Shrestha Sharma

Rutin : therapeutic potential and recent advances in drug delivery.

Introduction: Natural compounds such as bioflavonoids have found application in health care system due to their wide biological activities, high safety margins and lower cost. Rutin, a polyphenolic bioflavonoid has shown wide range of pharmacological applications due to its significant antioxidant properties. Conventionally, it is used as antimicrobial, antifungal, and antiallergic agent. However, current research has shown its multispectrum pharmacological benefits for the treatment of various chronic diseases such as cancer, diabetes, hypertension and hypercholesterolemia. Its use is advantageous over other flavonoids as it is a nontoxic and nonoxidizable molecule. Areas covered: This review focus on various studies done on rutin explaining its broad spectrum pharmacological activities. In addition, this review will also focus on the challenges associated with the drug and various approaches to improve the oral bioavailability of rutin. Expert opinion: Rutin is a highly potent molecule due to its strong antioxidant properties. In the near future, enhancing its bioavailability using novel drug delivery methods having minimum side effects will bring this promising natural molecule to the forefront of therapy for the treatment of various chronic human diseases.

Resveratrol: review on therapeutic potential and recent advances in drug delivery

Introduction: Natural products have seen a wide range of acceptability for the prevention and treatment of diseases throughout history. Resveratrol, a member of the stilbene family, has been found to potentially exhibit anticancer, antiangiogenic, immunomodulatory and cardioprotective activities as well as being an antioxidant. This is in addition to its usefulness in the treatment of neurodegenerative disease, diabetes and cardiac ailments. Currently, various studies have revealed that resveratrol is a potential drug candidate with multi-spectrum therapeutic application. Areas covered: This review aims to describe the various studies supporting the wide range of pharmacological activities of resveratrol. In addition, it includes a section devoted to discussing the challenges associated with the drug and strategies to improve the properties of resveratrol such as solubility, stability and bioavailability. Expert opinion: Resveratrol demonstrated its ability to be a potential drug candidate for the treatment of different ailments due to its potent antioxidant properties. To improve the drug stability, increase the bioavailability and minimize side-effects of resveratrol, novel drug delivery systems have been formulated to bring this potential candidate to the first line of disease treatment.

Nanocarrier-based hydrogel of betamethasone dipropionate and salicylic acid for treatment of psoriasis

Introduction: Betamethasone dipropionate (BD) has anti-inflammatory, immunomodulatory, and antiproliferative activity. The aim of the current work was to test the hypothesis that the addition of corticosteroid such as BD and a keratolytic agent such as salicylic acid in nanocarrier based microemulsions formulation would result in enhancement and sustaining of corticosteroid delivery rate leading to better anti-psoriatic activity. Clinical use of BD is restricted to some extent due to its poor permeability across the skin. So to increase its permeation across the skin, microemulsion-based gel formulations were prepared and characterised. Materials and Methods: Microemulsions were prepared by aqueous phase titration method, using oleic acid:sefsol (1.5:1), Tween 20, isopropyl alcohol, and distilled water as the oil phase, surfactant, cosurfactant and aqueous phase, respectively. Selected formulations were subjected to physical stability studies and consequently in vitro skin permeation studies. Surface studies of optimized formulation were done by transmission electron microscopy. In vivo anti-inflammatory activity was done by carageenan-induced raw paw edema method. Results: The droplet size of microemulsions ranged from 60 to 190 nm. The optimized formulation exhibited viscosity 28.55 ± 2.03 mP, refractive index 1.409, pH 6.4, and conductivity 10-4 scm-1. The optimized microemulsion was converted into hydrogel using carbopol 934, and salicylic acid was incorporated into it. Drug deposition in skin was found to be 29.73 μg/mg. Assessment of skin permeation was done by histopathology studies which indicated changes in the structure of epidermal membrane of skin. In vivo anti-inflammatory activity indicated 72.11% and 43.96% inhibition of inflammation in case of developed microemulsion gel and marketed gel, respectively. Conclusions: The developed microemulsion gel containing BD and salicylic acid provided sustained and good anti-inflammatory activity for the treatment of psoriasis.

