Nilakash Selkar

Tamoxifen nanostructured lipid carriers: enhanced in vivo antitumor efficacy with reduced adverse drug effects.

A novel approach of enhancing the Tamoxifen uptake via Intestinal Lymphatic System is executed by developing long chain lipid and oil based nanostructured lipid carrier system (Tmx-NLC). The aim was to achieve improved systemic bioavailability of Tamoxifen, prevent systemic and hepatotoxicity and enhance antitumor efficacy. Following the proof of concept achieved in cell culture experiments and in vivo pharmacokinetic and biodistribution study, the current work focuses on investigation of antitumor efficacy and treatment associated toxicity in murine mammary tumor mice model. The efficacy study demonstrated greater tumor suppression and 100% survival with 1.5 and 3 mg/kg Tmx-NLC compared to 3 mg/kg Tamoxifen suspension and Mamofen(®) (Khandelwal Pharmaceuticals, Mumbai, India). Tmx-NLC treatment for a month demonstrated improved systemic toxicity profile and no evidences of hepatotoxicity. Thus, developed Tmx-NLC could prove to be a promising delivery strategy to confer superior therapeutic efficacy and ability to address the biopharmaceutical and toxicity associated issues of drug.

Efficacy and safety of a herbo-mineral ayurvedic formulation 'Afrodet Plus(®)' in male rats.

Background: Reverse pharmacology for drug development has been highly productive and cost-effective in recent past as it is based on the documented therapeutic effects of plants in ancient texts. Afrodet Plus® is formulated for the treatment of male infertility, which contains ancient herbo-minerals. Its efficacy and safety are validated through this animal study in reverse pharmacology mode. Objectives: This study was undertaken to evaluate efficacy and safety of an Ayurvedic formulation Afrodet Plus® in adult male rats. Materials and Methods: Twelve male rats (Holtzman) between 8 and 10 weeks of age were randomly selected and animals were assigned to a control and two treatment groups. Dosing was performed daily. Various parameters such as weekly body weight, hematology, serum testosterone levels, epididymal sperm count, and efficiency of Daily Sperm Production (DSP) were evaluated. Results: It was found that epididymal sperm count had significantly increased in both low-dose (+27.39%) and high-dose (+40.5%) groups as compared to control group. The DSP also showed an increase of 43.7% at high dose of 180 mg/kg body weight as compared to the control group. An increase in sperm motility and especially progressive motility was observed when evaluated by Computer Assisted Semen Analyzer. Histological evaluation of testicular tissue for spermatogenic index revealed that the index had increased in treatment group as compared to control group. Conclusion: This study revealed that oral administration of Afrodet Plus® resulted in significant increase in DSP in the testis along with increase in epididymal sperm count and progressive motility as compared to control group without producing any treatment-related adverse effects. These findings provide the documentary evidence that the use of Afrodet Plus® at 90 and 180 mg/kg body weight is effective and safe for the treatment of male infertility especially to improve sperm count and progressive motility.

Fipronil-induced genotoxicity and DNA damage in vivo Protective effect of vitamin E

Fipronil, an insecticide of the phenylpyrazole class has been classified as a carcinogen by United States Environmental Protection Agency, yet very limited information is available about its genotoxic effects. Adult male and female animals were gavaged with various doses of fipronil (2.5, 12.5, and 25 mg/kg body weight (bw)) to evaluate micronucleus test (mice), chromosome aberration (CA), and comet assay (rats), respectively. Cyclophosphamide (40 mg/kg bw; intraperitoneal) was used as positive control. Another group of animals were pretreated with vitamin E orally (400 mg/kg bw) for 5 days prior to administration of fipronil (12.5 mg/kg). Fipronil exposure in both male and female mice caused significant increase in the frequency of micronuclei (MN) in polychromatic erythrocytes. Similarly, structural CAs in bone marrow cells and DNA damage in the lymphocytes was found to be significantly higher in the male and female rats exposed to fipronil as compared to their respective controls. The average degree of protection (male and female animals combined together) shown by pretreatment of vitamin E against fipronil-induced genotoxicity was 63.28%: CAs; 47.91%: MN formation; and 74.70%: DNA damage. Findings of this study demonstrate genotoxic nature of fipronil regardless of gender effect and documents protective role of vitamin E.

