos dos fármacos , Derivados da Hipromelose/química , Administração Bucal , Quitosana/química , Quitosana/administração & dosagem , Adesividade , Ácido Hialurônico/química , Ácido Hialurônico/administração & dosagem , Polímeros/química , Sistemas de Liberação de Medicamentos , Mucosa Bucal/metabolismo , Mucosa Bucal/microbiologiaRESUMO
Diabetes-related slow healing of wounds is primarily driven by bacterial infections and angiogenesis disorder and presents a substantial hurdle in clinical treatment. To solve the above problems, an advanced multifunctional hydrogel system based on natural polymer was created here to facilitate wound healing in patients with chronic diabetes. The prepared dressing was composed of an outer hydrogel containing polyvinyl alcohol and hydroxypropyl methyl cellulose in dimethyl sulfoxide and water as binary solvents, and an inner hydrogel containing chitosan quaternary ammonium salt, flaxseed gum, and polyvinyl alcohol. Thus, a polysaccharide based bilayer hydrogel (BH) with superior mechanical strength and biocompatibility was created. This bilayer hydrogel could easily bind to dynamic tissue surfaces, thereby generating a protective barrier. Meanwhile, L-arginine-modified polyoxometalate (POM@L-Arg) nanoclusters were loaded in the inner hydrogel. They released NO when stimulated by the peroxide microenvironment of diabetic wounds. NO as a signal molecule regulated vascular tension and promoted cell proliferation and migration. Additionally, because of the synergistic effect of NO and the chitosan quaternary ammonium salt, the hydrogel system exhibited excellent antibacterial performance. The NO released reduced the levels of proinflammatory factors IL-6 and TNF-α in the diabetic wounds, which thus accelerated wound healing. In short, BH + POM@L-Arg is expected to serve as an ideal wound dressing as it exerts a good promotion effect on diabetes-related wound healing.
Assuntos
Antibacterianos , Arginina , Hidrogéis , Derivados da Hipromelose , Compostos de Tungstênio , Cicatrização , Cicatrização/efeitos dos fármacos , Arginina/química , Arginina/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Compostos de Tungstênio/química , Compostos de Tungstênio/farmacologia , Derivados da Hipromelose/química , Bandagens , Masculino , Humanos , Quitosana/química , Quitosana/farmacologia , Proliferação de Células/efeitos dos fármacos , Camundongos , Diabetes Mellitus Experimental/tratamento farmacológico , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVES: The permeability of triamcinolone acetonide (TA), from bilayer mucoadhesive buccal films, through a biomimetic membrane, Permeapad™, was investigated employing Franz diffusion cell. The delivery systems composition and ethyl cellulose (EC) backing layer, on drug permeability, were assessed. METHODS: Three TA-loaded films were tested; hydroxypropyl methylcellulose (HPMC K4M; bilayer [F1] and monolayer), HPMC K4M/Polyvinylpyrrolidone (PVP): 90/10 [F2], and HPMC K15M film [F3]. All films contained propylene glycol (PG-plasticiser). TA solution alone was used as a control. TA permeability via a Permeapad™ barrier, simulating buccal mucosa, was assessed over 8 h using a Franz diffusion cell. TA permeated into the receptor compartment, released in the donor compartment, and located on/within the Permeapad™ barrier were analysed using UV-spectrophotometer. RESULTS: 45.7 % drug retention within the Permeapad™ barrier was delivered from F1 (highest). F1, F2, and F3 significantly improved the TA's permeability through Permeapad™, compared to TA solution alone (e.g., 8.5 % TA-solution, 21.5 %-F1), attributed to the synergy effect of HPMC and propylene glycol acting as penetration enhancers. F1 displayed a significant increase in drug permeability (receptor compartment; 21.5 %) compared to F3 (17.0 %). PVP significantly enhanced drug permeability (27.5 %). Impermeable EC backing layer controlled unidirectional drug release and reduced drug loss into the donor compartment (e.g., â¼28 % for monolayer film to â¼10 % for bilayer film, F1). SIGNIFICANCE: The mucoadhesive films demonstrated improved TA permeability via Permeapad™. The findings suggest that these bilayer mucoadhesive films, particularly F1, hold promise for the effective topical treatment of oral mucosa disorders, such as recurrent aphthous stomatitis and oral lichen planus.
