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Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/metabolismo , Liberación de Fármacos/fisiología , Pectinas/administración & dosificación , Pectinas/metabolismo , Animales , Sistemas de Liberación de Medicamentos/métodos , Sistemas de Liberación de Medicamentos/tendencias , Humanos , Hidrogeles/administración & dosificación , Hidrogeles/metabolismoRESUMEN
Pre-clinical development comprises of different procedures that relate drug discovery in the laboratory for commencement of human clinical trials. Pre-clinical studies can be designed to recognize a lead candidate from a list to develop the procedure for scale-up, to choose the unsurpassed formulation, to determine the frequency, and duration of exposure; and eventually make the foundation of the anticipated clinical trial design. The foremost aim in the pharmaceutical research and industry is the claim of drug product quality throughout a drug's life cycle. The particulars of the pre-clinical development process for different candidates may vary; however, all have some common features. Typically in vitro, in vivo or ex vivo studies are elements of pre-clinical studies. Human pharmacokinetic in vivo studies are often supposed to serve as the 'gold standard' to assess product performance. On the other hand, when this general assumption is revisited, it appears that in vitro studies are occasionally better than in vivo studies in assessing dosage forms. The present review is compendious of different such models or approaches that can be used for designing and evaluation of formulations for nail delivery with special reference to anti-fungal agents.
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Antifúngicos/administración & dosificación , Vías de Administración de Medicamentos , Uñas , Animales , Hongos/efectos de los fármacos , Humanos , Pruebas de Sensibilidad MicrobianaRESUMEN
INTRODUCTION: Hydatid cyst of the breast is very rare. It is challenging to differentiate it from other tumoral lesions of the breast. Only few reports of breast hydatid cyst are published and majority of the reported cases have been diagnosed postoperatively as it is not possible to reach definitive diagnosis with clinical examination and radiological investigations only. PRESENTATION OF CASE: A 31-year old woman presented with a painless lump in the right breast since one year duration. On clinical examination, a non-mobile, firm lump was detected in the right breast associated with nipple retraction, but there was no axillary lymphadenopathy. This case was diagnosed as hydatid cyst incidentally during surgery from its gross appearance which mimics that of a liver hydatid cyst, normally common in this endemic area. DISCUSSION: Hydatid disease is a parasitic infection caused by the larval form of Echinococcus granulosus and seen endemically among sheep-raising communities. The breast can be a primary site or part of a disseminated hydatidosis. It might mimic fibroadenoma, phyllodes tumors, chronic abscesses, or even carcinoma. Preoperative diagnosis can be made by fine needle aspiration cytology. It also can be diagnosed by radiological or serologic means but neither of them is definitive. Surgery is the treatment of choice. CONCLUSION: Hydatid cyst of the breast is very uncommon but it should be included in differential diagnosis of breast lumps for patients living in endemic areas.
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Tablet coating is the most useful method to improve tablet texture, odour and mask taste. Thus, the present investigation was aimed at developing an industrially acceptable aqueous tablet coating material. The physico-chemical, electrical and SEM investigations ensures that blending of Tamarindus indica (Linn.) pectin (TP) with chitosan gives water resistant film texture. Therefore, CH-TP (60:40) spray coated tablets were prepared. The evaluation of CH-TP coated tablets showed enhanced adhesive force strength (between tablet surface to coat) and negligible cohesive force strength (between two tablets) both evaluated using texture analyzer. The comparison of CH-TP coated tablets with Eudragit coated tablets further supported superiority of the former material. Thus, the findings pointed towards the potential of CH-TP for use as a tablet coating material in food as well as pharmaceutical industry.
