Delivery of drugs into systemic circulation via skin has generated lot of interest during the last decade. Transdermal drug delivery systems (TDDS) offer many advantages over the conventional dosage forms or controlled release peroral delivery systems. TDDS provides; constant blood levels (l-7 days), avoids first-pass metabolism, increased patient compliance, and dose dumping never occurs. The choice of drugs delivered transdermally, clinical needs, and drug pharmacokinetics are some of the important considerations in the development of TDDS. In addition to methods to enhance transdermal absorption of drugs such as sorption promoters and prodrugs, the physicochemical and biological factors affecting transdermal permeation of drugs are discussed. Although, novel approaches like ion-tophoresis and ultrasound are gaining importance as a means to increase drug permeation into systemic circulation, clinical products based on these approaches are still far away. The importance of appropriate animal model selection in the development and evaluation of TDDS cannot be ignored. The cost per milligram of drug delivered transdermally is more expensive than peroral route. The added cost could be justified, if TDDS improve patient compliance and reduces toxic/side effects.

Objective: To study the effect of copper benzohydroxamic acid complex (CU-BHA) against Ehrlich ascites carcinoma (EAC) in Swiss A mice. Methods: CU-BHA complex was synthesized from benzohydroxamic acid and CuSO4 solution. Swiss A mice inoculated with EAC cells were treated with the Cu-BHA complex and their longivity was compared with the untreated control group. Different biochemical parameters (alkaline phosphatase activity and lipid peroxidation in serum) and haematological parameters were noted. Transplantability of CU-BHA complex treated EAC cells were observed. Results: CU-BHA complex (25 mg./kg) enhanced longivity of tumour bearing mice significantly. Transplantability of EAC cells were reduced by Cu-BHA treatment. Haematological parameters and serum alkaline phosphatase activity in tumour bearing mice were found to be significantly altered but, Cu-BHA treatment recovered those parameters towards normal values. Conclusion: The CU-BHA complex was found to be a potential antitumour drug. The tumour bearing mice treated with this complex showed negligible host-toxicity.

Objective: To study the effects of neem kernel powder(NP) and glibenclamide. alone or in combination, on alloxan diabetic rats. Methods: The diabetic rabbits were given with NP alone or in combination with glibenclamide for thirty days and at the end of thirty days the serum lipid levels, blood glucose and activities of some serum, liver and intestinal enzymes were assessed. Results: Administration of NP alone (500 mg/kg) as well as the combination of NP (250mg/kg) with glibenclamide (0.25mg/kg) significantly decreased the concentration of serum lipids, blood glucose and activities of serum enzymes like alkaline phosphatase (alk P), acid phosphatase (acid P), lactate dehydrogenase (LDH), liver glucose 6-phosphatase (G6P) and HMG CoA reductase activity in liver and intestine of alloxan diabetic rabbits. However, all the treatments produced an increased liver hexokinase activity. The changes observed were significantly greater when the treatment was given in combination of NP and glibenclamide than with NP alone. Conclusion: Our data suggest a significant antidiabetic and antihyperlipaemic effect of NP in alloxan diabetic rabbits.

Objective: To prepare poly (lactic-co-glycolic) acid (PLGA) injectable gel implant for the delivery of plumbagin (PLB) to reduce the toxicity and enhance the antitumour efficacy. Method: PLGA was dissolved in triacetin and PLB was dissolved in this. A gel matrix was formed immediately on contact with aqueous fluid. In vitro release studies were carried out in phosphate buffered saline pH 7.4. Acute toxicity studies were performed in normal BALB/c mice and antitumour efficacy in BALB/c mice bearing Sarcoma-180 tumour. LD50 and volume doubling time (VDT) values for plain PLB and gel implant injection was found after subcutaneous injection. Results: In vitro release of PLB was observed for a week. It was dependent on the concentration of PLGA used. The LD50 for plain PLB and gel Implant was found to be 8.60 mg/kg and 9.33 mg/kg. VDT for plain PLB and gel implant was found to be 6.5ñ 0.9 days and 11.5 ñ 0.5 days respectively. Conclusion: The toxicity of PLB was reduced in mice after subcutaneous injection of the gel containing PLB compared to plain PLB. The VDT was significantly higher for the gel compared to plain PLB. Thus the gel implant could be an effective drug delivery system for reducing toxicity and enhancing the therapeutic efficacy of PLB.

Objective: To evaluate the antiinflammatory-analgesic property of the 4',5,6-trihydroxy-3',7-dimethoxy-flavone from Vicoa indica DC using different agents and models. Methods: Antiinflammatory effects were produced by different inflammatory agents and after 4 hours the hind paw of the animals were sacrified and weighed in a torsion balance. Analgesic effects were assessed by using different models and by acetic acid. In the former the analgesic effect was noted for a stipulated period of time and in the latter the writhings was counted for 15 minutes. Results: The drug 4', 5, 6-trihydroxy-3',7-dimethoxyflavone at 50 mg/kg body weight was very effective in producing inhibition in both antiinflammatory-analgesic models. Conclusion: This drug recorded consistent inhibitory and antiodema effects in the different agents used for the study.

Objective: To study the effects of furosemide on the isolated guinea pig tracheal spirals in the presence of compound 48/80 and antigen (egg albumin). Methods: Compound 48/80 and egg albumin were used to produce contractions of the non-sensitised and sensitised guinea pig trachea respectively. Furosemide was added in the bath 15 min prior to compound 48/80 or egg albumin challenge. In a separate set of experiments, the effects of furosemide were tested in the presence of indomethacin. Contractions were recorded for a period of 60 min. Results: Furosemide at concentrations of 10-6M and 10-5M significantly attenuated the tracheal contractions induced by compound 48/80 and egg albumin and altered the time duration and the area under the time-contraction curve. The inhibitory effect of furosemide was partially reversed by the preincubation of the tissue with indomethacin (8.6 x 10-6M). Conclusion: The studies reveal that furosemide may be causing a local release of PGE2 into the airways or could be affecting mediator release from mast cells and may thus be contributing to the observed effect.

