ABSTRACT
The objective of this study was to compare the haemostatic efficacy and foreign body reaction of epinephrine-impregnated cotton pellets with those of epinephrine-impregnated polyurethane (PU) foam cubes in osseous defects created in guinea pigs. Initially, these substances were randomly applied to the osseous defects in guinea pigs for 2 min and blood loss was measured. The animals were then sacrificed 7 weeks later and the degree of foreign body reaction was scored. The data were analysed by the independent-samples Kruskal-Wallis test. Epinephrine-impregnated PU foam cubes showed significantly better haemostatic effect compared to epinephrine-impregnated cotton pellets. The PU foam containing epinephrine specimens elicited significantly less foreign body reaction compared to epinephrine cotton pellets (P < 0.05). Based on the results of this study, it is concluded that epinephrine-impregnated PU foam cubes are a good alternative to epinephrine-impregnated cotton pellets as a local haemostatic agent in endodontic surgery.
Subject(s)
Dental Implantation, Endosseous, Endodontic/adverse effects , Epinephrine/administration & dosage , Foreign-Body Reaction/therapy , Hemostatic Techniques , Surgical Sponges , Animals , Chi-Square Distribution , Dental Implantation, Endosseous, Endodontic/methods , Disease Models, Animal , Guinea Pigs , Hemorrhage/prevention & control , Male , Polyurethanes , Random Allocation , Treatment OutcomeABSTRACT
PURPOSE: Use of coital-dependent products to prevent HIV-1 transmission has resulted in mixed success. We hypothesize that incorporation of antiviral drug candidates into a novel controlled delivery system will prolong their activity, making their use coital independent, thus increasing their chance of prophylactic success. METHODS: Tenofovir, emtricitabine, and C5A peptide HIV microbicides were mechanically incorporated into matrices comprising a series of subliming solids. Matrix sublimation rates and drug release rates were measured in three in vitro and one in vivo environments intended to model human vaginal interior. Antiviral activity studies evaluating matrix incorporated microbicides were performed using in vitro cell cultures and human ectocervical explants. RESULTS: Drug release rates were identical to matrix sublimation rates, and were zero order. Differences in matrix material sublimation enthalpies determined drug release and matrix erosion rates in a thermodynamically definable manner, in vitro and in vivo. Durations of release ranging from several days to several months were readily achieved. Prolonged duration of anti HIV-1 activity was shown for matrix incorporated microbicides, using ectocervical explant and cell culture models of HIV-1 infection. CONCLUSION: Subliming solid matrices show promise as a delivery system providing multi month intravaginal release of a wide range of HIV-1 microbicides.
Subject(s)
Anti-HIV Agents/administration & dosage , Anti-HIV Agents/chemistry , Drug Delivery Systems/methods , HIV Infections/prevention & control , Adenine/administration & dosage , Adenine/analogs & derivatives , Animals , Cells, Cultured , Contraceptive Devices, Female , Delayed-Action Preparations , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Emtricitabine , Female , HIV Infections/transmission , HIV-1/drug effects , Humans , Macrophages/drug effects , Monocytes/drug effects , Organophosphonates/administration & dosage , Sheep , Structure-Activity Relationship , Sublimation, Chemical , T-Lymphocytes/drug effects , TenofovirABSTRACT
We have identified a short amphipathic helical peptide, called C5A, which exhibits potent microbicidal activities in vitro and which offers protection from vaginal HIV transmission in vivo in a humanized mouse model. However, there are many obstacles to overcome before C5A can be considered a true microbicidal candidate. First, it must be stabilized against enzymatic degradation in a continuously warm and moist environment. Second, it must be delivered in a controlled manner to achieve long-term and coitally independent efficacy. We demonstrate in this in vitro study that the combination of two matrices with different subliming properties ((hexamethylcyclotrisiloxane [HMCS] and cyclododecane [CDD]) containing 10% labile C5A yielded the best results in terms of controlled release and preserved anti-HIV activity of the peptide when pre-exposed to cell-free medium or cell culture at body temperature for up to 2 months.