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Ensayo de Materiales , Pectinas/química , Comprimidos , Tamarindus/química , Rastreo Diferencial de Calorimetría , Microscopía Electrónica de RastreoRESUMEN
We have optimized the synthesis of spray dried ethylenediaminediacetic acid bis(carbido amide chitosan) (ED-chitosan) microparticles employing 3(2) full factorial design. The ED-chitosan microparticles were characterized using FTIR-ATR, DSC analysis, oil adsorbing capacity, oil desorbing capacity, surface free energy and dynamic advancing contact angle. The ED-chitosan microparticles were found to have enhanced dispersive component of surface free energy as compared to Aerosil 200. However, they showed lower polar component. This was associated with similar oil adsorbing capacity but higher desorbing capacity. The SEM analysis supported ability of ED-chitosan microparticles to completely spread lipophillic drug over its surface. The reconstituted nanoemulsion generated from ED-chitosan was stable (neutral zeta potential), spherical shaped and 110 nm size (TEM analysis). Further, these nanoemulsions when prepared with primaquine were successfully enhanced in vitro dissolution and its ex vivo performance. Thus, the study showed new possibilities of industrial acceptance of ED-chitosan microparticles as a solid carrier for the fabrication of nanoemulsion.
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Quitosano/química , Portadores de Fármacos/química , Ácido Edético/química , Nanoestructuras/química , Animales , Portadores de Fármacos/administración & dosificación , Emulsiones , Técnicas In Vitro , Intestino Delgado/metabolismo , Nanoestructuras/administración & dosificación , Primaquina/administración & dosificación , Primaquina/química , Dióxido de Silicio/química , PorcinosRESUMEN
The present investigation was aimed at synthesis of chitosan-EDTA superior microparticles (COECH) bearing high oil adsorbing and oil desorbing properties. These superior particles were prepared by thermal amide conjugation of COO(-) group of EDTA with NH2 group of chitosan employing spray-drying technique. The synthesis was optimized using 4(2) full factorial design. The particles showed high oil adsorbing capacity as well as oil desorbing capacity with enhanced dispersive components of surface free energy as compared to Aerosil 200. In addition, these COECH microparticles showed higher amphotericin B loading capacity, enhancement in the in vitro dissolution performance (12-fold) and produces nanoemulsion in the size range of 70-90 nm. Further, the results were in consonance with those observed during ex vivo performance. Thus, the findings revealed simple synthesis of COECH microparticles that showed superior properties of solid substrate for the development of amphotericin B nanoemulsion.
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Anfotericina B/química , Antifúngicos/química , Antiprotozoarios/química , Quitosano/síntesis química , Portadores de Fármacos/química , Ácido Edético/análogos & derivados , Administración Oral , Anfotericina B/metabolismo , Animales , Antifúngicos/metabolismo , Antiprotozoarios/metabolismo , Rastreo Diferencial de Calorimetría , Quitosano/química , Desecación , Portadores de Fármacos/metabolismo , Composición de Medicamentos , Ácido Edético/síntesis química , Ácido Edético/química , Emulsiones , Técnicas In Vitro , Absorción Intestinal , Intestino Delgado/metabolismo , Microesferas , Sus scrofa , TermodinámicaRESUMEN
Pectin is used in a number of foods as a gelling agent, thickener, texturizer, emulsifier and stabilizer. Bael fruit, obtained from Aegle marmelos, is a rich source of pectin. Bael fruit pectin (BFP) was extracted from ripe Bael fruits. The process yielded 15% (w/w) pure BFP. The swelling index decreased in the following order: water>pH 7.4>pH 6.8>pH 1.2>HCl (0.1N). Galacturonic acid content of 87.8%, degree of esterification of 47.2%, 17.3% methoxy groups, 0.29% acetyl groups and equivalent weight of 1209.5, indicate it to be a good gelling agent and easily amenable to derivatization. BFP exhibited a significant concentration-dependent prolongation of prothrombin time. The absence of hemagglutinating activity and antinutritional factors coupled with the activity to confer better emulsion capacity, stability and antimicrobial activity gives BFP a clear edge over commercial citrus pectin (CP) for exploitation as an additive in food and pharmaceuticals.
