RESUMO
Phytochemicals as therapeutic alternatives can have a fundamental impact on the various stages of inflammation and its resolution. Prunetin is a naturally occurring isoflavone and has been claimed to have numerous therapeutic potentials. The objective of this study is preparation, characterization, and toxicity evaluation of microemulsion formulation containing prunetin (PMF) for potential oral applications. With this research, it was targeted to emphasize the way of improving the therapeutic efficacy of natural biomolecules with a nontoxic and effective formulation. In the study, the pseudo-ternary phase diagram was developed and PMF was characterized by conductivity, droplet size, viscosity and pH. Effects against to cytokines (IL-1ß and IL-6) and TNF-α levels of the PMF were determined by ELISA technique. Genotoxicity and acute oral toxicity tests were carried out according to OECD guidelines. The results showed that PMF is a colloid system that reduced proinflammatory cytokine levels in LPS-induced macrophage cells compared to the control group. PMF demonstrated no mutagenic activity against TA98, TA100, TA1535, and TA1537 Salmonella strains. The in vivo oral acute toxicity test results indicated that PMF did not show mortality or significant side effects even at 2000 mg/kg bw. This study represents PMF showed a good safety profile in animal study. It is thought that this formulation may have anti-inflammatory potential with further in vivo testing.
Assuntos
Anti-Inflamatórios , Isoflavonas , Animais , Anti-Inflamatórios/farmacologia , Isoflavonas/farmacologia , Citocinas , MutagênicosRESUMO
Modern drug carrier technologies, such as microemulsions with small droplet sizes and high surface areas, improve the ability of low water solubility active ingredients to permeate and localize. The goal of this study was to create microemulsion formulations for wound healing that contained both fusidic acid (FA), an antibacterial agent, and benzocaine (BNZ), a local anesthetic. Studies on characterization were carried out, including viscosity, droplet size, and zeta potential. The drug-loaded microemulsion had a stable structure with -3.014 ± 1.265 mV of zeta potential and 19.388 ± 0.480 nm of droplet size. In both in vitro release and ex vivo permeability studies, the microemulsion was compared with Fucidin cream and oily BNZ solution. According to the drug release studies, BNZ release from the microemulsion and the BNZ solution showed a similar profile (p > 0.05), while FA release from the microemulsion had a higher drug release compared to Fucidin cream (p < 0.001). The microemulsion presented lower drug permeation (p > 0.05) for both active ingredients, on the other hand, provided higher drug accumulation compared to the control preparations. Moreover, according to the results of in vitro wound healing activity, the microemulsion indicated a dose-dependent wound healing potential with the highest wound healing activity at the highest concentrations. To the best of our knowledge, this developed BNZ- and FA-loaded microemulsion would be a promising candidate to create new opportunities for wound healing thanks to present the active ingredients, which have low water solubility, in a single formulation and achieved higher accumulation than control preparations.
Assuntos
Benzocaína , Ácido Fusídico , Ácido Fusídico/farmacologia , Anestésicos Locais , Cicatrização , ÁguaRESUMO
CONTEXT: Eplerenone is a member of antihypertensives used individually or in combination with other medicines. Eplerenone exhibits poor solubility and is considered a class II drug. OBJECTIVE: Increasing the solubility of eplerenone by using both liquid and solid self-emulsifying drug delivery systems as an alternative to its marketed tablet product. METHODS: Solubility studies of eplerenone were done with different oils, surfactants, and co-surfactants to determine which one has the highest solubility for eplerenone and determine the preference in the formulations of liquid self-emulsifying drug delivery system. The solidification process was carried out with the adsorption to solid carrier method. Optimal ratios of components were specified with the pseudo-ternary phase diagram technique. Self-emulsifying drug delivery system formulations were characterized in terms of chemical interaction, droplet size/distribution, crystallization behaviors, and rheological evaluation. In vitro drug release studies were conducted and compared to pure drugs and marketed products. RESULTS: The solubility screening results showed high solubility of EPL in triacetin (11.99 mg/mL) as oil, Kolliphor®EL (≈ 2.65 mg/mL), and Tween80 (≈ 1.91 mg/mL) as surfactant and polyethylene glycol 200 (PEG200) (≈ 8.50 mg/mL), dimethyl sulfoxide (≈ 7.57 mg/mL), TranscutolP (≈ 6.03 mg/mL) as co-surfactant, respectively. Rheology studies revealed that liquid self-emulsifying drug delivery formulations exhibited non-Newtonian pseudoplastic flow. CONCLUSION: Solid self-emulsifying drug delivery systems prepared with Aerosil and Neusilin have shown tremendous improvement in terms of eplerenone dissolution by releasing the entire dose with boosted effect within 5 and 30 min respectively compared to the marketed product and pure eplerenone (p < 0.05).
