Juvenile hormone synthesis in vitro by larval and pupal corpora allata of Manduca sexta.

The synthesis of juvenile hormone I (JH I) and juvenile hormone III (JH III) in vitro by isolated corpora allata (CA) and brain-corpora cardiaca-corpora allata complexes (BR-CC-CA) from fourth and fifth instar larvae and pupae of Manduca sexta was assessed by JH I and JH III radioimmunoassays of incubation medium. Fluctuations in synthesis occurred at specific stages during larval-pupal development. These fluctuations temporally approximated those of previously determined hemolymph titers of JH I and III for this developmental period, except for the synthesis of JH III during the prepupal period, when the JH III hemolymph titer was negligible but JH III synthesis in vitro increased to the highest rate observed. The overall agreement between CA activity and the JH hemolymph titers suggests that the in vitro system supports physiological gland activity and that changes in biosynthesis contribute significantly to changes in the titers. A comparison of JH I and JH III synthesis by isolated CA with that by BR-CC-CA suggests that the BR-CC can differentially modulate the synthesis of these two homologs. The significance of these findings with regard to the possible endocrine function of JH III and the proposed neuroendocrine control of the CA is discussed.

Topical delivery of growth hormone releasing peptide using liposomal systems: an in vitro study using hairless mouse skin.

The results of this study clearly demonstrates the utility of novel non-ionic liposomal systems in facilitating transfer of GHRP-6 into and across deeper strata of skin following topical application. These findings indicate that it may be possible to deliver therapeutic doses of a wide variety of peptides to local skin tissue via topical application. The results also suggest the possibility of controlled enhancement of skin penetration or metered polypeptide deposition through appropriate choice of liposomal lipid components. The pronounced enhancement of GHRP-6 and mannitol transport from emulsions containing the nonionic lipids suggests a promising delivery system for hydrophilic drugs in general.

Perifollicular transgenic expression of human interleukin-1 receptor antagonist protein following topical application of novel liposome-plasmid DNA formulations in vivo.

Expression plasmid DNA for the human interleukin-1 receptor antagonist (IL-1ra) protein was formulated with nonionic:cationic (NC) liposomes or phosphatidylcholine:cationic (PC) liposomes and applied to the auricular skin of hamsters in single- and multiple-dose protocols. Confocal microscopy identified delivery of plasmid DNA proximal to perifollicular cells, and successful transfection of perifollicular cells was identified by immunohistochemistry and ELISA. Skin treated for 3 days with the NC liposomes had statistically significant levels of transgenic IL-1ra present for 5 days post-treatment. Expression of transgenic IL-1ra was specific to areas of skin treated with NC liposomes but not PC liposomes. The results indicate that the NC liposomes can deliver expression plasmid DNA to perifollicular cells and mediate transient transfection in vivo.

Influence of nonionic liposomal composition on topical delivery of peptide drugs into pilosebaceous units: an in vivo study using the hamster ear model.

PURPOSE: The purpose of this study was to test the hypothesis that nonionic liposomes facilitate the topical delivery of peptide drugs into pilosebaceous units. METHODS: The hamster ear was used as a model for human pilosebaceous units. The deposition of a hydrophilic protein, alpha-interferon (alpha-IFN), into pilosebaceous units and other strata of the hamster ear 12 hours after topical in vivo application of three nonionic liposomal formulations, one composed of glyceryl dilaurate/cholesterol/polyoxyethylene-10-stearyl ether (Non-1), the second composed of glyceryl distearate/cholesterol/polyoxyethylene-10-stearyl ether (Non-2) and the third composed of polyoxyethylene-10-stearyl ether/cholesterol (Non-3), a phospholipid-based liposomal formulation (PC) and an aqueous control solution (AQ) was determined. We also determined the deposition of a hydrophobic peptide, cyclosporin-A (CsA), into pilosebaceous units and other strata of the hamster ear after topical in vivo application of these liposomal formulations and a hydroalcoholic control solution (HA). RESULTS: The deposition of alpha-IFN into the pilosebaceous units was in the order: Non-1 >> PC > Non-2 > Non-3 = AQ. The deposition of CsA into the pilosebaceous units was in the order: Non-1 >> HA > PC > Non-2 = Non-3. CONCLUSIONS: Despite differences in the hydrophobicities and size of the drug molecules, deposition into the various ear strata was significantly enhanced by the Non-1 liposomal system.