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Aegle/química , Frutas/química , Pectinas/química , Reología/métodos , Animales , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Bacillus cereus/efectos de los fármacos , Fenómenos Químicos , Emulsionantes/química , Emulsionantes/aislamiento & purificación , Emulsiones/química , Eritrocitos/efectos de los fármacos , Esterificación , Alimentos , Geles/química , Pruebas de Hemaglutinación , Ácidos Hexurónicos/química , Ácido Clorhídrico/química , Concentración de Iones de Hidrógeno , Pectinas/aislamiento & purificación , Pectinas/farmacología , Conejos , Reproducibilidad de los Resultados , Propiedades de Superficie , Factores de Tiempo , Agua/químicaRESUMEN
Pectin of Aegle marmelos (AP) ripe fruits processed in equal proportion with chitosan (CH) formed films that exhibited minimum swelling index and volume index on exposure to buffers of acidic and alkaline pH. Highest contact angle and spreading coefficient coupled with lowest work of adhesion in all buffers for this film suggested availability of limited number of functional groups for interaction with water molecules due to optimum cross-linking between -NH(3)(+) groups of CH and -COO(-) groups of AP. This contention was substantiated by the presence of almost negligible charge on this film. The endothermic transition ΔH characteristic of -NH(3)(+)-COO(-) cross-linking between groups in this film was observed to decrease by only 1% after its sequential exposure to pH 1.2 (3 h) and pH 7.4 (6 h). Furthermore, the absence of pores or erosion in the scanning electron photomicrograph suggested the versatility of this film due to its resistance to acidic and alkaline pH.
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Aegle/química , Quitosano/química , Frutas/química , Membranas Artificiales , Pectinas/química , Concentración de Iones de HidrógenoRESUMEN
The present study was aimed to exploit the antibacterial/antifungal and film coating potential of Chitosan-EDTA (CH-EDTA) conjugate in combination with mesalamine (anti-inflammatory agent) for the early recovery from TNBS induced coilitis. The results suggested CH:EDTA (1:1) spray coated mesalamine tablets has an ability to transport drug in buffer pH 6.8 with rat caecal content condition. The CH-EDTA shows high level of adhesiveness of coat with core tablet. Further, FTIR, DSC and SEM analysis suggested spray coating of CH-EDTA on tablets was beneficial as compared to ladling method as it enhances interaction density and showed resistance from pH (1.2, 6.8 and 7.4). The pharmacokinetic parameters, AUC and AUMC of spray coated tablets were respectively, 4.70 fold and 2.10 fold increased. A synergistic therapeutic effect with CH-EDTA spray coated mesalamine was observed as evaluated by colon/body weight ratio, clinical activity score and damage score. X ray image study supported that CH-EDTA conjugate successfully delivered MSA tablets to large intestine. Histopathology of colon tissues showed rapid recovery from TNBS induced colitis in rats within 4 days. The findings revealed decreased recovery period was due to combined effect of both CH-EDTA and MSA to treat TNBS induced colitis.
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Quitosano/uso terapéutico , Colitis/tratamiento farmacológico , Ácido Edético/análogos & derivados , Mesalamina/uso terapéutico , Adhesividad/efectos de los fármacos , Animales , Rastreo Diferencial de Calorimetría , Quitosano/administración & dosificación , Quitosano/farmacocinética , Quitosano/farmacología , Colitis/inducido químicamente , Colon/efectos de los fármacos , Colon/patología , Sinergismo Farmacológico , Ácido Edético/administración & dosificación , Ácido Edético/farmacocinética , Ácido Edético/farmacología , Ácido Edético/uso terapéutico , Concentración de Iones de Hidrógeno , Mesalamina/administración & dosificación , Mesalamina/farmacocinética , Mesalamina/farmacología , Microscopía Electrónica de Rastreo , Polvos , Ratas , Ratas Sprague-Dawley , Espectroscopía Infrarroja por Transformada de Fourier , Comprimidos , Ácido TrinitrobencenosulfónicoRESUMEN
The present study was aimed to develop chitosan-EDTA films and evaluate their physico-chemical and mechanical properties. The physical properties suggested lowest swelling, volume and volume index of films prepared by employing equal weight of chitosan (CH) and EDTA (1.5% w/v). The CH:EDTA film (1:l, on weight basis) showed minimum contact angle, work of adhesion and high negative spreading coefficient indicating lipophilic behavior of film. Further, the FTIR and DSC analysis suggested maximum crosslinking density in film prepared with equal proportion of CH and EDTA. The mechanical properties explored using texture analyzer revealed increasing the proportions of EDTA rendered the films more flexible and decreased their hardness. Furthermore, in vitro permeation of 5-FU and mesalamine with different solubilities showed minimum permeation across CHEDTA (1:1) film, indicating high crosslinking density that decreased void space inside the film. Hence, the CHEDTA conjugate could be considered to be possess great potential for various pharmaceutical applications such as film based delivery systems, controlled and sustained delivery systems etc.