Assuntos
Sistemas de Liberação de Medicamentos , Tensoativos , Solubilidade , Eplerenona , Emulsões/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Tensoativos/química , Disponibilidade BiológicaRESUMO
This research aimed to develop patches for transdermal delivery of acemetacin, which can be used to treat rheumatic diseasesand to determine their potential use. Patches were successfully created by solvent casting method using hydroxypropyl methylcellulose, propylene glycol, polyethylene glycol 400, tween 80, and dimethyl sulfoxide. Prepared patches were found using the Design of Experiments (DoE) method within the Quality by Design (QbD) approach. F1-ACM with a thickness of 0.1 ± 0.0 cm, a weight of 43.33 ± 6.29 mg, pH of 4.99 ± 0.24, moisture content of 18.33 ± 2.98%, a tensile strength of 9.196 ± 0.441 Mpa, elongation at break of 28.722 ± 0.803% and drug content of 100% was chosen as ideal formulation. 89.7% of ACM from F1-ACM was released in 5 min. F1-ACM significantly (p < 0.05) increased the response latency to the thermal stimulus at 90th (3.071 ± 0.517) and 120th (3.87 ± 0.332) min in the hot plate test. In the tail-flick experiment, F1-ACM significantly (p < 0.05) increased the reaction delay against heat stimuli at 90th (3.016 ± 0.695), 120th (2.884 ± 0.851), and 180th (2.893 ± 0.932) min. F1-ACM patch significantly (p < 0.001) inhibited paw edema formation at 1, 2, 3, 4, and 5 h after induction of inflammation as compared to the control group. Therefore, this formulation can be employed more efficiently for rheumatic disease.
Assuntos
Doenças Reumáticas , Pele , Humanos , Adesivo Transdérmico , Administração CutâneaRESUMO
In this study, hydrogels containing azelaic acid were developed using chitosan or HPMC (1-7%) for local treatment of acne vulgaris. Physicochemical properties such as viscosity, pH and mechanical properties were evaluated. In vitro release and ex vivo permeability studies were performed using the Franz diffusion cell system. The pH of the hydrogels was highly compatible with the skin pH and varied between 4.38 and 5.84. The cumulative release percentages of the hydrogels at the end of 6 hours were 65-78%, whereas the marketed product yielded 50% drug release. According to the ex vivo permeability results, azelaic acid accumulated in the skin was found to be 9.38 ± 0.65% (marketed cream), 19.53 ± 1.06% (K3), 10.96 ± 1.91% (H6). The antiacne studies with Cutibacterium acnes revealed that K3 (29.45 ± 0.95) and H6 (32.35 ± 0.15) had higher inhibition zones compared to the marketed cream (24.50 ± 0.90). Additionally, the gels were found to be highly stable as a result of the stability studies for 6 months. Among the hydrogels that were prepared based on experimental findings, K3 (3% Chitosan) and H6 (6% HPMC) represented elevated in vitro release profile, higher permeability and increased antiacne activity. The findings of this research suggest that the developed hydrogels might be an alternative to the marketed product.
