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Biomedical subjects

N Udupa

Publications and source records attributed to N Udupa.

At least 19 recordsLinked to original sources
PubMed2006

In Vitro and In Vivo preparation evaluations of bleomycin implants and microspheres Prepared with DL-poly (lactide-co-glycolide).

In this investigation, poly(lactide-co-glycolide) (PLGA) gel implants and microspheric depot systems of bleomycin (BLM) were formulated and evaluated in vivo in mice bearing transplantable solid tumor (fibrosarcoma). The pharmacodynamic studies showed that both the formulations retarded tumor growth significantly (p<0.05) when compared to the control animals (without any drug treatment). Preliminary pharmacokinetic studies illustrated controlled release of the drug into the systemic circulation to elicit the anti-neoplastic action. The gel implants showed better release characteristics and greater pharmacodynamic action when compared to the microspheres, thus demonstrating the feasibility of employing biodegradable depot polymer gel matrix for chronic cancer therapy.

Animals↗
PubMed2005

Effect of Dianex, a herbal formulation on experimentally induced diabetes mellitus.

Dianex, a polyherbal formulation consisting of the aqueous extracts of Gymnema sylvestre, Eugenia jambolana, Momordica charantia Azadirachta indica, Cassia auriculata, Aegle marmelose, Withania somnifera and Curcuma longa was screened for hypoglycemic activity in normal and streptozotocin induced diabetic mice. Dianex was administered in different doses of 100-500 mg/kg/day orally in acute (6 h) and long-term (6 weeks) studies. Blood glucose levels were checked 2-6 h after treatment in acute studies and every 2 weeks in long-term studies. Body weight was recorded on the first and final day of the treatment in the long-term studies with diabetic mice. After 6 weeks, high-density lipoprotein, triglycerides, total cholesterol, alanine transaminase (ALT), aspertate transaminase (AST), urea and creatinine were estimated in serum of the diabetic mice. Glycogen and total protein levels were estimated in the liver. Also, the liver and pancreas was subjected to histological examination. Oral glucose tolerance and in vitro free radical scavenging activity was also studied. Dianex produced significant (p<0.05) hypoglycemic activity at 250-500 mg/kg doses in both normal and diabetic mice in acute and long-term studies. The body weight of diabetic mice significantly (p<0.05) increased with all tested doses of Dianex. The elevated triglycerides, cholesterol, ALT, AST, urea and creatinine levels in diabetic mice were significantly (p<0.05) reduced at the doses of 250 and 500 mg/kg. The liver glycogen and protein levels were both significantly (p<0.05) increased in diabetic mice at 250 and 500 mg/kg doses. Dianex increased the glucose tolerance significantly (p<0.05) in both normal and diabetic mice at all the doses tested. Histopathological examination showed that the formulation decreased streptozotocin induced injury to the tissues at all the doses tested. It produced significant (p<0.05) free radical scavenging activity against ABTS+, DPPH and hydroxyl free radicals at the concentrations ranging between 10-1000 microg/ml.Thus, in the present study, Dianex produced significant hypoglycemic activity in both normal and diabetic animals. It also reversed other diabetic complications in diabetic mice at 250 and 500 mg/kg doses. In our earlier study, Dianex was well tolerated in laboratory animals at higher doses (upto 10 g/kg in mice, acute toxicity; up to 2.5 g/kg in rats, subacute toxicity studies for 30 days) without exhibiting any toxic manifestation. Hence, Dianex may be useful in the treatment of diabetes mellitus.

Administration, Oral↗
PubMed2004

Glibenclamide transdermal patches: physicochemical, pharmacodynamic, and pharmacokinetic evaluations.

