M. Melissa Peet

Broadly neutralizing antibodies (bnAbs) are advancing as a preventative or treatment option for HIV infection, but currently must be administered parenterally, typically as a large injection or infusion, an invasive method of delivery, especially for the pediatric population. Here, we present proof-of-concept data on a minimally invasive microneedle (MN) patch platform codelivering three bnAbs, PGT121, VRC07-523LS, and PGDM1400LS, from separate MN patch units or pixels. Each 1 cm2 patch pixel, fabricated via solvent casting, contained ∼2 mg of one bnAb. In ex vivo porcine skin tests, the MNs effectively penetrated the skin. When tested in vitro in PBS buffer, MNs quickly dissolved, fully releasing bnAbs within 10 min. VRC07-523LS and PGT121 functionality was maintained during patch manufacturing, as confirmed by an in vitro HIV-1 neutralization assay, while PGDM1400LS lost some potency. In a rat model, coadministration of 1 cm2 patch units for each bnAb resulted in systemic exposure by the first collection time point of 3 h, reaching maximal concentrations by day 3 of up to 68 μg/mL. These preliminary findings suggest that the MN patch platform may serve as a promising alternative to injectable bnAb formulations for HIV prevention and treatment, particularly in neonates and infants, although further investigation is required to establish its clinical utility. Additionally, the solid-state MN formulation of bnAbs may eliminate the need for cold-chain storage or distribution, making the patch particularly suitable for use in resource-limited settings.

Despite advances in oral and injectable HIV prevention options and oral prophylaxis for sexually transmitted infections (STIs) of bacterial origin, there remains a critical need for effective on-demand topical (vaginal and rectal) products for pre- and post-exposure prophylaxis (PrEP and PEP). To fill this gap, we have developed single and first-in-kind multi-active topical inserts for bacterial STIs and HIV/STIs prevention. We have formulated two different inserts, one containing doxycycline (DOX) at 10, 50, and 100 mg doses for bacterial STI prevention, and a multipurpose prevention product (TED insert) that combines DOX (10 mg) with the antiretrovirals tenofovir alafenamide (TAF; 20 mg) and elvitegravir (EVG; 16 mg) to target both bacterial STIs and HIV. Inserts were manufactured using a simple and cost-effective process. Drug loading was within 95-105% of the labeled amount, confirming a robust manufacturing process. In vitro, the inserts disintegrated within 10 min with > 95% drug release within 60 min. The dissolution behavior of DOX inserts showed surface erosion but was affected by medium volume and drug amount. The inserts met key physicochemical targets: hardness (5-8 kg), friability (< 1%), moisture content (< 2%), and osmolality (< 550 mOsm/kg). Based on 6-month storage stability, DOX inserts maintained their physicochemical properties, indicating a shelf life of > 2 years. Preliminary 1-month stability of TED inserts under accelerated conditions showed preservation of their physicochemical properties. These data describe the formulation development and in vitro characterization of topical inserts containing DOX alone or in combination with antiretrovirals (TAF and EVG). Both inserts offer a novel, on-demand topical STI prevention option that supports flexible PrEP/PEP use by both women and men.

Purpose: Despite advances in oral and injectable HIV prevention options and oral prophylaxis for sexually transmitted infections (STIs) of bacterial origin, there remains a critical need for effective on-demand topical (vaginal/rectal) products for pre- and post-exposure prophylaxis (PrEP and PEP). To fill this gap, we have developed single and first-in-kind multi-active topical inserts for bacterial STIs and HIV/STIs prevention. Methods: We have formulated two different inserts, one containing doxycycline (DOX) at 10, 50, and 100mg doses for bacterial STI prevention, and a multipurpose prevention product (TED insert) that combines DOX (10mg) with the antiretrovirals tenofovir alafenamide (TAF; 20mg) and elvitegravir (EVG; 16mg) to target both bacterial STIs and HIV. Results: Inserts were manufactured through a simple, cost-effective process. Drug loading was within 95-105% of the labeled amount, confirming a robust manufacturing process. In vitro, they disintegrated within 10min with >95% drug release within 60min. The dissolution behavior of DOX inserts showed surface erosion but was affected by medium volume and drug amount. The inserts met key physicochemical targets: hardness (5-8kg), friability (<1%), moisture content (<2%), and osmolality (2years. Preliminary 1-month stability of TED inserts under accelerated conditions showed preservation of their physicochemical properties. Conclusion: This study represents the first formulation development report on topical inserts containing DOX alone or in combination with antiretrovirals. Both inserts offer a novel, on-demand topical STI prevention option that supports flexible PrEP/PEP use by both women and men.