Assuntos
Acne Vulgar , Quitosana , Acne Vulgar/tratamento farmacológico , Ácidos Dicarboxílicos/química , Humanos , HidrogéisRESUMO
In recent years, the hydrophobic active substances have led researchers to develop new formulations to enhance bioavailability and dissolution rate; brinzolamide, a lipophilic drug belongs to carbonic anhydrase inhibitors, which cause reduction of intraocular pressure in patients suffering from glaucoma. Currently, the marketed product of brinzolamide is in the form of ocular drops; nonetheless, the conventional drops provide decreased therapeutic efficacy owing to their low bioavailability and pulsed drug release. Thus, the development of novel ocular formulations such as topical microemulsions is of high importance. In this work, the preparation of new microemulsions containing brinzolamide (0.2, 0.5 and 1% w/w) and comprised from isopropyl myristate, tween 80 and span 20 and Cremophor EL was performed. The obtained microemulsions were further characterized for their physicochemical properties. In addition, Fourier Transformed-Infrared spectroscopy was used touate the compatibility of active ingredients and components. In vitro release studies along with kinetic modeling were performed using the dialysis membrane method in simulated tear fluid. Bioadhesion studies were performed using Texture analysis. Finally, in vitro ocular irritation based on EpiOcular™ Eye Irritation Test and cytocompatibility studies was performed to examine any possible harm on ocular cells and predict in vivo safety profile.
Assuntos
Olho/efeitos dos fármacos , Soluções Oftálmicas/administração & dosagem , Sulfonamidas/administração & dosagem , Tiazinas/administração & dosagem , Animais , Cromatografia Líquida de Alta Pressão , Emulsões/administração & dosagem , Emulsões/efeitos adversos , Emulsões/química , Fibroblastos/efeitos dos fármacos , Camundongos , Miristatos , Soluções Oftálmicas/efeitos adversos , Soluções Oftálmicas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Sulfonamidas/efeitos adversos , Sulfonamidas/química , Tiazinas/efeitos adversos , Tiazinas/químicaRESUMO
This study aimed to present an effective formulation targeting oral ulcers that will remain in the application site for a longer period, reducing the frequency of administration. As a candidate formulation, usnic acid (UA) was loaded into the optimum nanogels. The characterization studies included physical, rheological, and bioadhesive properties as well as in vitro release and ex vivo studies. The rheological results revealed that the nanogels present pseudoplastic flow behavior. In vitro drug release showed a prolonged pattern. In further, the chosen UA nanogels showed very low percentages of penetration and permeation. F13, which showed the highest release, suitable bioadhesive properties (0.475 ± 0.033 N/cm2) and eligible particle size (250.22 ± 4.11 nm), PDI (0.089 ± 0.052), and zeta potential (20.56 ± 0.330 mV) values were chosen for in vivo experiments. The selected UA nanogels showed effective antimicrobial activity against Bacillus Cereus and great in vivo wound healing properties. The results indicated that suitable UA nanogels with desired properties could be prepared. The therapeutic potential of the nanogels for oral ulcers was assessed using an animal model and the histopathological findings suggested that the optimized formulation is a good choice for oral ulcer treatment. Nonetheless, further research is recommended to support its efficacy by applying pharmacodynamic and pharmacokinetic studies in human individuals.