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Quitosano/química , Ácido Edético/química , Rastreo Diferencial de Calorimetría , Concentración de Iones de Hidrógeno , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Stevioside, a diterpene glycoside, is well known for its intense sweetness and is used as a non-caloric sweetener. Its potential widespread use requires an easy and effective extraction method. Enzymatic extraction of stevioside from Stevia rebaudiana leaves with cellulase, pectinase and hemicellulase, using various parameters, such as concentration of enzyme, incubation time and temperature, was optimised. Hemicellulase was observed to give the highest stevioside yield (369.23±0.11µg) in 1h in comparison to cellulase (359±0.30µg) and pectinases (333±0.55µg). Extraction from leaves under optimised conditions showed a remarkable increase in the yield (35 times) compared with a control experiment. The extraction conditions were further optimised using response surface methodology (RSM). A central composite design (CCD) was used for experimental design and analysis of the results to obtain optimal extraction conditions. Based on RSM analysis, temperature of 51-54°C, time of 36-45min and the cocktail of pectinase, cellulase and hemicellulase, set at 2% each, gave the best results. Under the optimised conditions, the experimental values were in close agreement with the prediction model and resulted in a three times yield enhancement of stevioside. The isolated stevioside was characterised through 1H-NMR spectroscopy, by comparison with a stevioside standard.
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The present study examines the acute, sub-acute toxicity, and cytotoxicity of paclitaxel elastic liposomal formulation in comparison to a marketed Cremophor EL (polyoxyethylated castor oil):ethanol (1:1, v/v) based formulation. In the previous study, Cremophor EL free paclitaxel elastic liposomal formulation was developed and characterized. Cytotoxicity of formulation was evaluated by MTT assay using A549 cell lines. Percentage intracellular uptake of paclitaxel elastic liposomal and marketed formulation was determined using a fluorescence activating cell sorting assay (FACS) and fluorescence microscopy techniques. Single and repeated dose toxicity measurement showed no mortality, hematological, biochemical, or histopathological changes up to a dose of 120 mg/kg for paclitaxel elastic liposomal formulation, in comparison the marketed formulation showed toxicity at a dose of 40 mg/kg. Maximum tolerated dose (MTD) for paclitaxel elastic liposomal and marketed formulation was found to be 160 mg/kg and 40 mg/kg, respectively. Results of FACS analysis showed a 94.6 ± 2.5% intracellular uptake of fluorescence marker acridine orange (AO) loaded in elastic liposomes; in comparison the AO solution showed only a 19.8 ± 1.1% uptake. Paclitaxel elastic liposomal formulation seems to be a better alternative for safe and effective delivery of paclitaxel. This study proves the safety and higher intracellular uptake of paclitaxel elastic liposomal formulation.
