(T1030-02-12) Nanoparticle in Rapidly Soluble Vaginal Film: A Promising Formulation for Pre-exposure Prophylaxis of HIV

Purpose: Acquired immunodeficiency syndrome (AIDS) is a chronic, potentially life-threatening condition caused by the human immunodeficiency virus (HIV). HIV infection is a global health pandemic affecting nearly 38.4 million people worldwide as of 2021. Transmission of HIV majorly occurs in presence of specific bodily fluid acting as vectors carrying the viral load. HIV destroys memory CD4 T-cells that have been primed to rapidly respond to infections. HIV transmission can be prevented with locally delivered pre-exposure prophylaxis (PrEP). PrEP is a course of HIV drugs taken by HIV-negative people to prevent infection. PrEP was created for those who may be at risk of contracting HIV from sex. Nanosuspension (NS) is a unique system comprising of drugs and stabilizers providing nano-range particle size, generally ranging from 10 to 1000 nm. Therefore, the purpose is to develop Maraviroc loaded NS. Maraviroc is a weakly basic molecule and CCR5 co-receptor antagonist while soluplus is an amphiphilic polymer to form a rapidly soluble nano complex. The objective of this study is: (a) To formulate and evaluate MVC NS and (b) To develop and characterize the MVC NS loaded rapidly soluble topical vaginal film.

Methods: An organic solvent-free, top-down nano-milling process was used to prepare MVC NS. Different stabilizers were screened to optimize the stability of the formulation. The NS were prepared using stabilizers such as Hydroxypropyl methylcellulose, Anionic Pullulan, and Soluplus. The nano-milling was carried out using 0.3 mm zirconium beads in NETZSCH DeltaVita® (Figure 1a). The optimized batch of MVC NS containing 1% MVC stabilized using 2% soluplus was analyzed for further studies. The particle size, poly dispersibility index (PDI), and zeta potential of the formulations were analyzed by Malvern zeta sizer. Furthermore, High performance liquid chromatography (Waters alliance system equipped with 2998 PDA) method was developed for analysis of Maraviroc retained in the NS. Finally, MVC NS were dispersed in Polyvinyl alcohol (PVA) based polymeric matrix and casted as a film using glycerol by the solvent evaporation method. We are further testing formulation with its cytotoxicity, cell membrane integrity, anti-HIV replication assay and in-vitro release profile of film.

Results: Nanosuspensions prepared with different stabilizers showed sedimentation over a period of time. The phase separation was found in batches prepared with HPMC, Anionic Pullulan. The particle size of these batches resulted in the bimodal or multimodal distribution leading to unstable batches of nanosuspension (Figure 1b-c). The MVC NS with soluplus showed unimodal distribution of the particles (Figure 1d). The optimized MVC NS consisting of soluplus depicted a particle size of 98 ± 0.2 nm with PDI of 0.152 ± 0.147. Over a period, the MVC NS consisting of soluplus was found to be stable without any separation or sedimentation with the stabilizer. The amount of drug retained was analyzed using HPLC and was found to be 89 ± 2.36 % (Figure 1e). Furthermore, the vaginal film was made using 20% PVA, 2% Glycerol as film loaded with MVC NS by using solvent casting method (Figure 2).

Conclusion: We anticipate that rapidly soluble film will saturate vaginal mucosa with MVC NS which will prevent HIV transmission after intercourse. Ultimately, it appears that the proposed MVC NS film may function as a potential delivery system for effective and biocompatible PrEP for HIV prevention.

Figure 1: (a) Schematic representation of preparation of Maraviroc nanosuspension (MVC NS), (b) Particle size of MVC NS with HPMC. (c) Particle size of MVC NS with Anionic Pullulan. (d) Particle size of MVC NS with Soluplus. (e) HPLC chromatogram of MVC NS with soluplus.

Figure 2: Schematic representation of developed MVC NS-loaded vaginal films.