Assuntos
Benzofuranos/administração & dosagem , Nanogéis , Úlceras Orais/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Adesividade , Animais , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/farmacologia , Bacillus cereus/efeitos dos fármacos , Benzofuranos/farmacologia , Preparações de Ação Retardada , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Masculino , Úlceras Orais/patologia , Tamanho da Partícula , Coelhos , ReologiaRESUMO
The goal of this study was to develop and examine the nanogel-based topical delivery system of mupirocin. Nanogels were prepared with chitosan and bovine serum albumin by ionic gelation and Carbopol 940 was added to improve the gelling/adhesive properties. Detailed characterization studies were performed and the cellular binding capacity of radiolabeled nanogels was investigated on CCD-1070Sk cell lines. Results indicate the successful formation of nanogels with particle size and zeta potential ranged between 341.920-603.320 nm and 13.120-24.300 mV, respectively. The mechanical and rheological studies proved pseudoplastic and strong elastic gel behavior (G' > G''). Mupirocin was successfully entrapped into nanogels with a ratio of more than 95% and the loaded drug was slowly released up to 93.89 ± 3.07% within 24 h. The ex vivo penetration and permeation percentages of mupirocin were very low (1.172 ± 0.202% and 0.161 ± 0.136%) indicating the suitability of nanogels for dermal use against superficial skin infections. The microbiological studies pointed out the effectiveness of nanogels against Staphylococcus aureus strains. Nanogels did not show toxicity signs and the cell binding capacity of radiolabeled formulations was found to be higher than [99mTc]NaTcO4 to CCD-1070Sk cell line. Overall, mupirocin nanogels might be considered as a potential and safe topical treatment option for bacterial skin infections.
Assuntos
Antibacterianos/administração & dosagem , Mupirocina/administração & dosagem , Nanogéis , Resinas Acrílicas/administração & dosagem , Resinas Acrílicas/química , Administração Cutânea , Antibacterianos/farmacocinética , Quitosana/administração & dosagem , Quitosana/química , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Humanos , Mupirocina/farmacocinética , Nanogéis/administração & dosagem , Nanogéis/química , Permeabilidade , Compostos Radiofarmacêuticos , Soroalbumina Bovina/administração & dosagem , Soroalbumina Bovina/química , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacosRESUMO
The air-dried aerial parts of Phlomis russeliana (Sims) Lag. Ex Benth. was extracted by methanol and fractionated by n-hexane, dichloromethane, and ethyl acetate, respectively. The wound healing properties of P. russeliana extract gel was evaluated using the in vivo excisional wound model using Balb-c mice. Initially, the P. russeliana methanol extract showed LOX inhibitory activity at IC50 = 23.2 µg/mL, whereas the DPPH⢠assay showed IC50 = 0.89 mg/mL, and the ABTS⢠assay showed IC50 = 0.99 mg/mL, respectively. In addition, a remarkable anti-inflammatory activity was observed in the cell culture assay. Thereafter, activity-guided fractionation was performed by LOX enzyme inhibition assays, and the structures of the two most active fractions were revealed by both GC-FID and GC/MS analyses, simultaneously. Phytol and 1-heptadecanoic acid were characterized as the active constituents. Moreover, the P. russeliana extract gel formulation was applied for in vivo tests, where the new gel formulation supported the in vitro anti-inflammatory activity findings. As a conclusion, this experimental results support the wound healing evidence based on the ethnobotanical application of Phlomis species with further potential.
Assuntos
Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Phlomis/química , Fitoterapia , Extratos Vegetais/farmacologia , Dermatopatias/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Bactérias/efeitos dos fármacos , Composição de Medicamentos , Géis , Inflamação/etiologia , Inflamação/patologia , Camundongos , Camundongos Endogâmicos BALB C , Dermatopatias/etiologia , Dermatopatias/patologiaRESUMO
Psoriasis is a chronic autoinflammatory disorder characterized by patches of abnormal skin. For psoriasis management, the application of topical retinoids as Tazarotene is recommended. However, Tazarotene could induce skin irritation limiting its use. Herein, it is evaluated the possible usage of in situ gels for tazarotene skin delivery. The topical in situ gels were developed using thermosensitive poloxamers via cold method. They were examined for their appearance, sol-gel temperature, clarity, pH, viscosity, in vitro release, and stability. Their biocompatibility was evaluated by investigating their cytotoxicity and irritation inducing capacity. The possible anti-inflammatory and analgesic activities were determined by measuring the nitric oxide and prostaglandin E2 levels production in LPS-stimulated RAW264.7 murine macrophage cells. It was revealed that the in situ gels had no cytotoxic effect (â¼95-100% cell viability) and nor irritation potential (â¼97% cell viability), according to the in vitro EpiDerm™ reconstituted skin irritation test. Additionally, the 10% tazarotene-in situ gels showed possible analgesic activity since the production of prostaglandin E2 (PGE2) was decreased. In further, both concentrations of 5% and 10% tazarotene-in situ gels inhibited significantly the nitrite oxide production at 16% and 19%, respectively. Finally, the prepared in situ gels can act as a potential non-irritant alternative option for tazarotene topical skin delivery.
Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Géis/farmacologia , Ácidos Nicotínicos/farmacologia , Psoríase/tratamento farmacológico , Animais , Materiais Biocompatíveis , Linhagem Celular , Fármacos Dermatológicos/farmacologia , Humanos , Camundongos , Células RAW 264.7 , Retinoides/farmacologia , Pele/efeitos dos fármacosRESUMO
The objective of the present research was to examine the possible usage of terbinafine loaded hydrogels for vaginal application as part of vaginal candidiasis treatment. Vaginal candidiasis belongs to the most frequent gynecological disorders. Various antifungal drugs are used for its treatment, with Terbinafine being one of them. In this study, new gel formulations were prepared for Terbinafine vaginal delivery. Natural polymers such as chitosan, sodium carboxymethylcellulose, and Carbopol were used for the development of Terbinafine vaginal gels. The developed gels were examined for their viscosity and spreadability, pH and mechanical properties. The most optimal formulations were further evaluated for their in vitro release behavior and antifungal activities. In further, the cytotoxicity and irritation inducing capacity of optimum gel formulations were evaluated. In vitro drug release studies demonstrated that terbinafine release was prolonged whereas anti-candida activity in several species showed the superiority of the gels compared to the marketed product. G-5 and G-8 gels did not cause lysis, hemorrhage and coagulation, therefore, classified as non-irritant. The optimal formulations were also studied for their stability, demonstrating that they were stable for 3 months.
Assuntos
Antifúngicos/administração & dosagem , Candidíase Vulvovaginal/tratamento farmacológico , Portadores de Fármacos/química , Terbinafina/administração & dosagem , Administração Intravaginal , Animais , Antifúngicos/farmacologia , Antifúngicos/toxicidade , Candidíase Vulvovaginal/microbiologia , Galinhas , Membrana Corioalantoide/efeitos dos fármacos , Liberação Controlada de Fármacos , Feminino , Hidrogéis , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Polímeros/química , Terbinafina/farmacologia , Terbinafina/toxicidade , Testes de Toxicidade , Cremes, Espumas e Géis Vaginais , ViscosidadeRESUMO
The objective of the present research was to examine the possible usage of microemulsion based gel for fusidic acid (FA) dermal application as burn wound treatment. During the preparation of microemulsion, ethyl oleate as oil phase, tween 80 as a surfactant, ethanol as co-surfactant, water as aqueous phase were used. The prepared microemulsions were evaluated for clarity, pH, viscosity and FA content. Moreover, stability, sterility, antibacterial activity, in vitro release of the formulations were also evaluated. The results showed that the FA loaded microemulsion and microemulsion based gel formation and characteristics were related to many parameters of the components. The performed optimized microemulsion-based gel showed good stability over a period of 3 months. The antibacterial activity of microemulsion-based gel was found to be comparable with marketed cream. RAW 264.7 macrophages were used to determine cell viability (MTT assay) and nitric oxide production. MBG and FA-MBG significantly inhibit the production of the inflammatory mediator NO in LPS-stimulated RAW 264.7 cells in a concentration-dependent manner. The wound healing property was evaluated by histopathological examination and by measuring the wound contraction. The % of wound area in rats treated with FA (2%) loaded microemulsion based gel ranged from 69.30% to 41.39% in the period from 3 to 10 days. In conclusion, FA loaded microemulsion based gel could be offered as encouraging strategy as dermal systems for the burn wound treatment.