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Elasticidad , Glicerol/análogos & derivados , Líquido Intracelular/metabolismo , Paclitaxel/metabolismo , Animales , Línea Celular Tumoral , Química Farmacéutica , Evaluación Preclínica de Medicamentos/métodos , Femenino , Glicerol/efectos adversos , Glicerol/metabolismo , Humanos , Liposomas , Masculino , Ratones , Paclitaxel/efectos adversos , Vehículos Farmacéuticos/efectos adversos , Distribución Aleatoria , Pruebas de Toxicidad Aguda/métodosRESUMEN
In the present study an elastic liposomes-based paclitaxel formulation was developed with the objective to remove Cremophor EL. Cremophor EL is currently used for solubilizing paclitaxel in the marketed formulation and is known to produce toxic effects. Elastic liposomal paclitaxel formulation was extensively characterized in vitro, ex-vivo, and in vivo. The results obtained were compared against the marketed paclitaxel formulation. The maximum amount of paclitaxel loaded in the elastic liposomal formulation was found to be 6.0 mg/ml, which is similar to the commercial strength of marketed paclitaxel formulation. In vitro skin permeation and deposition studies showed 10.8-fold enhanced steady state transdermal flux and 15.0-fold enhanced drug deposition in comparison to drug solution. These results further confirmed with the vesicle-skin interaction study using FTIR technique. Results of the hemolytic toxicity assay indicate that elastic liposomal formulation induced only 11.2 ± 0.2% hemolysis in comparison to the commercial formulation which showed 38 ± 3.0%. Further, results of the Draize test showed no skin irritation of paclitaxel elastic liposomal formulation. Findings of the study demonstrate that elastic liposomes as a carrier is an attractive approach for localized delivery of paclitaxel.
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Antineoplásicos Fitogénicos/administración & dosificación , Paclitaxel/administración & dosificación , Absorción Cutánea , Animales , Antineoplásicos Fitogénicos/farmacocinética , Antineoplásicos Fitogénicos/toxicidad , Preparaciones de Acción Retardada , Elasticidad , Glicerol/análogos & derivados , Glicerol/química , Glicerol/toxicidad , Hemólisis/efectos de los fármacos , Liposomas , Masculino , Paclitaxel/farmacocinética , Paclitaxel/toxicidad , Conejos , Ratas , Espectroscopía Infrarroja por Transformada de Fourier , Pruebas de Toxicidad/métodosRESUMEN
PURPOSE: In the present study, Cremophor EL free paclitaxel elastic liposomal formulation consisting of soya phosphatidylcholine and biosurfactant sodium deoxycholate was developed and optimized. The toxicological profile, antitumor efficacy and hemolytic toxicity of paclitaxel elastic liposomal formulation in comparison to Cremophor EL based marketed formulation were evaluated. METHODS: Paclitaxel elastic liposomal formulations were prepared and characterized in vitro, ex-vivo and in vivo. Single dose toxicity study of paclitaxel elastic liposomal and marketed formulation was carried out in dose range of 10, 20, 40, 80, 120, 160 and 200 mg/kg. Cytotoxicity of developed formulation was evaluated using small cell lung cancer cell line (A549). Antitumor activity of developed formulation was compared with the marketed formulation using Cytoselect™ 96-well cell transformation assay. RESULTS: In vivo administration of paclitaxel elastic liposomal formulation into mice showed 6 fold increase in Maximum Tolerated Dose (MTD) in comparison to the marketed formulation. Similarly, LD50 (141.6 mg/kg) was also found to increase significantly than the marketed formulation (16.7 mg/kg). Result of antitumor assay revealed a high reduction of tumor density with paclitaxel elastic liposomal formulation. Reduction in hemolytic toxicity was also observed with paclitaxel elastic liposomal formulation in comparison to the marketed formulation. CONCLUSION: The carrier based approach for paclitaxel delivery demonstrated significant reduction in toxicity as compared to the Cremophor EL based marketed formulation following intra-peritoneal administration in mice model. The reduced toxicity and enhanced anti-cancer activity of elastic liposomal formulation strongly indicate its potential for safe and effective delivery of paclitaxel.