In the present study, matrix type transdermal patches containing glibenclamide were prepared using different ratios of ethyl cellulose (EC)/polyvinylpyrrolidone (PVP) and Eudragit RL-100 (ERL)/Eudragit RS-100 (ERS) by solvent evaporation technique. The possible drug and polymer interaction was studied by infrared spectroscopy, differential scanning calorimetry, and HPTLC analysis. All the prepared formulations were subjected to physicochemical studies (thickness, weight variation, drug content, moisture content and uptake, and flatness), in vitro release and in vitro permeation studies through mouse skin. The results suggested that there was no interaction between drug and polymers. Variations in drug release/permeation profiles among the formulations studied were observed. The microphotographs obtained by scanning electron microscopy showed the formation of pores on the surface of the patches after in vitro skin permeation studies. Based on physicochemical and in vitro skin permeation studies, the formulations with EC:PVP (3:2) and ERL:ERS (4:1) were selected for in vivo experiments. The hypoglycemic activity of the patches in comparison with oral glibenclamide administration was studied for acute (24 h) and long-term (6 weeks) effect in both normal and streptozotocin-induced diabetic mice. Various biochemical parameters (serum levels of high-density lipoprotein-cholesterol, triglycerides, total cholesterol, alanine transaminase, aspertate transaminase, urea, and creatinine and liver protein and glycogen content) and histopathological (liver, pancreas and stomach) studies were carried out in diabetic mice after treating for 6 weeks. The patches were subjected to skin irritation test (by both visual observation and histopathological evaluation), oral glucose tolerance test and pharmacokinetic evaluation in mice. The results revealed that the patches successfully prevented the severe hypoglycemia in the initial hours, which is the major side effect associated with oral route. The patches maintained similar effect during long-term treatment also. The transdermal systems produced better improvement with all the tested biochemical parameters compared to oral administration. They produced improved repair of the tissues after diabetes induced tissue injury and exhibited negligible skin irritation. The pharmacokinetic evaluation showed that the patches could maintain almost steady-state concentration of drug within the pharmacologically effective range for prolonged period of time. The better in vivo performance of the transdermal patches of glibenclamide in comparison with oral administration could be due to day-to-day glycemic control on long-term application.

Administration, Cutaneous↗
PubMed2004

Evaluation of antiplaque activity of Azadirachta indica leaf extract gel--a 6-week clinical study.

Various chemical agents have been evaluated over the years with respect to their antimicrobial effects in the oral cavity; however, all are associated with side effects that prohibit regular long-term use. Therefore, the effectiveness of neem (Azadirachta indica A. Juss) leaf extract against plaque formation was assessed in males between the age group of 20-30 years over a period of 6 weeks. Present study includes formulation of mucoadhesive dental gel containing Azadirachta indica leaf extract (25 mg/g). A 6-week clinical study was conducted to evaluate the efficacy of neem extract dental gel with commercially available chlorhexidine gluconate (0.2% w/v) mouthwash as positive control. Microbial evaluation of Streptococcus mutans and Lactobacilli species was carried out to determine the total decrease in the salivary bacterial count over a period of treatment using a semi-quantitative four quadrant streaking method. The results of the study suggested that the dental gel containing neem extract has significantly (P<0.05) reduced the plaque index and bacterial count than that of the control group.

Adult↗
PubMed2004

The effect of two different dental gels and a mouthwash on plaque and gingival scores: a six-week clinical study.

AIM: To evaluate the clinical efficacy of two gel formulations containing chlorhexidine gluconate and neem extract with a commercially available chlorhexidine gluconate mouthwash. METHOD: An open labelled randomised six-week clinical study with parallel group design in 48 subjects divided into four groups. Plaque accumulation and gingival condition were recorded using plaque index and gingival index. On the basis of mean baseline plaque and gingival scores, subjects were allocated to four different groups, using their assigned products twice a day, before bed and after breakfast. Plaque and gingival scores were recorded after three and six weeks. RESULTS: Mean plaque and gingival scores were reduced over the six-week trial period for experimental and control groups. Chlorhexidine gluconate gel reduced the plaque and gingival scores significantly more (p<0.05) than the chlorhexidine gluconate mouthwash. Neem extract gel also showed significant (p<0,05) reduction in plaque and gingival scores when compared with the control group. But there was no significant difference between the groups treated with chlorhexidine gel and neem extract gel. CONCLUSION: The results of this clinical study indicate that better therapeutic efficacy can be achieved using gels for treating oral infections than conventional treatments using mouthwash.

Adult↗
PubMed2003

Investigation into the potential of iontophoresis facilitated delivery of ketorolac.