Assuntos
Mucosa Bucal , Permeabilidade , Povidona , Triancinolona Acetonida , Triancinolona Acetonida/química , Triancinolona Acetonida/farmacocinética , Mucosa Bucal/metabolismo , Povidona/química , Sistemas de Liberação de Medicamentos , Derivados da Hipromelose/química , Propilenoglicol/química , Celulose/análogos & derivados , Celulose/química , Administração BucalRESUMO
Recent work has shown that an amorphous drug-polymer salt can be highly stable against crystallization under hot and humid storage conditions (e.g., 40 °C/75% RH) and provide fast release and that these advantages depend on the degree of salt formation. Here, we investigate the salt formation between the basic drug lumefantrine (LMF) and several acidic polymers: poly(acrylic acid) (PAA), hypromellose phthalate (HPMCP), hypromellose acetate succinate (HPMCAS), cellulose acetate phthalate (CAP), Eudragit L100, and Eudragit L100-55. Salt formation was performed by "slurry synthesis" where dry components were mixed at room temperature in the presence of a small quantity of an organic solvent, which was subsequently removed. This method achieved more complete salt formation than the conventional methods of hot-melt extrusion and rotary evaporation. The acidic group density of a polymer was determined by nonaqueous titration in the same solvent used for slurry synthesis; the degree of LMF protonation was determined by X-ray photoelectron spectroscopy. The polymers studied show very different abilities to protonate LMF when compared at a common drug loading, following the order PAA > (HPMCP â¼ CAP â¼ L100 â¼ L100-55) > HPMCAS, but the difference largely disappears when the degree of protonation is plotted against the concentration of the available acidic groups for reaction. This indicates that the extent of salt formation is mainly controlled by the acidic group density and is less sensitive to the polymer architecture. Our results are relevant for selecting the optimal polymer to control the degree of ionization in amorphous solid dispersions.
Assuntos
Polímeros , Polímeros/química , Metilcelulose/química , Metilcelulose/análogos & derivados , Cristalização/métodos , Celulose/química , Celulose/análogos & derivados , Resinas Acrílicas/química , Sais/química , Derivados da Hipromelose/química , SolubilidadeRESUMO
This paper reports a novel α-gel formulation technology referred to as polymer complexed lamella (PCL) that uses hydroxypropyl methyl cellulose (HPMC) and glycerol. The PCL method suppressed lipid crystallization even after drying. This effect was maximized by the addition of HPMC and glycerol at high temperature. HPMC and lipids coexisted when mixed at high temperature, which decreased the mobility of HPMC, an effect that was enhanced by the strong interaction of glycerol with HPMC. These results indicate that mixing of HPMC with glycerol directly regulates the lipid structure and suppresses crystallization. PCL also maintained the effect of occlusion related to the moisturization of skin, even if the membrane was repeatedly bent such as in facial expressions.
Assuntos
Cristalização , Géis , Glicerol , Derivados da Hipromelose , Derivados da Hipromelose/química , Glicerol/química , Géis/química , Dessecação/métodos , Temperatura Alta , Lipídeos/química , Polímeros/químicaRESUMO
The multifunctionality of advanced laundry detergents primarily relies on the inclusion of functional solid particles, such as pearlescent powder, enzymes, and perfume microcapsules. However, the high-content surfactants in these detergents can render most existing suspending rheology modifiers ineffective, making it challenging to achieve uniform suspension of these functional particles. This compromises the overall functionality of laundry products. To address this, we have developed a binary rheology modifier comprising cellulose microgel and HPMC (hydroxypropyl methylcellulose), acting as the "island" and "chain," respectively. Together, they form an interconnected dynamic network that effectively "encapsulates" the functional particles. Furthermore, the cellulose microgel/HPMC rheology modifier demonstrates versatility, proving effective with various surfactants. Despite its potential, the suspension mechanism of cellulose microgel/HPMC remains elusive. Therefore, we conducted a comprehensive investigation, fabricating cellulose microgels with varying nanofabrication degrees and surface charges through TEMPO oxidation. Our findings highlight the critical role of the surficial structure of T-Microgel, specifically its nanofabrication degree, in influencing the dynamic network's fabrication, thereby impacting yield and thixotropic properties. The surface charge of T-microgel does not significantly influence the process. This research not only elucidates the intricate dynamics of cellulose microgel/HPMC interaction but also provides fundamental insights essential for the development of innovative rheology modifiers tailored for high-content surfactant applications.
Assuntos
Celulose , Microgéis , Reologia , Celulose/química , Microgéis/química , Tensoativos/química , Derivados da Hipromelose/química , Óxidos N-Cíclicos/químicaRESUMO
Collagen (COL)-hydroxypropyl methylcellulose (HPMC) blended films with apple polyphenol (AP) as cross-linking agent and antioxidant compound were developed to produce biodegradable active packaging film. The effects of AP content on the rheological behavior of the blended solution, the structure, physicochemical and functional properties of the blended film were systematically investigated. The incorporation of AP increased the viscosity and reduced the fluidity of COL-HPMC solution. The results of rheological tests and FTIR analysis manifested the formation of hydrogen bonding interactions between collagen, HPMC and AP, which made the structures of COL-HP-AP films more compact. The mechanical strength, UV-blocking ability, water-resistance performance and thermostability were gradually enhanced as increasing AP content. DPPH free radical scavenging experiment showed that a small amount of AP could efficiently improve the antioxidant activity of COL-HP film, and with increasing AP content to 5 wt%, the scavenging rate was as high as 94.23 %. Active film containing 5 wt% AP showed obvious antibacterial effect on E. coli and S. aureus, and it could effectively prevent the oxidation of vitamin C and reduce the accumulation of MDA on green pepper during the storage. COL-HP-AP films have great potential in food packaging field for extending the shelf life of food.