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Antineoplásicos Fitogénicos/administración & dosificación , Excipientes/química , Neoplasias Pulmonares/tratamiento farmacológico , Paclitaxel/administración & dosificación , Animales , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/toxicidad , Carcinoma de Células Pequeñas/tratamiento farmacológico , Carcinoma de Células Pequeñas/patología , Línea Celular Tumoral , Ácido Desoxicólico/química , Relación Dosis-Respuesta a Droga , Femenino , Glicerol/análogos & derivados , Glicerol/química , Humanos , Dosificación Letal Mediana , Liposomas , Neoplasias Pulmonares/patología , Masculino , Dosis Máxima Tolerada , Ratones , Paclitaxel/farmacología , Paclitaxel/toxicidad , Fosfatidilcolinas/química , Glycine max/químicaRESUMEN
The objective of the study was to develop a mathematical model for predicting the disintegration time of fast disintegrating tablets (FDTs) by estimating the powder characteristics of powder blend prior to compression. A combination of chitosan-alginate complex and glycine in the ratio of 50:50 was used for preparing FDTs. The developed mathematical model allowed water sorption time (WST), effective pore radius (R(eff.p)) and swelling Index (SI) of powder mixture as well as tablet crushing strength to be successfully correlated with disintegration time (DT) of FDTs. The predicted model showed that disintegration time of FDTs to be directly correlated with powder characteristics and inversely correlated with tablet crushing strength. Furthermore, a correlation of 0.97 was obtained when DT of FDTs was compared with SI/(WST * R(eff.p)). This correlation was not affected by inclusion of water soluble (ondansetron hydrochloride or metaclopramide hydrochloride) or water insoluble (domperidone) drugs in the powder blend or FDTs. These observations indicated the versatility of the mathematical model in predicting the disintegration time of FDTs by evaluating the selected characteristics of the powder blends without actually preparing the FDTs.
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Modelos Químicos , Polvos/química , Comprimidos/química , Adsorción , Química Farmacéutica , Quitosano/química , Fuerza Compresiva , Domperidona/administración & dosificación , Domperidona/química , Estabilidad de Medicamentos , Excipientes/química , Glicina/química , Metoclopramida/administración & dosificación , Metoclopramida/química , Ondansetrón/administración & dosificación , Ondansetrón/química , Solubilidad , Factores de Tiempo , AguaRESUMEN
Spectrofluorimetric and high-performance liquid chromatography methods for estimation of repaglinide were developed. These methods were validated for estimation of repaglinide in tablets as well as in receptor fluid obtained during in vitro permeation studies. Repaglinide was observed to exhibit emission and excitation wavelengths, respectively, at 379 nm and 282 nm with linearity in the concentration range of 5-80 µg/ml. High-performance liquid chromatography analysis of repaglinide yielded retention time of 6.14 min with linearity ranging from 0.1-1.2 µg/ml concentration. Spectrofluorimetric analysis of repaglinide in tablets yielded results comparable to high performance liquid chromatography.
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In the past years, alternative pharmaceutical formulations of anti-cancer agents have been investigated in order to improve conventional chemotherapy treatment. In conventional/current therapy oral tablet, capsule and injectable formulations are used for anti-cancer drugs delivery. These formulations associated with problems like severe toxic side effects on healthy organs, difficulties in clinical administration, drug resistance and limited access of the drug to the tumor sites suggested the need to focus on site specific controlled drug delivery systems. Novel drug delivery systems are capable of controlling the rate of drug delivery, sustaining the duration of therapeutic activity and targeting the drug to the disease tissue leading to better therapeutic effect with minimum side effects. In this review, we have explored the literature related to recent development in delivery of anti-cancer drugs identify problems in present conventional chemotherapy and detailed newer approaches and future development in the delivery of anti-cancer drugs.
