Gopal Rai

Eudragit-coated pectin microspheres of 5-fluorouracil for colon targeting.

An objective of the present investigation was to prepare and evaluate Eudragit-coated pectin microspheres for colon targeting of 5-fluorouracil (FU). Pectin microspheres were prepared by emulsion dehydration method using different ratios of FU and pectin (1:3 to 1:6), stirring speeds (500–2000 rpm) and emulsifier concentrations (0.75%–1.5% wt/vol). The yield of preparation and the encapsulation efficiencies were high for all pectin microspheres. Microspheres prepared by using drug:polymer ratio 1:4, stirring speed 1000 rpm, and 1.25% wt/vol concentration of emulsifying agent were selected as an optimized formulation. Eudragit-coating of pectin microspheres was performed by oil-in-oil solvent evaporation method using coat: core ratio (5:1). Pectin microspheres and Eudragit-coated pectin microspheres were evaluated for surface morphology, particle size and size distribution, swellability, percentage drug entrapment, and in vitro drug release in simulated gastrointestinal fluids (SGF). The in vitro drug release study of optimized formulation was also performed in simulated colonic fluid in the presence of 2% rat cecal content. Organ distribution study in albino rats was performed to establish the targeting potential of optimized formulation in the colon. The release profile of FU from Eudragit-coated pectin microspheres was pH dependent. In acidic medium, the release rate was much slower; however, the drug was released quickly at pH 7.4. It is concluded from the present investigation that Eudragit-coated pectin microspheres are promising controlled release carriers for colon-targeted delivery of FU.

Development and characterization of hyaluronic acid decorated PLGA nanoparticles for delivery of 5-fluorouracil

The present investigation was aimed to develop and explore the prospective of engineered PLGA nanoparticles as vehicles for targeted delivery of 5-fluorouracil (5-FU). Nanoparticles of 5-FU-loaded hyaluronic acid-poly(ethylene glycol)-poly(lactide-co-glycolide) (HA-PEG-PLGA-FU) copolymer were prepared and characterized by FTIR, NMR, transmission electron microscopy, particle size analysis, DSC, and X-ray diffractometer measurement studies. The nanoparticulate formulation was evaluated for in vitro release, hemolytic toxicity, and hematological toxicity. Cytotoxicity studies were performed on Ehrlich ascites tumor (EAT) cell lines using MTT cell proliferation assay. Biodistribution studies of 99mTc labeled formulation were conducted on EAT-bearing mice. The in vivo tumor inhibition study was also performed after i.v. administration of HA-PEG-PLGA-FU nanoparticles. The HA conjugated formulation was found to be less hemolytic but more cytotoxic as compared to free drug. The hematological data suggested that HA-PEG-PLGA-FU formulation was less immunogenic compared to plain drug. The tissue distribution studies displayed that HA-PEG-PLGA-FU were able to deliver a higher concentration of 5-FU in the tumor mass. In addition, the HA-PEG-PLGA-FU nanoparticles reduced tumor volume significantly in comparison with 5-FU. Thus, it was concluded that the conjugation of HA imparts targetability to the formulation, and enhanced permeation and retention effect ruled out its access to the non-tumor tissues, at the same time favored selective entry in tumors, thereby reducing the side-effects both in vitro and in vivo.

Eudragit-coated dextran microspheres of 5-fluorouracil for site-specific delivery to colon

Abstract Objective of the present investigation was to prepare and evaluate the potential of enteric coated dextran microspheres for colon targeting of 5-fluorouracil (5-FU). Dextran microspheres were prepared by emulsification-crosslinking method and the formulation variables studied included different molecular weights of dextran, drug:polymer ratio, volume of crosslinking agent, stirring speed and time. Enteric coating (Eudragit S-100) of dextran microspheres was performed by oil-in-oil solvent evaporation method using different coat:core ratios (4:1 or 8:1). Uncoated and coated dextran microspheres were characterized by particle size, surface morphology, entrapment efficiency, DSC, in vitro drug release in the presence of dextranase and 2% rat cecal contents. The release study of 5-FU from coated dextran microspheres was pH dependent. No release was observed at acidic pH; however, the drug was released quickly where Eudragit starts solublizing there was continuous release of drug from the microspheres. Organ distribution study was suggested that coated dextran microspheres retard the release of drug in gastric and intestinal pH environment and released of drug from microspheres in colon due to the degradation of dextran by colonic enzymes.

