Preliminary studies on acute and subacute toxicity of an antidiabetic herbal preparation, Dianex.

Dianex, a polyherbal formulation intended to use for diabetic patients, has been screened for toxic effects. For acute toxicity studies, Dianex was administered orally in graded doses of 0.75-10 g/kg to the mice. For subacute toxicity studies, different doses of Dianex (1.0, 1.5 and 2.5 g/kg) were administered orally to the rats once daily for 30 days. Animals were observed for physiological and behavioural responses, mortality, food and water intake and body weight changes. Hematological evaluation was performed weekly. All the animals were sacrificed on 31st day and changes in organ weights and histology were examined. Biochemical studies were done in liver and serum. No mortality was observed up to 10 g/kg of Dianex in acute toxicity study. Daily administration of as high as 2.5 g/kg dose of Dianex did not result in any mortality or changes in gross behaviour, body weight, weight and histology of different organs or serum and liver biochemistry. However, significant increase in RBC count and hemoglobin level was observed in the treated animals at all doses. Other peripheral blood constituents were in the normal range. The dose of Dianex to produce significant antidiabetic activity in mouse, 0.25-0.5 g/kg, is much lower than the doses used in the present study. Therefore such doses may be safe for daily administration without causing any serious side effects.

Biodegradable microspheres of curcumin for treatment of inflammation.

Curcumin, a natural constituent of Curcuma longa (turmeric, CAS 458-37-7) was formulated as prolonged release biodegradable microspheres for treatment of inflammation. Natural biodegradable polymers, namely, bovine serum albumin and chitosan were used to encapsulate curcumin to form a depot forming drug delivery system. Microspheres were prepared by emulsion-solvent evaporation method coupled with chemical cross-linking of the natural polymers. Curcumin could be encapsulated into the biodegradable carriers upto an extent of 79.49 and 39.66% respectively with albumin and chitosan. Different drug:polymer ratios did not affect the mean particle size or particle size distribution significantly. However, the concentration of the crosslinking agent had remarkable influence on the drug release. In-vitro release studies indicated a biphasic drug release pattern, characterized by a typical burst-effect followed by a slow release which continued for several days. Evaluation of antinflammatory activity using Freund's adjuvant induced arthritic model in Wistar rats revealed significant difference between both the formulations, albumin microspheres and chitosan micropheres as well as against control. It was evident from the present study that the curcumin biodegradable microspheres could be successfully employed as prolonged release drug delivery system for better therapeutic management of inflammation as compared to oral or subcutaneous route.

The effect of indigenous Neem Azadirachta indica [correction of (Adirachta indica)] mouth wash on Streptococcus mutans and lactobacilli growth.

Neem is one of the most widely researched tropical tree, with almost all it's parts being put for a variety of uses. In the present study, the antibacterial effect of Neem mouthwash against salivary levels of streptococcus mutans and lactobacillus has been tested over a period of 2 months. Also it's effect in reversing incipient carious lesions was assessed. While streptococcus mutans was inhibited by Neem mouthwashes, with or without alcohol as well as chlorhexidine, lactobacillus growth was inhibited by chlorhexidine alone. The initial data appears to prove it's effect in inhibiting S. mutans and reversing incipient carious lesions, longer term clinical trials are essential.

Pharmacokinetic study of niosome encapsulated insulin.

Pharmacokinetic profile and hypoglycemic effect, after intraperitoneal injection of insulin and insulin encapsulated in niosomes were determined in diabetic rats. Niosomes (non-ionic surfactant vesicles) of different doses and different lipid compositions were prepared by lipid layer hydration method. Plasma samples were collected at specified time intervals and plasma concentration of insulin was determined by HPLC. Blood glucose level was estimated spectrophotometrically using commercial glucose assay kit. In vitro release and pharmacokinetic profile of niosomal formulation and free insulin were evaluated. Though there was a slight delay in the in vitro drug release due to cholesterol content in the niosomes, there was no difference between the two preparations when plasma levels were compared in vivo. Niosomes significantly reduced the blood glucose level in diabetic rats. Fall in blood glucose level was almost 92% of initial value. In case of the niosomal form the half-life of insulin was prolonged by 4 -5 hr in contrast to 2 hr for free drug. Niosomes maintained the plasma insulin level up to 12 hr, but free drug was cleared quickly. The area under the plasma concentration-time curve for niosomal forms was, 26.07 degrees +/- 0.99 mIU. hr/ml and for free insulin was 11.722 +/- 1.00 mIU. hr/ml. More than 80% of the drug was successfully encapsulated to give a formulation with sustained release characteristics. Entrapment efficiency increased with increasing lipid concentration and decreased with increasing drug concentration. The results showed that insulin entrapped in niosomes prolongs the existence of drug in the body therefore increasing its therapeutic value.

