ABSTRACT
The contraceptive properties of a gel formulation containing sodium lauryl sulfate were investigated in both in vitro and in vivo models. Results showed that sodium lauryl sulfate inhibited, in a concentration-dependent manner, the activity of sheep testicular hyaluronidase. Sodium lauryl sulfate also completely inhibited human sperm motility as evaluated by the 30-sec Sander-Cramer test. The acid-buffering capacity of gel formulations containing sodium lauryl sulfate increased with the molarity of the citrate buffers used for their preparations. Furthermore, experiments in which semen was mixed with undiluted gel formulations in different proportions confirmed their physiologically relevant buffering capacity. Intravaginal application of the gel formulation containing sodium lauryl sulfate to rabbits before their artificial insemination with freshly ejaculated semen completely prevented egg fertilization. The gel formulation containing sodium lauryl sulfate was fully compatible with nonlubricated latex condoms. Taken together, these results suggest that the gel formulation containing sodium lauryl sulfate could represent a potential candidate for use as a topical vaginal spermicidal formulation to provide fertility control in women.
Subject(s)
Sodium Dodecyl Sulfate/pharmacokinetics , Spermatocidal Agents , Animals , Buffers , Chemistry, Pharmaceutical , Condoms , Gels , Humans , Hyaluronoglucosaminidase/metabolism , Hydrogen-Ion Concentration , In Vitro Techniques , Male , Nonoxynol/pharmacology , Rabbits , Sheep , Sodium Dodecyl Sulfate/administration & dosage , Sodium Dodecyl Sulfate/chemistry , Sperm Motility/drug effects , Spermatozoa/drug effects , Spermatozoa/enzymologyABSTRACT
The tissue distribution of indinavir, free or incorporated into sterically stabilized anti-HLA-DR immunoliposomes, has been evaluated after a single subcutaneous injection to C3H mice. Administration of free indinavir resulted in low drug levels in lymphoid organs. In contrast, sterically stabilized anti-HLA-DR immunoliposomes were very efficient in delivering high concentrations of indinavir to lymphoid tissues for at least 15 days post-injection increasing by up to 126 times the drug accumulation in lymph nodes. The efficacy of free and immunoliposomal indinavir has been evaluated in vitro. Results showed that immunoliposomal indinavir was as efficient as the free agent to inhibit HIV-1 replication in cultured cells. The toxicity and immunogenicity of repeated administrations of liposomal formulations have also been investigated in rodents. No significant differences in the levels of hepatic enzymes of mice treated with free or liposomal indinavir were observed when compared to baseline and control untreated mice. Furthermore, histopathological studies revealed no significant damage to liver and spleen when compared to the control group. Liposomes bearing Fab' fragments were 2.3-fold less immunogenic than liposomes bearing the entire IgG. Incorporation of antiviral agents into sterically stabilized immunoliposomes could represent a novel therapeutic strategy to target specifically HIV reservoirs and treat more efficiently this retroviral infection.