Preliminary investigation for wound healing and anti-inflammatory effects of Bambusa vulgaris leaves in rats.

Background Bambusa vulgaris (Family: Poaceae) used in Ayurveda for paralytic complaints, inflammatory disorders and externally to skin disorders. It has various medicinal uses with good nutritional composition and a rich source of vitamins, proteins, amino acid, beta-carotene and phenolic compounds. Objective The present study was aimed to evaluate wound healing and anti-inflammatory potential of ethanol extract of B. vulgaris leaves in rats. Materials and methods The B. vulgaris leaves were evaluated for wound healing on incision and excision wound methods. Anti-inflammatory effect was evaluated by measurement of paw edema in carrageenan-induced inflammation in rats. Ethyl acetate (BVL-A) and aqueous (BVL-B) fractions from the ethanol extract of leaves were screened for wound healing effects by measuring tensile strength and biochemical parameters in incision wound method. The wound contraction area, antioxidant status and histopathological studies were done in excision wound method. Results Tensile strength and hydroxyproline level of 5% w/w ointment of BVL-A and BVL-B treated groups were found significantly (P < 0.01) higher and comparable to the reference group. The histopathological study showed the proliferation of collagen, fibrous tissue, and capillaries with epidermal covering at the margin of the wound. The percent inhibition of paw edema was significantly decrease by increasing concentration of BVL-A and BVL-B fractions. In addition, it was found that B. vulgaris possesses antioxidant properties, by its ability to increase antioxidants level. Conclusions The results obtained in the present study were indicated that ethyl acetate fraction of B. vulgaris leaves inhibits paw edema and accelerates cutaneous wound healing.

In-vitro and in-vivo assessment of dextran-appended cellulose acetate phthalate nanoparticles for transdermal delivery of 5-fluorouracil

Abstract The aim of this research was transdermal delivery of 5-fluorouracil (5-FU) using dextran-coated cellulose acetate phthalate (CAP) nanoparticulate formulation. CAP nanoparticles were prepared using drug-polymer ratio (1:1 to 1:3) and surfactant ratio (2.5, 5 and 10%). Dextran coating was made using aminodextran. The results showed that the optimized CAP nanoparticles (CNs) and dextran-coated CAP nanoparticles represented core-corona nanoparticles with the mean diameter of 75 ± 3 and 79 ± 2 nm, respectively, and entrapment efficiency was 82.5 ± 0.06 and 78.2 ± 0.12, respectively. Dextran-coated nanoparticles (FDCNs) and CAP nanoparticles (FCNs) showed in vitro 5-FU release upto 31 h and 8 h, respectively. Moreover, the cumulative amount of 5-FU penetrated through excised skin from FDCNs was 2.94 folds than that of the FU cream. Concentration of 5-FU in epidermis and dermis were also studied. In dermis, concentration of 5-FU was found higher in case of FDCN formulation than plain FU cream. FDCNs were found more hemocompatible in comparison to FCNs. The hematological data recommended that FDCNs formulation was less immunogenic compared to FU creams formulation. In blood level study, FDCNs exhibited 153, 12, 16.66 and 16.24-fold higher values for area under the curve, Tmax, Cmax and mean residence time (MRT) compared with those of FU cream, respectively. The in-vitro cytotoxicity was assessed using the MCF-7 by the MTT test and was compared to the plain 5-FU solution. All the detailed evidence showed that FDCNs could provide a promising tuning as a transdermal delivery system of 5-FU.