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Antineoplásicos/administración & dosificación , Química Farmacéutica/métodos , Preparaciones de Acción Retardada/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Animales , Antineoplásicos/farmacocinética , Química Farmacéutica/tendencias , Sistemas de Liberación de Medicamentos/tendencias , Humanos , Modelos BiológicosRESUMEN
The present study was aimed at evaluating the possible use of inter polymer complexed (IPC) films of xanthan gum (XG) and cationic guar gum (CGG) for formulating domperidone bioadhesive films. Formation of bonds between -COO¯ groups of XG and -N(+)(CH(3))(3) groups of CGG was evident in the FTIR spectra of IPC films. Bioadhesive strength of the films was evaluated employing texture analyser. Water uptake studies indicated swelling to be a function of XG concentration in the interpolymer complexes. The bioadhesive films were found to possess neutral pH. In vitro drug release studies and residence time studies indicated that the film comprising CGG:XG (80:20) released 98% of domperidone in 8 h and exhibited a residence time of approximately 8 h. Enhanced bioavailability of domperidone was observed from bioadhesive films as compared to orally administered conventional tablets. Overall, the findings suggest that IPC films of XG and CGG, exhibiting desired bioadhesive strength and enhanced bioavailability of domperidone, can be prepared.
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The present study was aimed at in vitro and in vivo evaluation of PEGylated elastic liposomal formulation for lymphatic targeting of zidovudine (AZT). PEGylated elastic liposomal formulation was prepared and characterized for characteristic in vitro, ex-vivo and in vivo parameters. The plain and PEGylated elastic liposomal formulation showed transdermal flux of 99.8+/-5.8 and 119.5+/-5.2 microg/cm(2)/hr, respectively across the rat skin. Results of biodistribution study indicated 27-fold higher accumulation of AZT in lymphoid tissues after application of PEGylated elastic liposomes as compared to free drug. The efficient localization of elastic liposomal formulation in lymphatic system is of particular interest for HIV therapy, taking in account that replication of HIV mainly takes place in the lymphoid system. The Cellular uptake studies showed significantly higher cellular uptake in lymphoid cells (MT-2 cell line) from PEGylated elastic liposomal formulation (88.9+/-8.7%) in comparison to phosphate buffer saline (PBS, pH 7.4) solution of drug (27.1+/-2.8%). The entrapment of AZT into PEGylated elastic liposomes represents a potential approach for overcoming the toxicity by its selective uptake in lymphoid organs. This represents attractive approach for sustained and targeted delivery of AZT.
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Fármacos Anti-VIH/administración & dosificación , Tejido Linfoide/metabolismo , Zidovudina/administración & dosificación , Animales , Fármacos Anti-VIH/química , Fármacos Anti-VIH/farmacocinética , Línea Celular , Química Farmacéutica , Estabilidad de Medicamentos , Liposomas , Polietilenglicoles/administración & dosificación , Ratas , Ratas Sprague-Dawley , Absorción Cutánea , Zidovudina/química , Zidovudina/farmacocinéticaRESUMEN
The present study was aimed at unveiling the influence of glycyrrhizin and chitosan on rat epidermis and to correlate these effects with percutaneous permeation characteristics of carvedilol. The permeation of carvedilol across excised rat epidermis was significantly higher (p < 0.05) when glycyrrhizin, chitosan, or glycyrrhizin-chitosan mixture was used as a donor vehicle as compared to propylene glycol:ethanol (7:3) mixture. Epidermis obtained after 12 hr treatment of viable rat skin with a glycyrrhizin-chitosan mixture showed significantly higher (p < 0.05) permeability to carvedilol as compared to that after treatment with glycyrrhizin or chitosan alone. Further, the application of patches containing glycyrrhizin-chitosan mixture resulted in sustained release of carvedilol, which was able to control the hypertension in deoxycorticosterone acetate induced hypertensive rats through 28 hr. Estimation of microconstituents in rat epidermis revealed maximum extraction of cholesterol, sphingosine, and triglycerides after treatment with glycyrrhizin-chitosan mixture. This was manifested in altered lipid and protein-specific thermotropic transitions. Further, increase in intercellular space, disordered lipid structure and corneocyte detachment as observed in SEM and TEM suggests great potential of glycyrrhizin for use as a percutaneous permeation enhancer.