Abstract 6903: PERMnano: A quick method to develop nanoliposomes and nanosuspensions for oral/parenteral administration to expedite preclinical testing

Abstract The vast majority of novel drug candidates are hydrophobic in nature, which often presents significant challenges in formulation due to poor aqueous solubility, limiting their drug delivery, systemic concentration, and availability at the target site. Generally, organic solvents (ethanol, PEG, DMSO etc.), cellulose polymers, vegetable oils and surfactants are used to administer drugs for preclinical testing. However, these methods may result in false negative efficacy and poor translational insight. Liposomes (a bilayer phospholipid vesicle) and nanosuspensions (nanostablized drug particles) have emerged as promising delivery systems to overcome these challenges with great translational potential. However, both technologies require a thorough knowledge of excipients, set-up, processing and skilled manpower. This study explores a simple and quick approach for preparing nanoliposomes and nanosuspension of various hydrophobic drugs for oral and parenteral administration. The first objective was to develop an excipient blend for the preparation of liposomes/nanosuspension based on the physicochemical properties of the drug and the route of administration. The second objective was to develop a rapid media milling process using parenterally acceptable zirconia beads. Thus, the study aimed to develop and optimize a premix excipient blend with rapid nanomilling for the preparation of nanomedicine (PERMnano). For liposomes, a pro-liposome powder was prepared through a modified solvent evaporation method, using three different saturated and unsaturated phospholipids, PEGylated DSPE and cholesterol. For nanosuspensions, stabilizer blends (FDA-approved stabilizers for oral and parenteral use) were prepared using a freeze-drying process. Various hydrophobic drugs, including Amphotericin B, Docetaxel, Ibrutinib, BRD4 PROTAC, Sotorasib, Mebendazole, Ebselen, and Irinotecan were suspended into aqueous phase with 1-10% premixed excipient blends for nanoliposomes and nanosuspension. The results demonstrated that both liposomes and nanosuspensions prepared via rapid wet media milling showed desirable physicochemical properties, with particle sizes consistently below 200 nm and with narrow size distribution (PDI < 0.2), indicating uniformity and stability. Entrapment efficiency (%EE) and drug loading (%DL) were significantly influenced by the choice of excipient blend and physicochemical properties of the drug candidate. The resultant formulations were stable and suitable for administration into animals. In conclusion, PERMnano could potentially provide a rapid, translational, and efficient technique for preclinical drug delivery of hydrophobic drug molecules, including beyond the rule of 5 molecules, high dose candidates and PROTACs. Citation Format: Henis Patel, Himaxi Patel, Akanksha Ugale, Ketan Patel. PERMnano: A quick method to develop nanoliposomes and nanosuspensions for oral/parenteral administration to expedite preclinical testing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6903.