Hyaluronic acid embedded cellulose acetate phthlate core/shell nanoparticulate carrier of 5-fluorouracil

Aim of this research was to prepare hyaluronic acid-modified-cellulose acetate phthalate (HAC) core shell nanoparticles (NPs) of 5-fluorouracil (5-FU). HAC copolymer was synthesized and confirmed by fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy. HAC NPs with 5-FU were prepared using HAC copolymer and compared with 5-FU loaded cellulose acetate phthalate (CAP) NPs. NPs were characterized by atomic force microscopy (AFM), particle size, zeta potential, polydispersity index, entrapment efficiency, in-vitro release, differential scanning calorimetry (DSC) and X-ray diffraction (XRD). HAC NPs were found slower release (97.30% in 48h) than (99.25% in 8h) CAP NPs. In cytotoxicity studies, showed great cytotoxic potential of 5-FU loaded HAC NPs in A549, MDA-MD-435 and SK-OV-3 cancer cellline. HAC NPs showing least hemolytic than CAP NPs and 5-FU. Area under curve (AUC), maximum plasma concentration (Cmax), mean residence time (MRT) and time to reach maximum plasma concentration Tmax), were observed 4398.1±7.90μgh/mL, 145.45±2.25μg/L, 45.74±0.25h, 72±0.50h, respectively of HAC NPs and 119.92±1.78μgh/mL, 46.38±3.42μg/L, 1.2±0.25h, 0.5±0.02h were observed in plain 5-FU solution. In conclusion, HAC NPs is effective deliver carrier of 5-FU for lung cancer.

Enteric-coated epichlorohydrin crosslinked dextran microspheres for site-specific delivery to colon

Abstract Enteric-coated epichlorohydrin crosslinked dextran microspheres containing 5-Fluorouracil (5-FU) for colon drug delivery was prepared by emulsification-crosslinking method. The formulation variables studied includes different molecular weights of dextran, volume of crosslinking agent, stirring speed, time and temperature. Dextran microspheres showed mean entrapment efficiencies ranging between 77 and 87% and mean particle size ranging between 10 and 25 µm. About 90% of drug was released from uncoated dextran microspheres within 8 h, suggesting the fast release and indicated the drug loaded in uncoated microspheres, released before they reached colon. Enteric coating (Eudragit-S-100 and Eudragit-L-100) of dextran microspheres was performed by oil-in-oil solvent evaporation method. The release study of 5-FU from coated dextran microspheres was complete retardation in simulated gastric fluid (pH 1.2) and once the coating layer of enteric polymer was dissolved at higher pH (7.4 and 6.8), a controlled release of the drug from the microspheres was observed. Further, the release of drug was found to be higher in the presence of dextranase and rat caecal contents, indicating the susceptibility of dextran microspheres to colonic enzymes. Organ distribution and pharmacokinetic study in albino rats was performed to establish the targeting potential of optimized formulation in the colon.

Study of Antimicrobial and Cytotoxic Potential of the Oyster Mushroom Pleurotus ostreatus cv. Florida (Agaricomycetes).

This work was undertaken to evaluate in vitro antimicrobial and cytotoxic potential of Pleurotus ostreatus cv. Florida. Mushroom basidiocarps were extracted in water:ethanol (1:1, v/v), and the resulting extract was subjected to antimicrobial studies against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella oxytoca, Bacillus subtilis, and Candida albicans. Cytotoxic potential on viable human leukocytes was studied. In vitro results showed excellent antimicrobial and cytotoxic potentials of the mushroom extract. Thus, functional properties of P. ostreatus cv. Florida could be used in the search for novel therapeutics.

Protective Effects of Tridax procumbens Linn. Leaves on Experimentally Induced Gastric Ulcers in Rats

The gastroprotective activity of ethanol extract of Tridax procumbens leaves was evaluated in rats. Luteolin, a flavonoid, was isolated from ethanol extract of T. procumbens by column chromatography. Gastric ulcers were induced by ethanol and indomethacin in rats, and the ulcer index, percent inhibition, gastric content, and total acidity on the gastric lesions were determined. The phytochemical study revealed the presence of flavonoids, glycosides, proteins, and tannins in the ethanol extract. The total flavonoid content was found to be 142.6 ± 6.38 mg·(100 gm)−1 of ethanol extract. The ethanol extract with 400 mg·kg−1 produced dose-dependent inhibition on the ulcer lesion index (9.76 ± 0.06), changes in the gastric volume (4.38 ± 0.89), and pH (4.8 ± 0.88) in ethanol-induced ulcer. The ethanol extract at 400 mg·kg−1 also restored superoxide dismutase (SOD), reduced glutathione (GSH), catalase level in rat stomach, and large fibroblast cells in histology that support the protective effects.