The potential for iontophoresis facilitated transdermal transport of ketorolac was investigated using rat skin. Studies of electrical, physicochemical and device-related factors acting on the permeation kinetics of in vitro iontophoresis were performed. Iontophoresis increased the transdermal permeation flux of ketorolac as compared to the diffusion. Increase in applied current density or decrease in ionic strength of the donor solution enhanced the flux of the drug. Use of either platinum or silver/silver chloride electrodes resulted in similar enhancement of drug flux. Continuous current was more potent than pulsed current in promoting ketorolac transdermal permeation. Increasing the frequency or on:off ratio of pulse current induced an enhancement of the flux through the skin. An increase in donor drug loading dose or increasing the duration of current application resulted in enhancement of the drug flux. Pretreatment of the skin with D-limonene in ethanol or D-limonene in ethanol + ultrasound significantly enhanced the iontophoretic flux of the drug in comparison to passive flux with or without pretreatment. Trimodality treatment comprising of pretreatment with D-limonene in ethanol + ultrasound in combination followed by iontophoresis was found to be most potent for enhancing the rate of permeation of ketorolac.

Adjuvants, Pharmaceutic↗
PubMed2003

Potential applications of polymeric microsphere suspension as subcutaneous depot for insulin.

The objective of this investigation was to develop an injectable, depot-forming drug delivery system for insulin based on microparticle technology to maintain constant plasma drug concentrations over prolonged period of time for the effective control blood sugar levels. Formulations were optimized with two well-characterized biodegradable polymers namely, poly(DL-lactide-co-glycolide) and poly-epsilon-caprolactone and evaluated in vitro for physicochemical characteristics, drug release in phosphate buffered saline (pH 7.4), and evaluated in vivo in streptozotocin-induced hypoglycemic rats. With a large volume of internal aqueous phase during w/o/w double emulsion solvent evaporation process and high molecular weight of the polymers used, we could not achieve high drug capture and precise control over subsequent release within the study period of 60 days. However, this investigation revealed that upon subcutaneous injection, the biodegradable depot-forming polymeric microspheres controlled the drug release and plasma sugar levels more efficiently than plain insulin injection. Preliminary pharmacokinetic evaluation exhibited steady plasma insulin concentration during the study period. These formulations, with their reduced frequency of administration and better control over drug disposition, may provide an economic benefit to the user compared with products currently available for diabetes control.

Animals↗
PubMed2003

A toxicological evaluation of 2-dimethylaminomethyl-1-phenyl-2-propen-1-one hydrochloride.

2-Dimethylaminomethyl-1-phenyl-2-propen-1-one hydrochloride (3) is a novel cytotoxic and anticancer agent. The objective of this study was to obtain information pertaining to possible toxic symptoms detected by in vivo evaluations in mice and an in vitro test for mutagenicity. The data obtained revealed that 3 had no effect on alanine transaminase, aspartate transaminase, HDL cholesterol and protein concentrations in sera nor were variations in the numbers of red and white blood cells detected. Furthermore autopsies of treated mice revealed no pathological symptoms in the heart, kidney, brain, spleen and testes. However elevation of the concentrations of total cholesterol, triglycerides, creatinine and urea were noted in treated mice as well as inflammation of the liver and lungs. Chromosomal aberrations were detected in a micronuclei test. In the Ames test, compound 3 was converted into one or more mutagens in the presence (but not the absence) of a murine liver homogenate. Thus future molecular modifications of 3 should bear in mind approaches to reduce or minimize unwanted side effects.

Animals↗
PubMed2003

Effect of some penetration enhancers on the permeation of glibenclamide and glipizide through mouse skin.

The purpose of this investigation was to study the effect of some penetration enhancers on in vitro permeation of glibenclamide and glipizide through mouse skin. Ethanol in various concentrations, N-methyl-2-pyrrolidinone, transcutol, propylene glycol and terpenes like citral, geraniol and eugenol were used as penetration enhancers. The in vitro skin permeation experiments were conducted by both simultaneous application of drug and enhancer solution and by pretreatment of the skin with neat enhancer. At the end of the experiment drug retained in the skin was estimated. The flux values (microg/cm2/h) of both drugs significantly (p < 0.05) increased in the presence of penetration enhancers, except transcutol and propylene glycol. The glibenclamide flux values ranged from 1.42 +/- 0.09 without enhancer, to 18.25 +/- 1.21 in a combination of 50% ethanol and 5% eugenol. Glipizide flux values ranged from 3.21 +/- 0.51 without enhancer, to 57.21 +/- 5.25 in a combination of 50% ethanol and 5% eugenol. Skin retention and solubility of both drugs increased with all penetration enhancers compared to control (except propylene glycol). As the target permeation rates for glibenclamide and glipizide were calculated to be 193.8 and 184.8 microg/h respectively, the present study showed that the required permeation rates for both drugs could be achieved with the aid of enhancers by increasing the area of application in an appreciable range.

