Biomedical subjects

N K Jain

Publications and source records attributed to N K Jain.

At least 19 recordsLinked to original sources

PubMed2007

Elastic liposomes mediated transdermal delivery of an anti-hypertensive agent: propranolol hydrochloride.

One major problem encountered in transdermal drug delivery is the low permeability of drugs through the skin barrier. In the present investigation ultradeformable lipid vesicles, that is, elastic liposomes were prepared incorporating propranolol hydrochloride for enhanced transdermal delivery. Elastic liposomes bearing propranolol hydrochloride were prepared by conventional rotary evaporation method and characterized for various parameters including vesicles shape and surface morphology, size and size distribution, entrapment efficiency, elasticity, turbidity, and in vitro drug release. In vitro flux, enhancement ratio (ER), and release pattern of propranolol hydrochloride were calculated for transdermal delivery. In vivo study conducted on male albino rats (Sprague Dawley) was also taken as a measure of performance of elastic liposomal, liposomal, and plain drug solution. The better permeation through the skin was confirmed by confocal laser scanning microscopy (CLSM). Results indicate that the elastic liposomal formulation for transdermal delivery of propranolol hydrochloride provides better transdermal flux, higher entrapment efficiency, ability as a self-penetration enhancer and effectiveness for transdermal delivery as compared to liposomes.

Administration, Cutaneous↗

PubMed2006

Elastic liposomes mediated transcutaneous immunization against Hepatitis B.

Transcutaneous immunization presents a major challenge due to poor permeability of antigens through the skin barrier. To overcome this limitation ultradeformable lipid vesicles, the elastic liposomes, could be a better module for transcutaneous delivery of these proteinaceous antigens. In the present investigation Hepatitis B surface antigen (HBsAg)-loaded elastic liposomes were utilized as a mode for enhanced immunity against the antigen. Elastic liposomes were prepared by conventional rotary evaporation method and characterized for various parameters such as vesicles shape and surface morphology, size and size distribution, entrapment efficiency, elasticity, turbidity, stability and in vitro release pattern. Ex vivo cellular uptake and fluorescence studies were also conducted. In vivo studies were performed by measuring the immune response elicited by topically applied HBsAg-loaded elastic liposomes and compared to the intramuscularly administered alum-adsorbed HBsAg solution, topically applied plain HBsAg solution and physical mixture of HBsAg and elastic liposomes. Results indicate that transcutaneous immunization via elastic liposomes induces robust systemic and mucosal antibody response against HBsAg as compared to other formulations. The fluorescence microscopy results suggest prominent skin permeation and biodistribution, demonstrating efficient delivery of antigens to the immunocompetent Langerhans cells (LC) and lymphatics. The elastic liposomal formulation provides higher entrapment efficiency, enhanced penetration and effective immunoadjuvant property justifying its potential for improved vaccine delivery.

Administration, Cutaneous↗

PubMed2006

PEGylated peptide dendrimeric carriers for the delivery of antimalarial drug chloroquine phosphate.

PURPOSE: The present study was aimed at developing and exploring the use of uncoated and chondroitin sulfate A (CSA) coated PEGylated poly-L-lysine-based dendrimers for controlled and sustained delivery of a blood schizonticide, chloroquine phosphate (CQ). METHODS: The poly-L-lysine-based peptide dendrimers with PEG amine core prepared and coated with CSA were used to encapsulate the drug molecules by dialysis method. Effect of CSA coating on the surface characteristics, drug entrapment, drug release, stability, hemolytic toxicity, macrophageal interactions, and cytoadherence were determined and compared with those of uncoated systems. RESULTS: The CSA coating of the carriers was found to increase size and drug loading capacity, and reduce drug release rate and hemolytic toxicity. Transmission electron microscopic study revealed the surface properties of the systems. Stability studies had shown increased stability of the formulations on CSA coating. There was a significant reduction in hemolytic toxicity and cytotoxicity of CQ by the present dendrimeric carriers, which became more prominent on further CSA conjugation of the equivalent drug-loaded dendrimeric carriers. There were also significant reduction in levels of ring and trophozoite stages of Plasmodium falciparum in liquid culture when treated with CSA coated dendrimers because of the expression of similar carbohydrate receptors as that by placental and cerebral barriers for infected red blood cells. The systems were also found suitable for prolonging and controlling the blood level of drug as indicated by blood level and organ distribution studies in albino rats on intravenous administration, precluding any significant hematological or toxicological manifestations. CONCLUSION: Thus it can be said that CSA coating can improve drug-loading capacity, control and sustain the release of CQ from such carriers, and can suitably act as safer and effective carriers for intravenous CQ administration.

