PURPOSE: To develop spray dried mucoadhesive and pH-sensitive microspheres (MS) based on polymethacrylate salt intended for vaginal delivery of tenofovir (a model HIV microbicide) and assess their critical biological responses. METHODS: The formulation variables and process parameters are screened and optimized using a 2(4-1) fractional factorial design. The MS are characterized for size, zeta potential, yield, encapsulation efficiency, Carr's index, drug loading, in vitro release, cytotoxicity, inflammatory responses and mucoadhesion. RESULTS: The optimal MS formulation has an average size of 4.73μm, zeta potential of -26.3mV, 68.9% yield, encapsulation efficiency of 88.7%, Carr's index of 28.3 and drug loading of 2% (w/w). The MS formulation release 91.7% of its payload in the presence of simulated human semen. At a concentration of 1mg/ml, the MS are noncytotoxic to vaginal endocervical/epithelial cells and Lactobacillus crispatus when compared to control media. There is also no statistically significant level of inflammatory cytokine (IL1-α, IL-1β, IL-6, IL-8, and IP-10) release triggered by these MS. Their percent mucoadhesion is 2-fold higher than that of 1% HEC gel formulation. CONCLUSION: These data suggest the promise of using such MS as an alternative controlled microbicide delivery template by intravaginal route for HIV prevention.
PURPOSE: To develop spray dried mucoadhesive and pH-sensitive microspheres (MS) based on polymethacrylate salt intended for vaginal delivery of tenofovir (a model HIV microbicide) and assess their critical biological responses. METHODS: The formulation variables and process parameters are screened and optimized using a 2(4-1) fractional factorial design. The MS are characterized for size, zeta potential, yield, encapsulation efficiency, Carr's index, drug loading, in vitro release, cytotoxicity, inflammatory responses and mucoadhesion. RESULTS: The optimal MS formulation has an average size of 4.73μm, zeta potential of -26.3mV, 68.9% yield, encapsulation efficiency of 88.7%, Carr's index of 28.3 and drug loading of 2% (w/w). The MS formulation release 91.7% of its payload in the presence of simulated human semen. At a concentration of 1mg/ml, the MS are noncytotoxic to vaginal endocervical/epithelial cells and Lactobacillus crispatus when compared to control media. There is also no statistically significant level of inflammatory cytokine (IL1-α, IL-1β, IL-6, IL-8, and IP-10) release triggered by these MS. Their percent mucoadhesion is 2-fold higher than that of 1% HEC gel formulation. CONCLUSION: These data suggest the promise of using such MS as an alternative controlled microbicide delivery template by intravaginal route for HIV prevention.
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