Albumin-Bound Betulinic Acid Nanoparticles to Enhance Bioavailability of Betulinic Acid
Parnali Chatterjee, College of Pharmacy and Health Sciences, Department of Pharmaceutical Sciences; Graduate Student: Yochana Srivari
Betulinic acid (BA), a pentacyclic triterpenoid, exhibits broad range of pharmacological activities including antiHIV, antimelanoma, antidiabetic, and antibacterial properties. It has received the RAID status from NCI. In a seminal study, at a dose of approximately 500 mg/kg (ip route in mouse), BA produced little or no observable toxicity. Despite selectivity towards melanoma cells, clinical development of BA has been slow due to poor aqueous solubility (0.02µg/mL in water). Low solubility can lead to low permeability and therefore poor bioavailability from orally administered dosage forms.
Objective: In order to improve the solubility of BA and target BA to cancerous cells, albumin-bound BA (Nab-BA) nanoparticles will be prepared and physico-chemical properties characterized.
Specific Aims: (1) Prepare albumin-bound BA nanoparticles. (2) Characterize the physico-chemical properties of albumin-bound BA nanoparticles including particle size and structure of albumin-bound BA using NMR and HRMS, as well as drug loading, albumin-binding kinetics of BA, and drug release from albumin.
Methods: Briefly, (1) Varying concentrations of BA was incubated with human serum albumin (HSA) at pH 7.0 and 8.0 for up to 24 hr at RT to prepare Nab-BA. (2) The particle size and morphology of Nab-BA was determined by SEM and TEM and the structure of Nab-BA will be confirmed by 1D- and 2D-NMR as well as HRMS. The binding kinetics of albumin to BA will be determined as well as drug release from albumin will be evaluated.