Prolonged release biodegradable vesicular carriers for rifampicin--formulation and kinetics of release.

An attempt has been made to design suitable liposome and niosome-encapsulated drug delivery system for rifampicin and evaluated the same in vitro and in vivo. A modified lipid layer hydration method was employed to prepare these vesicular carriers. The formulated systems were characterized in vitro for size distribution analysis, drug entrapment, drug release profiles and vesicular stability at different conditions of storage. In vivo drug kinetics was evaluated in normal, healthy albino rats for niosomal formulation upon subcutaneous injection and various pharmacokinetic parameters were determined. Niosomes and liposomes exhibited mean diameter of 9.73 and 11.87 microns with entrapment efficiencies of 30.5 and 34.2% respectively. Both the products exhibited sustained release characteristics in vitro with zero order drug release kinetics up to initial 10 hr. Stability evaluation indicated that both formulations were not significantly leaky over a period of one month. Niosomal formulation elevated plasma elimination half life and decreased elimination rate constants for rifampicin in vivo suggested that encapsulation retarded the removal of the drug from circulation compared to free drug due to slow drug release into systemic circulation. A five-fold increase in the area under plasma rifampicin concentration-time curve for niosomal rifampicin as compared to free drug indicated better bioavailability of encapsulated drug. It is evident from this study that niosomes and liposomes could be promising delivery systems for rifampicin with prolonged drug release profiles and reasonably good stability characteristics.

Development and evaluation of transdermal formulations containing metronidazole and norfloxacin for the treatment of burn wound.

In an attempt for better treatment of partial thickness burn wounds topical ointments containing metronidazole and norfloxacin in different bases were prepared and in vitro release was conducted in phosphate buffer pH 6. It was found that, diffusion of the metronidazole and norfloxacin from the lanolin petrolatum base with 0.25% w/w dimethyl sulfoxide was maximum through hairless rat abdominal skin. Antimicrobial activity of different prepared formulations was found to be more effective both against aerobic and anaerobic bacteria than marketed formulation (1% silver sulfadiazine cream USP). Formulations were significantly effective as compared to that of marketed formulation in wound contraction of the partial thickness burn wound. Histopathological reports supported effectiveness of formulations. It was found that 1% metronidazole and 1% norfloxacin ointments are suitable for treating the partial thickness burn wound.

Evaluation of anti-tumor efficacy of injectable Centchroman in mice bearing Ehrlich ascites carcinoma.

Anti-tumor efficacy of Centchroman formulated as niosomes and gel implant was evaluated in Swiss albino mice bearing Ehrlich ascites carcinoma at 10 mg/kg body weight dose given subcutaneously. Median day of death, percentage increase in host life span and changes in body weight were studied. Centchroman significantly (P < 0.05) increased the median day of death both in free and formulated systems. Also, injectable formulations exhibited a significant (P < 0.05) increase in host life span compared to free drug, hence, enhanced anti-tumor efficacy against Ehrlich ascites carcinoma.

Biodegradable dental implants of ciprofloxacin beta-cyclodextrin inclusion complex in the treatment of periodontitis.

Dental implants of ciprofloxacin beta-cyclodextrin inclusion complex were formulated using poly (epsilon-caprolactone), a biodegradable polymer and evaluated. Clinical evaluation was carried out in ten patients with acute peridontitis. Various clinical parameters, viz. gingival index, plaque score, attachment gain, reduction in pocket depth were evaluated at 10, 20, 30, 40 days of treatment and compared with placebo as control. A significant (P < 0.0001) improvement in the healing of periodontal pockets treated with ciprofloxacin beta-cyclodextrin implant was observed in most of the clinical parameters. Estimation of gingival crevicular fluids (GCF) for the drug content revealed that drug levels above the minimum inhibitory concentration (10.2 micrograms/mg) for many of the periodontal pathogens were maintained throughout the period of study (40 days). This confirms the clinical efficacy of the dose and the duration of the study. It was found that biodegradable carrier was better accepted than the non-biodegradable carriers reported earlier.

