Poly(1,2-glycerol carbonate) nanoparticles for delivery of hydrophilic therapeutics
Embargo Date
2025-05-24
OA Version
Citation
Abstract
Hydrophilic therapeutics, including a wide range of peptides, proteins and small molecule drugs, play a pivotal role in biomedicine. To overcome their unfavorable pharmacokinetics such as rapid clearance and poor permeability through lipid membranes, various delivery strategies based on liposomes, solid lipid nanoparticles, lipophilic prodrugs have been investigated. However, the toxicity associated with the systemic administration of these formulations limits their applications. Previously, we developed poly(1,2-glycerol carbonate) nanoparticles (PGC NPs) that readily entrap a hydrophobic small molecule drug and deliver it to peritoneal tumors post intraperitoneal injection. Here, we designed PGC NPs capable of loading hydrophilic drugs with high efficiency. The Cy5-BSA loaded NPs achieved a high encapsulation efficiency of 92.97% and drug loading of 3.55 wt%, with sustained release for one week. AntiPD1-loaded NPs reached ~100% encapsulation efficiency and released a substantial dose of antibodies by day 7. The secondary structure of polyclonal antibodies loaded in the NPs was not affected by the formulation process, as demonstrated by the characteristic peaks and valleys on the CD spectra. Minimal cytotoxicity to NIH/3T3 and MSTO-211H/Luc cells was observed after treatment with up to 1.5 mg/mL blank NPs over 24 hours, indicating biosafety of the NPs. Additionally, a promising assay was developed for assessing anti-PD1/PDL1 efficacy in vitro. Our findings suggest that PGC NPs loaded with hydrophilic drugs hold potential as safe and effective drug delivery systems.