Acute and sub chronic toxicity studies with herbal pain relieving formula (Rhuleave-K™) in rats.

Rhuleave-K™ is a proprietary combination of Curcuma longa extract, Boswellia serrata extract and black sesame seed oil. Acute toxicity was evaluated as per OECD guidelines 423. Rhuleave-K™ was fed at 2000 mg/kg to overnight fasted female rats. Clinical signs of abnormality and mortality was observed daily for 14 days. Sub-chronic toxicity was studied by feeding Rhuleave-K™ at 100, 500 and 1000 mg/kg/day to rats as per OECD guidelines 408. After 90 days feeding, hematological and biochemical parameters were analyzed. Histopathology of all the major organs was also studied. In the acute toxicity study, there was no clinical sign of toxicity in any of the rats at maximum dose of 2000 mg/kg. The LD50 was computed as >2000 mg/kg in rats. The repeated dosing of Rhuleave-K™ at the maximum dose level of 1000 mg/kg for 90 days did not induce any observable toxic effects in rats, when compared to its corresponding control. The hematology and biochemistry profiles of treated rats were similar to control animals and difference was non-significant (p > 0.05). The histopathology of major organs of all the control and treated animals was normal. In this study the NOAEL for Rhuleave-K™ was calculated as 1000 mg/kg daily in rats.

Galactose decorated PLGA nanoparticles for hepatic delivery of acyclovir.

The present study explores prospective of surface tailored nanoparticles for targeted delivery of acyclovir along with the interception of minimal side effects. Acyclovir loaded plain and galactosylated poly lectic co glycolic acid (PLGA) nanoparticles were efficiently prepared and characterized by Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), size, polydispersity index, zeta potential, and entrapment efficiency. The formulations were evaluated for in vitro drug release and hemolysis. Further, biodistribution study and fluorescent microscopic studies were carried out to determine the targeting potential of formulations. SEM revealed smooth morphology and spherical shape of the nanoparticles. In vitro, the galactosylated nanoparticles were found to be least hemolytic and exhibited a sustained release pattern. In vivo studies exhibited an augmented bioavailability, increased residence time and enhanced delivery of acyclovir to the liver upon galactosylation. It may therefore be concluded that galactose conjugated PLGA nanoparticles can be used suitably as vehicles for delivery of bioactives specifically to the hepatic tissues and may be thus exploited in the effective management of various liver disorders.

Development and characterization of phyto-vesicles of wedelolactone for hepatoprotective activity.

Wedelolactone is isolated from the dried leaves of Eclipta alba (L.) and reported to be effective as a potential hepatoprotective, antibacterial and anti hemorrhagic. Pharmacokinetic studies of wedelolactone reveal its poor absorption through the intestine. The objective of the present study is to enhance bioavailability of wedelolactone by its complexation with phosphatidyl choline and then formulating it as phyto-vesicles for hepatoprotective activity. The complex of wedelolactone rich fraction was prepared with phosphatidyl choline and characterized on the basis of solubility, melting point, thin layer chromatography (TLC), UV, IR and NMR spectroscopy. The complex was further converted into phyto-vesicles and characterized. The hepatoprotective potential of phyto-vesicles was compared with complex, wedelolactone rich fraction and physical mixture of wedelolactone rich fraction and phosphatidyl choline by in vitro method. The results revealed that hepatoprotective activity is better in case of phyto-vesicles as compared to the complex, physical mixture and the wedelolactone itself. Enhanced bioavailability of the wedelolactone complex may be due to the amphiphillic nature of the complex, which greatly enhance the water and lipid solubility of the compound. The present study clearly indicates the superiority of phyto-vesicles over the complex and wedelolactone, in terms of better absorption and improved hepatoprotective activity.

Microemulsion-loaded hydrogel formulation of butenafine hydrochloride for improved topical delivery.

Topical microemulsion systems for the antifungal drug, butenafine hydrochloride (BTF) were designed and developed to overcome the problems associated with the cutaneous delivery due to poor water solubility. The solubility of BTF in oils, surfactants and co-surfactants was evaluated to screen the components of the microemulsion. Isopropyl palmitate was used as the oil phase, aerosol OT as the surfactant and sorbitan monooleate as co-surfactant. The pseudoternary diagrams were constructed to identify the area of microemulsion existence and optimum systems were designed. The systems were assessed for drug-loading efficiency and characterized for pH, robustness to dilution, globule size, drug content and stability. Viscosity analysis, spreadability, drug content assay, ex vivo skin permeation study and antifungal activity assay were performed for the optimized microemulsion-loaded hydrogel. The optimized BTF microemulsion had a small and uniform globule size. The incorporation of microemulsion system into Carbopol 940 gel was found to be better as compared to sodium alginate or hydroxyl propyl methyl cellulose (HPMC K4 M) gel. The developed gel has shown better ex vivo skin permeation and antifungal activity when compared to marketed BTF cream. Thus, the results provide a basis for the successful delivery of BTF from microemulsion-loaded hydrogel formulation, which resulted in improved penetration of drug and antifungal activity in comparison with commercial formulation of BTF.