Reduced toxicity and enhanced antitumor efficacy of betacyclodextrin plumbagin inclusion complex in mice bearing Ehrlich ascites carcinoma.

Inclusion complex of plumbagin was prepared with betacyclodextrin employing neutralization method. The toxicity of the drug was reduced and the antitumor efficacy was enhanced on complexation with betacyclodextrin.

Antitumor and antifertility activities of plumbagin controlled release formulations.

With a view to increase efficiency and reduce toxicity of Plumbagin, an attempt was made to formulate plumbagin as a controlled release preparation using various carriers and test for their antitumor and antifertility activities. Niosomes and albumin microspheres were used as carriers. In vitro data showed promising results for these formulations thus they were taken up for in vivo assessment. Given at a dose of 5 mg/kg, ip the albumin microspheres showed promising antitumor and antifertility activity when compared to the niosomes on control. Animal survival data also indicated slight improvement in survival rate and thus antitumoral activity. Also, an interesting point was that the antifertility activity was affected through an antiovulatory action as seen from histopathological studies.

Toxicity and antitumor activity of niosomal bleomycin in tumor bearing mice.

Niosomal encapsulation of bleomycin enhanced the antitumor activity against Ehrilich ascites and sarcoma-180 models. The niosomal/free drug mean survival time values of 1.28 was achieved in Ehrlich ascites infected animals. Niosomal bleomycin considerably increased the 40 days survival rate in mice. Tumor volume doubling time of S-180 tumor was also increased significantly in niosomal treated animals. Histopathological studies of lung and jejunum of Niosomal bleomycin treated mice, confirmed the less toxic potential of encapsulated bleomycin. The suppression of peripheral and bone marrow WBC counts upon niosomal bleomycin treatment was not substantial.

Altered biological distribution and decreased neuromuscular toxicity of niosome encapsulated vincristine.

Effects of encapsulation within niosomes (nonionic surfactant vesicles) on the biological distribution and toxicity of vincristine-a widely used anticancer drug have been investigated. Plasma kinetics, tissue distribution profile and neuromuscular toxicity of niosomal vincristine (NVCR) were compared with those of free vincristine (FVCR). NVCR was cleared from the plasma much more slowly [t1/2(beta) = 1.388 hr] than FVCR [t1/2(beta) = 0.74 hr]. Over the 48 hr period of experiment, the niosome formulation delivered significantly more drug to the plasma compartment than FVCR and resulted in reduced accumulation of drug in gut and skeletal muscle. Encapsulation caused a marked alteration in the tissue disposition of the drug. NVCR was less toxic both in terms of mortality and morbidity. Importantly, histopathological studies of skeletal muscle, spinal cord and sciatic nerve of NVCR treated albino wistar rats demonstrated the less toxic potential of encapsulated vincristine. Further, the biochemical studies, estimation of enzymes plasma creatine phosphokinase and lactate dehydrogenase, confirmed the safety profile of NVCR. The decreased partitioning of NVCR to non active sites resulted in a significant amelioration of the toxic side effects, gastrointestinal and myological in particular, of the drug. The results indicate that the delivery of vincristine by encapsulating it in niosomes offer an efficient means of decreasing its toxic effects.

Antibacterial activity of ciprofloxacin-beta-cyclodextrin complex and its efficacy in dental implants.

Ciprofloxacin forms an inclusion complex with beta-cyclodextrin. The in vitro antibacterial activity of ciprofloxacin on E. coli and Staphylococcus aureus was found better on complexation. The complex was found very effective as a local antibacterial agent when used in dental implants. Significant reduction in the gingival index, probing pocket depth and microbial growth coupled with gain in attachment at the test site compared to control on the 14th day was observed when the implants containing 2.0 mg of the complex equivalent to 0.4 mg of ciprofloxacin was used in clinical trials.

Formulation and evaluation of controlled release dental implants of povidone iodine for periodontitis.

Diseases of the periodontium continue to be one of the man's most wide spread afflictions. Periodontitis is one of such which is characterised by a periodontal pocket formed due to the inflammatory disease of gingiva and the deeper periodontal tissues. Local controlled release implants of povidone iodine was prepared using various polymers and stability, release characteristics, total drug content etc, were evaluated. The clinical studies of the dental implants were carried out on 10 patients.