[Show abstract][Hide abstract] ABSTRACT: A novel series of N-Mannich bases of benzimidazole derivatives were synthesized and characterized by (1)H NMR, IR spectral studies and elemental analysis. The compounds were screened for analgesic and anti-inflammatory activity. 1-((Diethylamino)-methyl)-2-styryl benzimidazole 4 at 40mg/kg was found to be equipotent to paracetamol. 1-((Piperidin-1-yl) methyl)-2-styryl-benzimidazole 6 at 40mg/kg was found to be more potent than Diclofenac. Corneal permeability and quantum chemical calculations were performed to correlate the hydrogen bonding ability with permeability and activity. The energies of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) were correlated with pharmacological activity. The semi-empirical PM3 calculations (quantum chemical calculations) revealed that E(LUMO) and energy gap DeltaE were capable of accounting for the high in vitro bovine corneal permeability and activity of the compounds.
European journal of medicinal chemistry 05/2008; 44(5):2307-12. · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A controlled-release drug delivery of contraceptive steroids levonorgestrel (LNG) and ethinyl estradiol (EE) has been developed by successful encapsulation of LNG and EE in poly (lactide-co-glycolide) (PLG) microspheres.
Smooth, spherical, steroid-loaded PLG microspheres with a mean size of 10-25 microm were prepared by using the water/oil/water double-emulsion solvent evaporation method.
In vitro release profiles showed an increased burst release of LNG/EE on Week 1; thereafter, the release was sustained. At the end of Week 7, the release of LNG/EE from 1:5 and 1:10 PLG microspheres was 75.64% and 62.55%. respectively. In vitro degradation studies showed that the PLG microspheres maintained surface integrity up to Week 8 and then eroded completely by Week 20. In an in vivo study, the serum concentration of LNG/EE in rats showed a triphasic release response, with an initial burst release of 8 ng/mL LNG and 14 pg/mL EE on Day 1; thereafter, a controlled release of the drugs to the systemic circulation was maintained until Week 15, maintaining constant drug levels of 2 ng/mL LNG and 3-4 pg/mL EE in the blood. Histological examination of steroid-loaded PLG microspheres injected intramuscularly into the thigh muscle of Wistar rats showed minimal inflammatory reaction, demonstrating that contraceptive-steroid-loaded microspheres were biocompatible.
This controlled-release and biocompatible nature of the PLG microspheres may have potential application in contraceptive therapy.
[Show abstract][Hide abstract] ABSTRACT: Oral hepatitis B vaccine formulation was prepared by successful encapsulation of immunogenic peptide representing residues 127-145 of the immunodominant B-cell epitope of hepatitis B surface antigen (HBsAg) in poly(D,L-lactide co-glycolide) (PLG) microparticles. The smooth, spherical PLG microparticles with a diameter of around 10 microm was prepared by using W/O/W double emulsion solvent evaporation method. The entrapment efficiency of B-cell epitope peptide (BCEP) into PLG microparticles was 64%. In vitro studies showed B-cell epitope loaded PLG microparticles (BCEM) released the peptide in sustained profile and reached 64.9% efficiency by Day 25. Single oral immunization of mice with BCEM led to the significant induction of specific serum IgG and IgM anti-HB antibodies. After the termination of antibody induction, the orally immunized mice were infected with HBsAg, which resulted in the rapid production of antibodies against HBsAg as a result of secondary immune response. PLG microparticles formulation approach may have potential in increasing the efficacy of microparticulate systems for the oral administration of hepatitis B vaccine.
[Show abstract][Hide abstract] ABSTRACT: A reconstituted collagen scaffold impregnated with silver sulfadiazine (SSD) loaded alginate microspheres, capable of delivering the drug in a controlled manner has been developed. SSD-loaded alginate microspheres were prepared by modified water-in-oil emulsion technique through interfacial ionic gelation of alginate using CaCl2. The SSD-loaded microspheres were impregnated in pepsin-solubilized collagen, in situ, while inducing fibrillation and cast as thin scaffold. Morphological features of microspheres and microsphere-impregnated collagen were analyzed through SEM. Distribution homogeneity of impregnated microspheres, their in vitro behavior in (Dulbecco's modified minimal essential media) DMEM, and antibacterial efficiency against ATCC pathogens were determined. Initial drug load of 20% (w/w) with respect to alginate and 40% (v/v) of 2% alginate with respect to oil phase were found to produce microspheres of optimum drug entrapment (3%) and required size range (300-370 microm). In vitro drug release studies from the scaffold showed an initial burst release of 47.5% and a controlled release for 72 h with equilibrium concentration of 68.8%. SSD-loaded microspheres exhibited minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) levels of 32 and 40.2 microg/mL to both K. pneumoniae and E. coli respectively. P. aeruginosa showed MIC and MBC levels of 44.8 and 51.2 microg/mL respectively, while Staphylococcus aureus exhibited MIC and MBC at the same concentration range (57.6 microg/mL). The collagen-based scaffold impregnated with SSD-loaded alginate microspheres can deliver SSD in a controlled fashion, can control infection for extended time period with lesser dressing frequencies, and will enable easier assessment of wound.
Journal of Biomedical Materials Research Part B Applied Biomaterials 06/2006; 77(2):378-88. · 2.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The use of peptide-based drugs is limited by their rapid degradability and toxicity at high concentration during their therapeutic application. These problems could be managed by the use of a peptide delivery agent for sustained release in the site of action. Collagen is one of the most proven biomaterials of good biocompatibility with an exceptional ligand encapsulating property. In this work, we have shown that pexiganan, an antimicrobial, 22-amino-acid peptide could be incorporated and delivered to the wound-healing site against bacterial strains Pseudomonas aeruginosa and Staphylococcus aureus. The release profiles of pexiganan collagen films with different collagen concentration were studied. The release of pexiganan from 2.5% w/w of collagen film showed a sustainable activity over 72 h with effective antimicrobial concentrations. Pexiganan-incorporated collagen (PIC)-treated groups were compared with open wound (OW)- and collagen film (CF)-treated rats. PIC-treated animals showed a diminishing level of bacterial growth as compared with OW- and CF-treated animals. The biochemical parameters such as hydroxyproline, protein, DNA, uronic acid, hexosamine, SOD, and catalase content in the granulation tissue of the healing wound revealed increased proliferation of cells involved in tissue reconstruction in PIC-treated groups when compared with OW- and CF-treated groups. Furthermore, spectroscopic studies suggested that collagen structure is not perturbed by pexiganan incorporation. This study provides rationale for application of collagen membrane for antimicrobial peptide delivery in infected wounds.
Journal of Biomedical Materials Research Part A 07/2005; 73(3):320-31. · 2.83 Impact Factor