RESUMO
In this study, novel adhesive films were prepared for Mupirocin dermal delivery. Natural polymers as chitosan, sodium alginate and carbopol were used for films development to evaluate possible interactions and drug release properties. Solvent evaporation method was used for films preparation. Preliminary studies involved FT-IR spectroscopy and Scanning Electron Microscopy to specify interactions and morphology. Thickness, tensile strength and water uptake in phosphate buffer saline were evaluated whereas in vitro release studies were also performed. In vitro drug release studies demonstrated that mupirocin release was improved. Ex vivo bioadhesion and permeation studies using Balb-c mice were performed to check the suitability of the films. Antimicrobial ability was evaluated by agar well diffusion tests. Finally, excisional wound model applied to test the wound healing effect and evaluated macroscopic and histopathologically. One formulation was found more effective compared to the market product for wound healing at Balb-c mice.
RESUMO
The purpose of the current research was to prepare and evaluate the potential use of microemulsion-based hydrogel (MBH) formulations for dermal delivery of benzocaine (BZN). The pseudoternary-phase diagrams were constructed for various microemulsions composed of isopropyl myristate (IPM) as oil phase, Span 20, Tween 20, Tween 80, cremophor EL and cremophor RH40 as surfactants, ethanol as cosurfactant and distilled water as aqueous phase. Finally, concentration of BZN in microemulsions was 2% (w/w). The physicochemical properties, such as conductivity, viscosity, pH, droplet size, polydispersity index and zeta potential of microemulsions, were measured. Carbopol 940 was used to convert BZN-loaded microemulsions into gel form without affecting their structure. Furthermore, excised rat abdominal skin was used to compare permeation and penetration properties of BZN loaded M3 and M3BHs with BZN solution. According to ex vivo study results, BZN-loaded M3BH1 showed highest flux values and high release rate values, and furthermore, this gel formulation had low surfactant content. Finally, in order to learn the localization of formulations within the dermal penetration, formulations and BZN solution were labeled with red oil O and subjected to fluorescence observation. In conclusion, BZN-loaded MBHs could be offered as a promising strategy for dermal drug delivery.
Assuntos
Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacocinética , Benzocaína/administração & dosagem , Benzocaína/farmacocinética , Emulsões/química , Hidrogéis/química , Absorção Cutânea , Resinas Acrílicas/química , Administração Cutânea , Animais , Portadores de Fármacos/química , Masculino , Miristatos/química , Polietilenoglicóis/química , Polissorbatos/química , Ratos WistarRESUMO
Nebivolol (NB)-loaded solid lipid nanoparticles (SLNs) were prepared and modified with chitosan oligosaccharide lactate (COL) and polyethylene glycol (PEG) stearate for improvement of its oral bioavailability. Compritol, poloxamer and lecithin were used for the preparation of SLNs by homogenisation method. After in vitro characterisation effect of lipase, pepsin, or pancreatin on degradation and release rate were investigated. Cytotoxicity and permeation were studied on Caco-2 cells. As COL concentration increased in SLNs, size and zeta potential increased. PEG concentration was reversely proportional to particle size with no change in zeta potential. Encapsulation efficiencies (EEs) were determined as 84-98%. DSC confirmed solubilisation of NB in lipid matrix. A sustained release with no burst effect was determined. The presence of enzymes affected the release. SLNs did not reveal cytotoxicity and highest permeability was obtained with PEG modification. PEG-modified SLNs could be offered as a promising strategy for oral delivery of NB.