Animals↗

PubMed2006

Dendrimers: novel polymeric nanoarchitectures for solubility enhancement.

Poor solubility and hydrophobicity of drugs/bioactives limit their possible applications in drug delivery and formulation development. Apart from conventional methods of solubility enhancement, there are some novel methods which can be used in solubilization. Dendrimers represent a novel type of polymeric material that has generated much interest in many diverse areas due to their unique structure and properties. Dendrimer-mediated solubility enhancement mainly depends on factors such as generation size, dendrimer concentration, pH, core, temperature, and terminal functionality. Added advantage in solubilization can be achieved considering these factors. Available literature suggests that ionic interaction, hydrogen bonding, and hydrophobic interactions are the possible mechanisms by which a dendrimer exerts its solubilizing property. This review presents various mechanisms and reports relating to solubility enhancement using dendrimers. Also, micellar behavior and future possibilities in relation to solubilization via dendrimers are included.

Dendrimers↗

PubMed2006

Investigations on the toxicological profile of functionalized fifth-generation poly (propylene imine) dendrimer.

Dendrimers have generated tremendous interest in the field of drug delivery. Despite indications of their utility as drug carriers, the inherent cytotoxicity associated with polycationic dendrimers acts as a limiting factor to their clinical applications. Many functionalization strategies have been adopted to mask peripheral amines in order to overcome this limitation. The object of the present investigation was to evaluate the effect of functionalization on the toxicological profile of fifth-generation poly(propylene imine) dendrimer (PPI-5.0G). Four forms of functionalized dendrimers, including protected glycine and phenylalanine, and mannose and lactose functionalized poly(propylene imine) (PPI) dendrimer, were synthesized as prospective drug carriers. These dendrimeric systems were evaluated for haemolytic toxicity, cytotoxicity, immunogenicity and haematological parameters. PPI-5.0G demonstrated a positive charge-based time- and concentration-dependent toxicity profile. Functionalization greatly improved the toxicity profile of the parent dendrimer. Hence it is proposed that these functionalized forms of PPI dendrimer have great potential as bio-compatible drug vehicles.

Animals↗

PubMed2006

Sustained and targeted delivery of an anti-HIV agent using elastic liposomal formulation: mechanism of action.

The present study is aimed at evaluating the transdermal route as an alternative to the oral route for improving the systemic bioavailability and sustaining the constant therapeutic plasma level of Zidovudine (AZT). Elastic liposomal formulations of AZT were prepared and characterized. The effect of different formulation variables on transdermal delivery of AZT from elastic liposomes was studied. To investigate the mechanism of skin permeation of elastic liposomes, Transmission Electron Microscopic (TEM) study was carried out. The optimized elastic liposomal formulation showed transdermal flux of 98.8+/-5.8 microg/cm2/hr across rat skin as compared to 5.72+/-0.3 microg/cm2/hr for free drug. Vesicle-skin interaction study showed that elastic vesicles influenced the ultra structure of stratum corneum. Distinct regions with lamellar stacks derived from vesicles were observed in intercellular spaces of the stratum corneum. These stacks disrupted the organization of skin bilayers leading to increased skin permeability, whereas no changes were observed in the underlying viable epidermis and dermis. Improved pharmacokinetic profile was observed when AZT was entrapped in elastic liposomes. The AUC0-24h for elastic liposomal formulation was found to be (12.63+/-1.2 microg h/mL), nearly twelve fold higher than the control (0.83+/-0.2 microg h/mL). Furthermore, the administration of elastic liposome encapsulated AZT resulted in substantially higher accumulation of AZT in target RES organs that play a key role in the pathogenesis of AIDS by providing long-term reservoir for the virus. The results of the present study demonstrated that elastic liposomes increased the transdermal flux, prolonged the release, improved the site specificity of AZT and represented an attractive strategy for sustained and targeted delivery of AZT.