Comparative bone regeneration study of hardystonite and hydroxyapatite as filler in critical-sized defect of rat calvaria

There is a very significant and well-known clinical need for the development of new osteoinductive materials and the establishment of alternative therapies for the treatment of bone tissue loss or failure resulting from injury or disease as the transplantation of tissues in patients with these injury or disease is severely limited by donor scarcity and is highly associated to the risk of immune rejection and disease transfer. Herein, we studied in vivo bone response by quantifying efficacy and safety of three scaffold variations: (1) nanofibrous polycaprolactone (PCL), (2) PCL–hydroxyapatite (HA), and (3) PCL–hardystonite (HS) against SHAM as the control. Diffraction pattern from TEM showed that native HA and HS were polycrystalline and they leached higher ppm of calcium, phosphorus and zinc as compared to PCL–HA and PCL–HS in which HA, HS were incorporated in PCL nanofibers. The study was performed on 8 mm critical-sized rat calvarial defects analyzed at two timepoints, 6 and 12 weeks. The bone regenerated by PCL–HS promoted higher growth than that by SHAM and PCL alone at 12 weeks with comparable bone mineral density in all groups at both time points. PCL–HS showed potential for bone growth similar to that for PCL–HA. Histology data showed dense bone interface being formed at the site in both the PCL–HS and PCL–HA groups. Therefore, HS was found to have comparable functionality with commercial HA. No significant differences were noted in any of the blood parameters but there were differences in serum biochemistry parameters of triglyceride and creatine levels among groups, which are indirectly related to bone forming potential and directly to safety of kidney function, while the other parameters were unchanged and within the normal range. Thus, we conclude that the HS material can be a suitable substitute for bone tissue engineering.

Evaluation of safety and efficacy of Maa-Lact in lactating Holtzman rats

Abstract Objective To evaluate the safety & efficacy of Maa-Lact granules for its galactogougue activity in Holtzman rats and its effect on suckling pups. Methods Group I rats were treated as control, group II and III rats were treated with 500 mg/kg, 1 000 mg/kg of Maa-Lact granules for 21 days. Weekly body weights of dams and pups were collected, litter survivability for 22 days and ocular blood samples were collected on 1 st day of parturition and 21 st day of post parturition for the estimation of prolactin levels. On 21 st day blood samples were collected from retro-orbital sinus for haemotological and biochemical estimations. On the same day of weaning rats were sacrificed and subjected to necropsy and individual organ weights were recorded. Results No significant difference in weekly food weight consumption, body weights between control & treated groups with normal clinical signs. There is no mortaly in dams throught the study period with no significant difference in pups weights. The percentage mortality in pups was 14.43 %, 14.07 %, and 13.42% in group I, group II and group III, respectively. The histopathological finding has shown that treated groups have less convulution and adipose tissue deposition along with increase in length and branching of lactiferous duct and alveolar size. Conclusion Based on above results, it can be concluded that Maa-Lact posseses significant galctogogue activity.

PA01.16.Effect of sheetaprabha tablets on ethylene glycol induced urolithiasis in rats.

Purpose: Sheetaprabha tablets, Ayurvedic proprietary medicine, contain Sweta Parpati & Hajrul hahood bhasma as active ingredients. Sweta parpati is mainly indicated in mootravaha srotovikara & hajrul hahood bhasma is having mootrala and ashmari bhedana actions. A survey of the literature showed that no pharmacology study was made on the sweta parpati and sheetaprabha tablets. In the present study we investigated the effect of Sheetaprabha tablets in ethylene glycol induced urolithiasis in rats. Method: Urolithiasis was induced in male wistar rats by adding ethylene glycol (0.75%) in drinking water. Protective (130mg/kg & 260mg/kg) and curative effect (130mg/kg & 260mg/kg) of Sheetaprabha was studied in experimental animal models. Result: Ethylene glycol induced urolithiatic rats showed significant increase in blood urea nitrogen (P<0.001), creatinine & phosphorus (P<0.05) and also significant increase in SGOT, SGPT & ALP levels in serum, which were prevented by Sheetaprabha treated rats in protective groups and decreased in curative groups. Histopathologies of kidneys were prevented calcium oxalate formation and tubular degeneration, and increase in tubular regeneration was observed in protective (130mg/kg, 260mg/kg) group. Conclusion: The present study findings indicate that treatment with Sheetaprabha tablets, which decreases and also prevents the growth of the calcium oxalate crystals in urinary tract. It also seems that the preventive effect is more effective than its curative effect. Hence, this study confirms the traditional use of Sheetaprabha tablets in urolithiasis.