Assuntos
Quitosana , Hipertensão/tratamento farmacológico , Nanopartículas/química , Nebivolol , Oligossacarídeos , Polietilenoglicóis , Administração Oral , Células CACO-2 , Quitosana/química , Quitosana/farmacocinética , Quitosana/farmacologia , Humanos , Nebivolol/química , Nebivolol/farmacocinética , Nebivolol/farmacologia , Oligossacarídeos/química , Oligossacarídeos/farmacocinética , Oligossacarídeos/farmacologia , Polietilenoglicóis/química , Polietilenoglicóis/farmacocinética , Polietilenoglicóis/farmacologiaRESUMO
Nanocarriers, due to their unique features, are of increased interest among researchers working with pharmaceutical formulations. Polymeric nanoparticles and nanocapsules, involving non-toxic biodegradable polymers, liposomes, solid lipid nanoparticles, and inorganic-organic nanomaterials, are among the most used carriers for drugs for a broad spectrum of targeted diseases. In fact, oral, injectable, transdermal-dermal and ocular formulations mainly consist of the aforementioned nanomaterials demonstrating promising characteristics such as long circulation, specific targeting, high drug loading capacity, enhanced intracellular penetration, and so on. Over the last decade, huge advances in the development of novel, safer and less toxic nanocarriers with amended properties have been made. In addition, multifunctional nanocarriers combining chemical substances, vitamins and peptides via coupling chemistry, inorganic particles coated by biocompatible materials seem to play a key role considering that functionalization can enhance characteristics such as biocompatibility, targetability, environmental friendliness, and intracellular penetration while also have limited side effects. This review aims to summarize the "state of the art" of drug delivery carriers in nanosize, paying attention to their surface functionalization with ligands and other small or polymeric compounds so as to upgrade active and passive targeting, different release patterns as well as cell targeting and stimuli responsibility. Lastly, future aspects and potential uses of nanoparticulated drug systems are outlined.
Assuntos
Dendrímeros/química , Nanopartículas Metálicas/química , Nanodiamantes/química , Nanotubos de Carbono/química , Animais , HumanosRESUMO
In this work, a comparison between two different preparation methods for the improvement of dissolution rate of an antifungal agent is presented. Poly(ε-caprolactone) (PCL) electrospun fibers and ß-cyclodextrin (ß-CD) complexes, which were produced via an electrospinning process and an inclusion complexation method, respectively, were addressed for the treatment of fungal infections. Voriconazole (VRCZ) drug was selected as a model drug. PCL nanofibers were characterized on the basis of morphology while phase solubility studies for ß-CDs complexes were performed. Various concentrations (5, 10, 15 and 20 wt %) of VRCZ were loaded to PCL fibers and ß-CD inclusions to study the in vitro release profile as well as in vitro antifungal activity. The results clearly indicated that all formulations showed an improved VRCZ solubility and can inhibit fungi proliferation.
Assuntos
Antifúngicos/administração & dosagem , Portadores de Fármacos/química , Nanofibras/química , Voriconazol/administração & dosagem , beta-Ciclodextrinas/química , Administração Oral , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Liberação Controlada de Fármacos , Poliésteres/química , Voriconazol/farmacologiaRESUMO
Naproxen (Np) is an example of a non-steroidal anti-inflammatory drug (NSAID) commonly used for the reduction of pain and inflammation. In order to develop an alternative formulation for the topical administration of Np, microemulsions were evaluated as delivery vehicles. Four formulations were prepared using isopropyl myristate (IPM) as oil phase, Span 80, Labrafil M, Labrasol, Cremophor EL as surfactants, ethanol as co-surfactant and distilled water or 0.5 N NaOH solution as aqueous phase. The final concentration of Np in the microemulsion system was 100 mg/g (w/w). The physicochemical properties such as electrical conductivity, droplet size, viscosity, pH and phase inversion temperature of microemulsions were measured. Stability tests of the formulations were also performed at 5±2, 25±2 and 40±2°C. The abilities of various microemulsions and selected commercial (C) formulation to deliver Np