Administration, Cutaneous↗

PubMed2005

Calcium silicate based microspheres of repaglinide for gastroretentive floating drug delivery: preparation and in vitro characterization.

Gastroretentive dosage forms have potential for use as controlled-release drug delivery systems. Multiple unit systems avoid the 'all-or-none' gastric emptying nature of single-unit systems. A controlled release system designed to increase its residence time in the stomach without contact with the mucosa was achieved through the preparation of floating microspheres by the emulsion solvent diffusion technique consisting of (i) calcium silicate (FLR) as porous carrier; (ii) repaglinide, an oral hypoglycemic agent; and (iii) Eudragit S as polymer. The effect of various formulation and process variables on the internal and external particle morphology, micromeritic properties, in vitro floating behavior, physical state of the incorporated drug, drug loading and in vitro drug release were studied. The microparticles were found to be regular in shape and highly porous. The release rate was determined in simulated gastro-intestinal fluids at 37 degrees C. The formulation demonstrated favorable in vitro floating and release characteristics. The drug encapsulation efficiency was high. Incorporation of FLR in the microspheres proved to be an effective method to achieve the desired release behavior and buoyancy. The designed system, combining excellent buoyant ability and suitable drug release pattern, could possibly be advantageous in terms of increased bioavailability of repaglinide.

Algorithms↗

PubMed2005

Pegylated lysine based copolymeric dendritic micelles for solubilization and delivery of artemether.

PURPOSE: A newer polymeric amphiphilic micellar system was developed in the present study for solubilization and controlled delivery of an antimalarial drug, Artemether (ART). Methoxy polyethylene glycol (MPEG) 2000 and 5000 were used as hydrophilic terminal. METHODS: The hydrophobic di-Fluorene methoxycarbonyl-l-lysine (di-FMOC-L-lysine) was linked initially to the single reactive end of MPEG, and to the two amino groups of l-lysine by consecutive peptide linkages and deprotection upto 2.5 generations (G). Half-generations are diFMOC-lysine terminated systems and full-generations are deprotected l-lysine terminated systems. The half-generation (0.5 G, 1.5 G and 2.5 G) dendritic micelles of MPEG 2000 and 5000 were used to solubilize artemether. IR, NMR and Mass spectroscopy characterized the synthesis of these micellar systems. The CMC of the systems was determined. Then formulations made were characterized for solubility enhancement (i.e. drug loading) and drug-release profile. RESULTS: There is considerable solubility enhancement of artemether upto three to fifteen times depending on concentration, generation and type of dendritic micelles used. The size and shape were studied using transmission electron microscopy. The stability of the micellar formulation was also determined by storing the micelles at various temperatures for a definite period of time followed by its successive dilutions. The dendritic carriers were found to form stable micelles at 10-30 microg/ml (lower CMCs) depending on generation and type of MPEG used. The formulations increased the stability of the drug and also prolonged the release of artemether upto 1-2 days in vitro. CONCLUSION: From all the studies performed, it can be concluded that these micellar systems can be used for the safe and effective delivery of insoluble bioactive.

Artemether↗

PubMed2005

Lipid microparticles for mucosal immunization against hepatitis B.

Parenteral administration of vaccines often does not lead to optimal or long lasting protection against disease causing organisms particularly those that are inhaled, ingested or sexually transmitted. For optimal mucosal protection induction of immune response via mucosal routes is therefore highly desirable. Double emulsion-solvent evaporation (w/o/w) method best suited for water-soluble bioactives was selected for the preparation of hepatitis B surface antigen (HBsAg) loaded lipid microparticles. Intranasal route was considered for mucosal administration and hence to prepare the delivery system biocompatible and least irritable, soyalecithin (phospholipid) was taken instead of polymer because phosphatidylcholine is the major component of endogenous lung surfactant. The studies performed in present work included antigen characterization, development of lipid microparticles, stability studies of the prepared lipid microparticle formulations, percent mucoadhesion, ex vivo cellular uptake studies and in vivo studies. The general order obtained from in vivo studies for mucosal immune response (IgA) followed the sequence: LMST-HBsAg (IN)>LM-HBsAg (IN)>alum-HBsAg (IN)>LMST-HBsAg (IM)>alum-HBsAg (IM)>or=LM-HBsAg (IM)>plain HBsAg (IN)>plain HBsAg (IM).