Objective: To study sound stress-induced changes and their modification by drugs in albino rats. Methods: Sound stress of 100 dB ñ 5 for 30 min was produced by electric bells. Serum glutamate oxaloacetate transaminase (SGOT), Serum glutamate pyruvate transaminase (SGPT), Serum cholesterol levels, serum triglycerides and blood glucose levels were estimated using Miles India Ltd. Kits. His-topathological studies of adrenalskidneys and myocardium were also undertaken. Results: Sound stress caused significant increase in SGOT, SGPT and serum cholesterol levels and significant reduction in serum triglyceride level. Pretreatment with diazepam (DZ)/propranolol (Prop) modified biochemical, enzymological and histological changes in animals exposed to sound stress. Conclusion: The protective/preventive effect of DZ/Prop in this experiment is attributed to their ability to inhibit stress-induced activation of HPA-axis and sympathetic stimulation and functional alteration of cell membranes due to steroidal storm.

Objective: To study the effect of centrally administered adenosine, ATP and caffeine on Brewer's yeast-induced peripheral inflammation and nociception in rats Methods: ICV cannulation was performed in rats. ATP (50 'g), adenosine (50 'g) and caffeine (20 'g) were administered centrally, 30 min before administration of phlogistic agent. Acute inflammation was induced by administration of Brewer's yeast suspension below the plantar aponeurosis of hind paw of rats. The hind paw oedema volume and pain threshold were measured by plethysmometer and analgesiometer respectively. Results: ATP showed significant inhibition of Brewer's yeast-induced pedal oedema with concomitant reduction of protein content of exudate. However, adenosine, in addition attenuated pain. Caffeine did not alter the oedema volume, protein content of the exudate or pain threshold. Conclusion: The present study suggests that central purinergic system exerts anti-inflammatory effect and confirms the involvement of CNS in modulating peripheral inflammation.

Objectives: The present study was designed to investigate whether pentazocine protects against electrically-Induced seizures in mice. An attempt was also made to determine the possible opioid receptor mechanism involved. Methods: Maximal electroshock (MES) seizures were induced in mice via transauricular electrodes (60 mA, 0.2 sec). Seizure severity was assessed by the duration of hindlimb extensor phase. Results: lntraperitoneal administration of pentazocine resulted in a dose dependent inhibition of the hind-limb extensor phase during the MES. The ED50for the effect was found to be 15 mg/kg. The anticonvulsant effect of pentazocine was completely antagonized by the high doses (1.O mg/kg, 5.0/kg), but not by the low doses (0.1 mg/kg, 0.25mg/kg) of i.p. naloxone. Conclusion: The results suggest that the anti-MES effect of pentazocine is mediated by k-receptors, since naloxone in high doses is known to block these receptors.

Objective: The present study was designed to evaluate the effect of Ginkgo biloba (a PAF antagonist) on chemoshock in mice. Methods: Picrotoxin and strychnine were used for inducing chemoconvulsions in mice. The onset, duration, nature, severity of convulsions and mortality were observed. The severity of convulsions was assessed by scoring method. Results: Picrotoxin and strychnine produced convulsions in higher doses but not in lower doses. Prior administration of G. biloba extract potentiated the action of picrotoxin and strychnine respectively. Conclusion: The potentiation of picrotoxin action by G. biloba indicates the involvement of GABAergic system and chloride channel. Facilitation of strychnine action by G. biloba indicates the modulating effect of the extract on glycine.

Objective: To assess fear potentiated poststartle activity in adult rats administered clomipramine during neonatal period (" CLI rats"). Methods: Rat pups were treated twice daily from postnatal day 5 to 21 with clomipramine (15 mg/kg, SC). At three months of age CLI rats were given twenty trials per day, for two days. In each trial an unconditioned stimulus (US), namely footshock (0.8 mA) was presented during the last 0.5 sec of the 1 .O sec conditioned stimulus (CS), namely light. Twenty-four hours after the last conditioning trial, rats were presented with twenty alternated sequence of light-tone (98 dB) and tone-alone trials. Results: CLI rats showed an enhanced potentiated poststartle activity and increased activity in open field as compared to control rats. Conclusion: The present data suggest an increased expression of fear/anxiety in CLI rats,

Objective: To study the effect of copper benzohydroxamic acid complex (CU-BHA) against Ehrlich ascites carcinoma (EAC) in Swiss A mice. Methods: CU-BHA complex was synthesized from benzohydroxamic acid and CuSO4 solution. Swiss A mice inoculated with EAC cells were treated with the Cu-BHA complex and their longivity was compared with the untreated control group. Different biochemical parameters (alkaline phosphatase activity and lipid peroxidation in serum) and haematological parameters were noted. Transplantability of CU-BHA complex treated EAC cells were observed. Results: CU-BHA complex (25 mg./kg) enhanced longivity of tumour bearing mice significantly. Transplantability of EAC cells were reduced by Cu-BHA treatment. Haematological parameters and serum alkaline phosphatase activity in tumour bearing mice were found to be significantly altered but, Cu-BHA treatment recovered those parameters towards normal values. Conclusion: The CU-BHA complex was found to be a potential antitumour drug. The tumour bearing mice treated with this complex showed negligible host-toxicity.