Development and characterization of phyto-vesicles of ß-sitosterol for the treatment of androgenetic alopecia.

Alopecia is a psychologically distressing phenomenon. Androgenetic alopecia (AGA) is the most common form of alopecia, which affects millions of men and women worldwide, and is an androgen driven disorder. To study the effect of ß-sitosterol phyto-vesicles on AGA, the testosterone-induced alopecia model was used. For the study, the albino rats were used and the period of study was 21 days. ß-Sitosterol is a phytosterol which is chemically similar to cholesterol. This compound was found suitable for the preparation of phyto-vesicles by the process involving its complexation with phosphatidyl choline. Pharmacokinetic studies of ß-sitosterol reveal its poor absorption through the intestine. The objective of the present study is to enhance the bioavailability of ß-sitosterol by its complexation with phosphatidyl choline and then to formulate it as phyto-vesicles for the treatment of alopecia. The complex of ß-sitosterol was prepared with phosphatidyl choline and characterized on the basis of solubility, melting point, TLC, UV, IR and NMR spectroscopy. This complex was then formulated as phyto-vesicles and then characterized. The results revealed that effect on alopecia is better in case of phyto-vesicles as compared to the complex, physical mixture and the ß-sitosterol itself. Enhanced bioavailability of the ß-sitosterol complex may be due to the amphiphilic nature of the complex, which greatly enhance the water and lipid solubility of the compound. The present study clearly indicates the superiority of phyto-vesicles over the complex and ß-sitosterol, in terms of better absorption and improved activity for the treatment of alopecia.

Absorption enhancement of grape seed polyphenols by complexation with phosphatidyl choline.

Grape seed polyphenols (GPP) are reported to have various biological effects along with strong antioxidant potential. Pharmacokinetic studies of GPP reveal its poor absorption through the intestine. The objective of the present study was to enhance bioavailability of GPP by its complexation with phosphatidyl choline. A complex of GPP was prepared with phosphatidyl choline and characterized on the basis of solubility, melting point, DSC, and IR. Everted intestine sac technique was used to study ex vivo drug absorption of GPP-PC complex and plain GPP. Pharmacokinetic studies were performed in rats and the hepatoprotective activity of GPP-PC complex was also compared with GPP and GPP-PC physical mixture in isolated rat hepatocytes. Analytical reports along with spectroscopic data revealed the formation of the complex. The results of ex vivo study show that the GPP-PC complex has significantly increased absorption compared with GPP, when given in equimolar doses. The complex showed enhanced bioavailability, improved pharmacokinetics, and increased hepatoprotective activity as compared to GPP or GPP-PC physical mixtures. Enhanced bioavailability of GPP-PC complex may be due to the amphiphilic nature of the complex, which greatly enhance the lipid miscibility of GPP. The present study clearly indicates the superiority of complex over GPP, in terms of better absorption, enhanced bioavailability, and improved pharmacokinetics.

Bioavailability enhancement of curcumin by complexation with phosphatidyl choline.

Curcumin is a major constituent of rhizomes of Curcuma longa. Pharmacokinetic studies of curcumin reveal its poor absorption through intestine. Objective of the present study was to enhance bioavailability of curcumin by its complexation with phosphatidyl choline (PC). Complex of curcumin was prepared with PC and characterized on the basis of solubility, melting point, differential scanning calorimetry, thin layer chromatography, and infrared spectroscopic analysis. Everted intestine sac technique was used to study ex vivo drug absorption of curcumin-PC (CU-PC) complex and plain curcumin. Pharmacokinetic studies were performed in rats, and hepatoprotective activity of CU-PC complex was also compared with curcumin and CU-PC physical mixture in isolated rat hepatocytes. Analytical reports along with spectroscopic data revealed the formation of complex. The results of ex vivo study show that CU-PC complex has significantly increased absorption compared with curcumin, when given in equimolar doses. Complex showed enhanced bioavailability, improved pharmacokinetics, and increased hepatoprotective activity as compared with curcumin or CU-PC physical mixture. Enhanced bioavailability of CU-PC complex may be due to the amphiphilic nature of the complex, which greatly enhance the water and lipid solubility of the curcumin. The present study clearly indicates the superiority of complex over curcumin, in terms of better absorption, enhanced bioavailability, and improved pharmacokinetics.

Development and evaluation of vesicular system for curcumin delivery.