Effect of high-pressure homogenization on formulation of TPGS loaded nanoemulsion of rutin – pharmacodynamic and antioxidant studies

Abstract Polyphenolic bioflavonoid, Rutin possesses wide range of pharmacological activities. However, it shows poor bioavailability when administered orally. The aim of this study was to formulate and compare the potential of nanoemulsions for the solubility enhancement of rutin (RU) by using different techniques. RU-loaded nanoemulsions were prepared by spontaneous emulsification method and high-pressure homogenization (HPH) technique using sefsol 218 and tocopheryl polyethylene glycol 1000 succinate (TPGS) (1:1), solutol HS15 andtranscutol P as oil phase, surfactant and co-surfactant, respectively. The prepared formulations were compared for various parameters like droplet size, percentage transmittance, zeta potential, viscosity, refractive index and in vitro release. The HPH nanoemulsions showed smaller droplet size and increased in vitro release when compared to nanoemulsions prepared by spontaneous emulsification method. The optimized formulation showed spherical globules with average globule diameter of 18 nm and zeta potential of −41 mV. Cumulative percentage drug released obtained for RU, PF6 (spontaneous emulsification formulation F6) and HF6 (HPH formulation F6) were 41.5 ± 0.04%, 49.5 ± 0.06% and 94.8 ± 0.03%, respectively, after 6 h. The permeability of RU from HF6 was found to be ≈4.6 times higher than RU suspension during ex vivo everted gut sac studies. Antioxidant activity was determined by using DPPH assay and reducing power assay method. Results showed a high scavenging efficiency toward DPPH radicals by HF6. Anti-inflammatory effect of RU as determined by carrageenan-induced rat paw edema method was found to be higher (75.2 ± 4.8%) when compared to RU suspension (46.56 ± 3.5%). It can be inferred that TPGS-loaded nanoemulsion of RU serve as an effective tool in increasing solubility and permeability of RU.

Synergistic antioxidant action of vitamin E and rutin SNEDDS in ameliorating oxidative stress in a Parkinson’s disease model

PURPOSE Oxidative stress is the leading cause in the pathogenesis of Parkinsons disease. Rutin is a naturally occurring strong antioxidant molecule with wide therapeutic applications. It suffers from the problem of low oral bioavailability which is due to its poor aqueous solubility. METHODS In order to increase the solubility self-nanoemulsifying drug delivery systems (SNEDDS) of rutin were prepared. The oil, surfactant and co-surfactant were selected based on solubility/miscibility studies. Optimization was done by a three-factor, four-level (34) Box-Behnken design. The independent factors were oil, surfactant and co-surfactant concentration and the dependent variables were globule size, self-emulsification time, % transmittance and cumulative percentage of drug release. The optimized SNEDDS formulation (RSE6) was evaluated for various release studies. Antioxidant activity was assessed by various in vitro tests such as 2,2-diphenyl-1-picrylhydrazyl and reducing power assay. Oxidative stress models which had Parkinsons-type symptoms were used to determine the antioxidant potential of rutin SNEDDS in vivo. Permeation was assessed through confocal laser scanning microscopy. RESULTS An optimized SNEDDS formulation consisting of Sefsol + vitamin E-Solutol HS 15-Transcutol P at proportions of 25:35:17.5 (w/w) was prepared and characterized. The globule size and polydispersity index of the optimized formulation was found to be 16.08 ± 0.02 nm and 0.124 ± 0.01, respectively. A significant (p < 0.05) increase in the percentage of drug release was achieved in the case of the optimized formulation as compared to rutin suspension. Pharmacokinetic study showed a 2.3-fold increase in relative oral bioavailability. The optimized formulation had significant in vitro and in vivo antioxidant activity. CONCLUSION Rutin SNEDDS have been successfully prepared and they can serve as an effective tool in enhancing the oral bioavailability and efficacy of rutin, thus helping in ameliorating oxidative stress in neurodegenerative disorders like Parkinsons disease.

Submicron Size Formulation of Linseed Oil Containing Omega-3 Fatty Acid for Topical Delivery

The aim of the present study was to design and develop topical submicron size gel formulation of linseed oil with enhanced permeation through the skin for the management of psoriasis. Linseed oil contains significant amount of α-linolenic acid (ALA) an omega-3 fatty acid, which is responsible for its pharmacological actions. In order to enhance permeation through skin, microemulsion based gel formulation was prepared and characterized. Microemulsions were prepared by aqueous phase titration method, using linseed oil, Unitop 100, PEG 400, and distilled water as the oil phase, surfactant, cosurfactant and aqueous phase, respectively. Selected formulations were subjected to physical stability studies and consequently in vitro skin permeation studies. Surface morphology studies of optimized formulation were done by transmission electron microscopy (TEM). The droplet size of microemulsions ranged from 70 to 500 nm with average particle size 186 nm. The optimized microemulsion was converted into hydrogel using carbopol 971 which had a viscosity of 498 ± 0.04 cps. During in vitro permeation study the flux of microemulsion formulation and gel was found to be 19.05 and 10.2 µg/cm2/hr, respectively, which indicated better penetration of linseed oil through the skin. These result indicated that the developed ME formulation may be a good approach for topical therapy for the management of psoriasis.