Administration, Intranasal↗

PubMed2005

Glycodendrimeric nanoparticulate carriers of primaquine phosphate for liver targeting.

In the present study it was intended to deliver primaquine phosphate (PP), a liver schizonticide directly to liver cells using polypropyleneimine (PPI) dendrimers-coated peripherally with galactose. PPI dendrimers were synthesized by consecutive Michael double addition reaction (using ethyelenediamine as core), followed by hydrogenation reaction. Galactose conjugation was carried out by ring opening reactions, followed by Schiff's reaction and reduction to secondary amine in sodium acetate buffer (pH 4.0). IR, NMR, MASS spectroscopy were used for the confirmation of synthesis of uncoated and coated dendrimers. The formulations were made by equilibrium dialysis of dendrimers with the solution of PP. Then the formulations were characterized by TEM for size and shape. Release rate, hemolytic toxicity; bio-distribution and blood level studies were also performed on lyophilized formulations. The results obtained indicated that galactose coating of PPI systems increases the drug entrapment efficiency by 5-15 times depending upon generations. Galactose coating prolonged release up to 5-6 days as compared to 1-2 days for uncoated PPI systems. The hemolytic toxicity, blood level and hematological studies proved these systems to be safer and suitable for sustained drug delivery. Blood level studies proved the suitability of the systems for the prolonged circulations and delivery of PP to liver. The galactose coating of PPI dendrimers can therefore make the PPI systems more effective and suitable for targeted delivery of Primaquine phosphate to liver.

Animals↗

PubMed2005

Transdermal delivery of an analgesic agent using elastic liposomes: preparation, characterization and performance evaluation.

The aim of the present study was to prepare and characterize novel vesicular carrier elastic liposomes, of most commonly used non-steroidal anti-inflammatory agent diclofenac for its sustained and targeted delivery. Elastic liposomes of diclofenac were prepared and characterized in vitro and in vivo. The effect of different formulation variables like type of surfactant, concentration of surfactant and dose of drug on transdermal flux, amount of drug deposited into the skin, muscle and plasma concentration was investigated. The biological activity of optimized formulation was evaluated using carrageenan induced rat paw edema model and results were compared with commercial hydrogel formulation. The elastic liposomal formulations achieved muscle drug concentration between 2.2+/-0.14 to 5.3+/-0.22 microg/g at 12 hr. The same dose of commercial hydrogel formulation produced drug levels between 0.41+/-0.07 to 1.1+/-0.09 microg/g in the muscle. Plasma concentration study showed regiospecificity of elastic liposomal formulation. The results of in vivo study revealed that incorporation of diclofenac in elastic liposomes increased its biological activity two fold as compared to commercial hydrogel formulation. The results of the present study demonstrated greater effectiveness of dermaly applied diclofenac elastic liposomal formulation in comparison to conventional delivery system. The optimized elastic liposomal formulation offers a promising means for the non-invasive treatment of local pain and inflammation by topical application.

Administration, Cutaneous↗

PubMed2005

Possible analgesic and anti-inflammatory interactions of aspartame with opioids and NSAIDs.

The purpose of the present study was to investigate analgesic and anti-inflammatory properties of aspartame, an artificial sweetner and its combination with various opioids and NSAIDs for a possible synergistic response. The oral administration of aspartame (2-16mg/kg, po) significantly increased the pain threshold against acetic acid-induced writhes in mice. Co-administration of aspartame (2mg/kg, po) with nimesulide (2 mg/kg, po) and naproxen (5 mg/kg, po) significantly reduced acetic acid-induced writhes as compared to effects per se of individual drugs. Similarly when morphine (1 mg/kg, po) or pentazocine (1 mg/kg, po) was co-administered with aspartame it reduced the number of writhes as compared to their effects per se. Aspartame (4,8,16 mg/kg, po) significantly decreased carrageenan-induced increase in paw volume and also reversed the hyperalgesic effects in rats in combination with nimesulide (2 mg/kg, po). The study indicated that aspartame exerted analgesic and anti-inflammatory effects on its own and have a synergistic analgesic response with conventional analgesics of opioid and non-opioid type, respectively.