through the skin were evaluated in vitro using diffusion cells fitted with rat skins. The in vitro permeation data showed that microemulsions increased the permeation rate of Np between 4.335-9.040 times over the C formulation. Furthermore Np successfully permeated across the skin from the microemulsion with the highest flux rate (1.347±0.005 mg·cm(-2)·h(-1)) from a formulation (M4Np) consisting of IPM (2.36 g), Labrosol (0.13 g), Span 80 (0.62 g), ethanol (5.23 g), 0.5 N NaOH solution (0.66 g) and Np (1 g). According to the histological investigations, no obvious skin irritation was observed for the studied microemulsions. These results indicate that the microemulsion formulation may be appropriate vehicles for the topical delivery of Np.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Emulsões/química , Naproxeno/administração & dosagem , Veículos Farmacêuticos/química , Absorção Cutânea , Pele/metabolismo , Administração Cutânea , Animais , Anti-Inflamatórios não Esteroides/farmacocinética , Emulsões/metabolismo , Masculino , Miristatos/química , Miristatos/metabolismo , Naproxeno/farmacocinética , Veículos Farmacêuticos/metabolismo , Ratos , Ratos Wistar , Pele/ultraestrutura , Tensoativos/química , Tensoativos/metabolismoRESUMO
BACKGROUND: The domperidone maleate, a lipophilic agent classified as a Biopharmaceutical Classification System Class II substance with weak water solubility. Self- Emulsifying Drug Delivery System is a novel approach to improve water solubility and, ultimately bioavailability of drugs. OBJECTIVE: This study aimed to develop and characterize new domperidone-loaded self-emulsifying drug delivery systems as an alternative formulation and to evaluate the permeability of domperidone-loaded self-emulsifying drug delivery systems by using Caco-2 cells and via single-pass intestinal perfusion method. METHOD: Three self-emulsifying drug delivery systems were prepared and characterized in terms of pH, viscosity, droplet size, zeta potential, polydispersity index, conductivity, etc. Each formulation underwent 10, 100, 200, and 500 times dilution in intestinal buffer pH 6.8 and stomach buffer pH 1.2, respectively. Female Sprague Dawley rats were employed for in situ single-pass intestinal perfusion investigations. RESULTS: Results of the study revealed that the ideal self-emulsifying drug delivery systems formulation showed narrow droplet size, ideal zeta potential, and no conductivity. Additionally, as compared to the control groups, the optimum formulation had better apparent permeability (12.74 ± 0.02×10-4) from Caco-2 cell monolayer permeability experiments. The study also revealed greater Peff values (2.122 ± 0.892×10-4 cm/s) for the optimal formulation from in situ intestinal perfusion analyses in comparison to control groups (Domperidone; 0.802±0.418×10-4 cm/s). CONCLUSION: To conclude, prepared formulations can be a promising way of oral administration of Biopharmaceutical Classification System Class II drugs.
RESUMO
The delivery of active molecules via the skin seems to be an efficient technology, given the various disadvantages of oral drug administration. Skin, which is the largest human organ of the body, has the important role of acting as a barrier for pathogens and other molecules including drugs; in fact, it serves as a primary defense system blocking any particle from entering the body. Therefore, to overcome the skin barriers and poor skin permeability, researchers implement novel carriers which can effectively carry out transdermal delivery of the molecules. Another significant issue which medical society tries to solve is the effective dermal delivery of molecules especially for topical wound delivery. The application of nanogels is only one of the available approaches offering promising results for both dermal and transdermal administration routes. Nanogels are polymer-based networks in nanoscale dimensions which have been explored as potent carriers of poorly soluble drugs, genes and vaccines. The nanogels present unique physicochemical properties, i.e., high surface area, biocompatibility, etc., and, importantly, can improve solubility. In this review, authors aimed to summarize the available applications of nanogels as possible vehicles for dermal and transdermal delivery of active pharmaceutical ingredients and discuss their future in the pharmaceutical manufacturing field.