Creams and gels containing curcumin are popularized worldwide and marketed all over the world, but even after incorporation of high amount of curcumin in topical formulations, significant antioxidant and anti-aging effect could not be achieved. Objective of the present study was to develop vesicular system for delivery of curcumin to achieve enhanced topical bioavailability. Complex of curcumin with phosphatidyl choline (PC) was prepared and characterized on the basis of TLC, DSC, melting point and IR spectroscopic analysis. The complex was further converted into vesicles (phyto-vesicles). Liposomes and niosomes of curcumin were also prepared and all these vesicular formulations were incorporated into carbopol gel to make feasible for topical application on skin. Anti-aging effects of these formulations were compared with plain curcumin and physical mixture of curcumin with phosphatidyl choline in UV-induced oxidative stress in mice. Analytical reports along with spectroscopic data revealed the formation of the complex. In the present study, the phyto-vesicles were found to be most effective than all other formulations and plain curcumin in providing enhanced antioxidant and antiaging effect. This increase may be due to the amphiphilic nature of the complex, which greatly enhances the water and lipid miscibility of the curcumin. This study clearly indicates the superiority of CU-PC complex and the phyto-vesicles prepared from CU-PC complex over others in providing enhanced anti-aging, antioxidant and anti-wrinkle effect.

Complexation with phosphatidyl choline as a strategy for absorption enhancement of boswellic acid.

Boswellic acids (BAs) are isolated from oleo gum resin of Boswellia serrata and are reported to be effective as anti-inflammatory, hypolipidemic, immunomodulatory, and anti-tumor. Pharmacokinetic studies of boswellic acid reveal its poor absorption through the intestine. The objective of the present study is to enhance bioavailability of boswellic acid by its complexation with phosphatidylcholine. A complex of boswellic acid was prepared with phosphatidylcholine and characterized on the basis of solubility, melting point, TLC, and IR. An everted intestine sac technique was used to study ex-vivo drug absorption of boswellic acid-phosphatidylcholine (BA-PC) complex and plain boswellic acid. Anti-inflammatory activity of the complex was compared with boswellic acid in carrageenan-induced paw edema in rats. Hypolipidemic activity was also evaluated in Triton-induced hyperlipidemia. The complex was also converted into vesicles (phytosomes) and compared with other vesicular systems (liposomes and niosomes) by evaluating its anti-inflammatory effect. Analytical reports along with spectroscopic data revealed the formation of a complex. The results of ex-vivo study show that BA-PC complex has significantly increased absorption compared with boswellic acid, when given in equimolar doses. The complex showed better anti-inflammatory and hypolipidemic activity as compared to BA. Among all vesicular systems phytosomes showed maximum anti-inflammatory activity. Enhanced bioavailability of the BA-PC complex may be due to the amphiphilic nature of the complex, which greatly enhance the water and lipid solubility of the boswellic acid. The present study clearly indicates the superiority of complex over boswellic acid, in terms of better absorption, enhanced bioavailability and improved pharmacokinetics.

Evaluation of hepatoprotective activity of Cleome viscosa Linn. extract.

OBJECTIVES: To evaluate the hepatoprotective activity of ethanolic extract of Cleome viscosa Linn. (Capparidaceae) against carbon tetrachloride (CCI(4)) induced hepatotoxicity in experimental animal models. MATERIALS AND METHODS: Leaf powder of Cleome viscosa was extracted with ethanol. The hepatoprotective activity of the extract was assessed in CCI(4) induced hepatotoxicity in rats. Various biochemical parameters were estimated and histopathological studies were also performed on rat liver. The hepatoprotective activity was also supported by determining a functional parameter, i.e. thiopental-induced sleep of mice poisoned with CCl(4). RESULTS: The test material was found effective as hepatoprotective, through in vivo and histopathological studies. The extract was found to be effective in shortening the thiopental induced sleep in mice poisoned with CCl(4). The hepatoprotective effect of ethanolic extract was comparable to that of silymarin, a standard hepatoprotective agent. CONCLUSION: The results of the present study show that ethanolic extract of Cleome viscosa has significant hepatoprotective activity.

Hepatoprotective activity of Cleome viscosa Linn. extract against thioacetamide-induced hepatotoxicity in rats.

Cleome viscosa Linn. (Family Capparidaceae) is naturalised throughout the hot and moist parts of India. Fresh leaves of this plant are used very effectively for the treatment of jaundice in the folk medicines of the Bundelkhand region of India. The hepatoprotective activity of the ethanolic extract of leaves was investigated against thioacetamide-induced hepatotoxicity in rats. The test material was found to be effectively hepatoprotective, as evidenced by biochemical parameters and histopathological studies. The hepatoprotective effect of ethanolic extract was comparable to that of silymarin, a standard hepatoprotective agent. The results of the present study support the traditional beliefs of the hepatoprotective effects of C. viscosa Linn.