Acetic Acid↗

PubMed2004

Receptor-mediated targeting of lipobeads bearing acetohydroxamic acid for eradication of Helicobacter pylori.

In the present context, phosphatidyl ethanolamine (PE) liposomes anchored polyvinyl alcohol (PVA) xerogel beads (lipobeads) bearing acetohydroxamic acid (AHA) was developed as a receptor-mediated drug delivery system for use in blocking adhesion of Helicobacter pylori and thereby preventing the sequelae of chronic gastric infections. PVA beads containing AHA were prepared by emulsification followed by low temperature crystallization method. Surface acylation with fatty acid chain was accomplished by treating PVA bare beads with palmitoyl chloride. The completion of this reaction was characterized by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) which confirmed the formation of an ester bond. Final formation of lipobeads was accomplished by combining acylated PVA beads with a PE liposome suspension. To confirm the specific binding propensity of lipobeads towards the PE specific surface receptors of H. pylori, we have performed in situ adherence assay and radiolabelling assay with human stomach cells and KATO-III cells, respectively. In both of these studies, pretreatment of H. pylori with lipobeads completely inhibited the adhesion of H. pylori to human stomach cells and KATO-III cells. These assays could serve as suitable in-vitro models for the study of binding efficacy of lipobeads with H. pylori surface receptors. In addition, the antimicrobial activity of the formulations was evaluated by growth inhibition (GI) studies with isolated H. pylori strain. The inhibitory efficacy of lipobeads was significantly higher compared to that of PVA bare beads. These results suggest that lipobeads could be a potential targeted drug delivery system in the treatment of H. pylori.

Bacterial Adhesion↗

PubMed2004

Hydrotropic solubilization of nimesulide for parenteral administration.

Nimesulide is a non-steroidal anti-inflammatory drug (NSAID) that exhibits analgesic, antipyretic and anti-inflammatory activities. It is practically insoluble in water. The effect of various hydrotropes such as nicotinamide, sodium ascorbate, sodium benzoate, sodium salicylate and piperazine on the solubility of nimesulide was investigated. The solubility enhancement of nimesulide by the hydrotropes was observed in decreasing order as piperazine > sodium ascorbate > sodium salicylate > sodium benzoate > nicotinamide. In order to elucidate the probable mechanism of solubilization, various solution properties of hydrotropes such as viscosity, specific gravity, surface tension, refractive index, specific conductance of hydrotropic solutions were studied at 25 +/- 2 degrees C on the basis of earlier studies. The hydrotropic solubilization of nimesulide at lower hydrotrope concentration may be attributed to weak ionic interactions while that at higher hydrotrope concentration may be due to molecular aggregation. Parenteral formulations using piperazine as a hydrotrope were developed and studied for physical and chemical stability.

Infusions, Parenteral↗

PubMed2003

Diethylene glycol poisoning in Gurgaon, India, 1998.

OBJECTIVE: To discover the cause of acute renal failure in 36 children aged 2 months to 6 years who were admitted to two hospitals in Delhi between 1 April and 9 June 1998. METHODS: Data were collected from hospital records, parents and doctors of the patients, and district health officials. Further information was obtained from house visits and community surveys; blood and stool samples were collected from other ill children, healthy family members and community contacts. Samples of drinking-water and water from a tube-well were tested for coliform organisms. FINDINGS: Most of the children (26/36) were from the Gurgaon district in Haryana or had visited Gurgaon town for treatment of a minor illness. Acute renal failure developed after an episode of acute febrile illness with or without watery diarrhoea or mild respiratory symptoms for which the children had been treated with unknown medicines by private medical practitioners. On admission to hospital the children were not dehydrated. Median blood urea concentration was 150 mg/dl (range 79-311 mg/dl) and median serum creatinine concentration was 5.6 mg/dl (range 2.6-10.8 mg/dl). Kidney biopsy showed acute tubular necrosis. Thirty-three children were known to have died despite being treated with peritoneal dialysis and supportive therapy. CONCLUSION: Cough expectorant manufactured by a company in Gurgaon was found to be contaminated with diethylene glycol (17.5% v/v), but a sample of acetaminophen manufactured by the same company tested negative for contamination when gas-liquid chromatography was used. Thus, poisoning with diethylene glycol seems to be the cause of acute renal failure in these children.