Animals↗
PubMed2003

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.

Administration, Oral↗
PubMed2002

Temperature sensitive liposomes of plumbagin: characterization and in vivo evaluation in mice bearing melanoma B16F1.

The effectiveness of the combination of thermosensitive liposomes of plumbagin and hyperthermia is described. Small-sized, thermosensitive liposomes were prepared by thin film hydration and subsequent sonication. The liposomes were characterized for size, phase transition temperature, in vitro drug release and stability. The results of particle size analysis indicated that almost 90% of the vesicles were below 0.19 microm size. The phase transition temperature of the liposomes as determined by differential scanning calorimetry was found to be 41.32 degrees C. The results of in vitro release studies in phosphate buffered saline + mouse plasma indicated that maximum drug release (51.25%) occurred at 42 degrees C compared to the less than 9% release at 37 degrees C. Better stability profile was observed when the plumbagin liposomes were stored at 4 degrees C. When combined with localised hyperthermia (43 degrees C, 30 min or 1 h), liposomal plumbagin administered intravenously to C57BL/6J mice bearing melanoma exhibited better anticancer activity as compared to animals treated with an equivalent dose of free plumbagin with or without hyperthermia, which was evident by enhanced volume doubling time and growth delay.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2002

Optimization and performance evaluation of peptide-loaded monolithic poly-epsilon-caprolactone microspheres in mice bearing melanoma B16F1.

The objective of this investigation was to develop a bleomycin depot based on monolithic microparticulate technology to suppress tumour growth and to maintain constant plasma drug concentrations within an optimal therapeutic window over a prolonged period of time. Formulations were optimized with biodegradable poly-epsilon-carpolactone and evaluated in vitro for physicochemical characteristics, drug release in phosphate buffered saline (pH 7.4) and evaluated in vivo in tumour bearing mice. This investigation revealed that upon subcutaneous injection, the biodegradable depot-forming poly-epsilon-carpolactone microspheres controlled drug release and suppressed tumour growth kinetics significantly compared to control. A preliminary pharmacokinetic evaluation exhibited steady plasma drug concentrations during the study period. This formulation with its reduced frequency of administration and better control of drug disposition is expected to provide an economic benefit to the user compared with products currently available for chemotherapy.

Animals↗
PubMed2002

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.

Absorbable Implants↗
PubMed2002

Transdermal delivery of glibenclamide and glipizide: in vitro permeation studies through mouse skin.

The purpose of this investigation was to study the feasibility of transdermal delivery of glibenclamide and glipizide. In vitro permeation of these drugs was studied through mouse skin using various penetration enhancers like Tween -20, polyethyleneglycol-400, ethanol and d-limonene by simultaneous application of drug and enhancer solution or by pretreatment of the skin with neat enhancer. The partition coefficient values indicated that both drugs partition well into the skin. Glipizide did not show any skin metabolism, while glibenclamide showed a minimal metabolism during in vitro skin metabolism studies. The flux values (microgram/cm2/h) of both drugs significantly (p < 0.05) increased in the presence of penetration enhancers. The glibenclamide flux values ranged from 1.39 +/- 0.13 without enhancer, to 19.01 +/- 2.14 in a combination of 50% ethanol and 5% d-limonene. Glipizide flux values ranged from 3.01 +/- 0.74 without enhancer, to 62.97 +/- 7.10 in a combination of 50% ethanol and 5% d-limonene. Skin retention and solubility of both drugs increased with all penetration enhancers compared to control. The target permeation rates for glibenclamide and glipizide were calculated to be 193.8 and 184.8 micrograms/h respectively. The present study showed that the target permeation rates for both drugs could be achieved with the aid of enhancers by increasing the area of application in an appreciable range.

Administration, Cutaneous↗
PubMed2000

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.

Animals↗
PubMed2000

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.

Animals↗