Search

Contraceptive steroids levonorgestrel (LNG) and ethinyl estradiol (EE) have been encapsulated with poly(ϵ-caprolactone) (PCL) microspheres using a w/o/w double emulsion method. The microspheres prepared were smooth and spherical, with a mean size from 8–25 μm. In vitro release profiles of microspheres showed a trend of increasing initially at the first week, and thereafter the release was sustained. At the end of the seventh week LNG/EE from 1:5 and 1:10 PCL microspheres were 60 and 48%, 52 and 46%, respectively. An in vitro degradation study shows that at the 20th week the microspheres maintained the surface integrity. The PCL microspheres showed a triphasic in vivo release profile with an initial burst effect due to the release of the steroid adsorbed on the microsphere surface, a second sustained release phase due to the steroid diffusion through the pores or channels formed in the polymer matrix, and third phase due to polymer bioerodible. Histological examination of PCL microspheres injected intramuscularly into thigh muscle of a rat showed a minimal inflammatory reaction demonstrating that contraceptive steroid-loaded microspheres were biocompatible. The level of inflammatory cytokines determined by immunostaining for IL-1α, the tissue response to formulations at the first week was considered mild, whereas at the end of the 20th week the inflammatory response ceased. Thus, this study helped us to evaluate the feasibility of using these microspheres as a long-acting biodegradable drug delivery system for contraceptive steroids. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006

Neurotrophic factors play an important modulatory role in axonal sprouting during nerve regeneration involving the proliferation of hematogenous and Schwann cells in damaged tissue. We have exposed lesioned sciatic nerves to a collagen prosthesis with covalently bonded small cell adhesive peptides Arg-Gly-Asp-Ser (RGDS), Lys-Arg-Asp-Ser (KRDS), and Gly-His-Lys (GHK) to study local production of growth factors and cytokines in the regenerating tissues. Western/enzyme-linked immunosorbent assay (ELISA) studies were performed after 10 days of regeneration, when the tubular prosthesis is filled with fibrous matrix infiltrated by hematogenous cells and proliferating Schwann cells with growth factors produced locally. Regeneration was also analyzed by morphometrical methods after 30 days. The quantification of growth factors and proteins by ELISA revealed that there was an enhanced expression of the neurotrophic factors nerve growth factor (NGF) and neurotrophins (NT-3 and NT-4) in the regenerating tissues. This was further established by Western blot to qualitatively analyze the presence of the antigens in the regenerating tissues. Schwann cells were localized in the regenerating tissues using antibodies against S-100 protein. Other growth factors including growth-associated protein 43 (GAP-43), apolipoprotein E (Apo E), and pro-inflammatory cytokine like interleukin-1alpha (IL-1alpha) expression in the peptide groups were evaluated by ELISA and confirmed by Western blotting. Cell adhesive integrins in the proliferating cells were localized using integrin-alpha V. The combined results suggest that the early phase of regeneration of peripheral nerves in the presence of peptide-incorporated collagen tubes results in the enhanced production of trophic factors by the recruited hematogenous cells and Schwann cells, which in turn help in the secretion of certain vital trophic and tropic factors essential for early regeneration. Furthermore, hematogenous cells recruited within the first 10 days of regeneration help in the production of inflammatory mediators like interleukins that in turn stimulate Schwann cells to produce NGF for axonal growth.

This study evaluated the effects of noncovalently incorporated crystallin into the collagen matrix for dermal wound-healing processes in rats. Crystallin-incorporated collagen matrix (CIC) showed better healing when compared to wounds treated with collagen matrix (CS) and without collagen (CR). Biochemical parameters and histological analysis revealed that increased wound contraction enhanced cell proliferation and efficient radical scavenging in the CIC group. The higher shrinkage temperature of CIC films when compared to CS groups suggested increased hydrothermal stability for the former material. An in vitro release study of CIC has showed sustained and time-dependent release of crystallin from the collagen matrix. These results demonstrate the possibility of using crystallin as therapeutic protein in the wound-healing process.

Amyloid β (Aβ) peptides are one of the classes of amphiphilic molecules that on dissolution in aqueous solvents undergo interesting conformational transitions. These conformational changes are known to be associated with their neuronal toxicity. The mechanism of structural transition involved in the monomeric Aβ to toxic assemblage is yet to be understood at the molecular level. Early results indicate that oriented molecular crowding has a profound effect on their assemblage formation. In this work, we have studied how different microenvironments affect the conformational transitions of one of the active amyloid β-peptide fragments (Aβ25–35). Spectroscopic techniques such as CD and Fourier transform infrared spectroscopy were used. It was observed that a stored peptide concentrates on dissolution in methanol adopts a minor α-helical conformation along with unordered structures. On changing the methanol concentration in the solvated film form, the conformation switches to the antiparallel β-sheet structure on the hydrophilic surface, whereas the peptide shows transition from a mixture of helix and unordered structure into predominantly a β-sheet with minor contribution of helix structure on the hydrophobic surface. Our present investigations indicate that the conformations induced by the different surfaces dictate the gross conformational preference of the peptide concentrate. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2004

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.