Acute Kidney Injury↗

PubMed2003

Dendrimer-mediated transdermal delivery: enhanced bioavailability of indomethacin.

The transdermal delivery of aqueous formulations of indomethacin, a model drug, with different concentrations of three types of dendrimer showed a linear increase in flux with increasing concentration of each of the dendrimers. This result was in contrast to phase solubility studies, where Higuchi's A(N) profile was observed. The steady-state flux of the drug increased significantly and was highest with the G4-NH2 dendrimer at 0.2% w/v concentration, which showed an enhancement factor of 4.5 compared to the pure drug suspension. In vivo, a steady-state flux was achieved in 5 h, and the C(max) values were significantly higher with G4-NH2 and G4-OH dendrimer formulations. The [AUC](0-24h) of G4-NH2 (2.27 times) and G4-OH (1.95 times) formulations were significantly higher than that of the pure drug, but was only marginally higher in the case of G-4.5 dendrimer formulation. The % inhibition of paw volume showed a trend comparable to the pharmacokinetic data and a maximum of 1.6- and 1.5-fold increase was found with G4-NH2 and G4-OH formulations, respectively, compared to the pure drug suspension.

Administration, Cutaneous↗

PubMed2003

A PEGylated dendritic nanoparticulate carrier of fluorouracil.

The present study was aimed at developing and exploring the use of uncoated and PEGylated newer PAMAM dendrimers for delivery of anti-cancer drug 5-fluorouracil. For this study, successive Michael addition and exhaustive amidation reactions were used to synthesize 4.0 G PAMAM dendrimers, using ethylenediamine as core and methylmethacrylate as propagating agent. The dendrimer was PEGylated using N-hydroxysuccinimide-activated carboxymethyl MPEG-5000. IR and NMR data proved the synthesis. Various physicochemical parameters, SEM, TEM, lambda(max) values, hemolytic toxicity, drug entrapment, drug release and blood-level studies of both PEGylated and non-PEGylated systems were determined and compared. The PEGylation of the systems was found to have increased their drug-loading capacity, reduced their drug release rate and hemolytic toxicity. TEM study revealed surface properties of the systems. Stability studies had shown its stability at room temperature in dark. The systems were found suitable for prolonged delivery of an anti-cancer drug by in vitro and blood-level studies in albino rats, without producing any significant hematological disturbances. PEGylation has been found to be suitable for modification of PAMAM dendrimers for reduction of drug leakage and hemolytic toxicity. This, in turn, could improve drug-loading capacity and stabilize such systems in body. The study suggests use of such PEGylated dendrimeric systems as nanoparticulate depot type of system for drug administration.

Animals↗

PubMed2003

Electrochemical analysis and analgesic behavior of Zn(II)-baclofen complex.

The electroanalytical behavior of Zn(II)-baclofen complex has been described by direct current polarographic (DCP) method. The complex of transition metal Zn(II) with baclofen, [4-amino-3(4-chlorophenyl) butanoic acid, has been prepared and characterized on the basis of elemental analysis, IR-spectral, polarographic and amperometric studies. The metal-ligand interaction in aqueous medium has been studied polarographically at 25 degrees C and at an ionic strength of mu = 1.0 M KCl. The reduction of the complex was found to involve two electrons and of diffusion controlled nature. The analytical results indicated a 1:1 (M:L) stoichiometry for Zn(II)-baclofen complex. The results on the drug and drug-metal complex revealed that the complex is more potent as compared with the parent drug.

Analgesics↗