Pharmacokinetic Assessments of Ursolic Loaded-Dendrimer Complex

Abstract

Background: This study investigates the application of polyamidoamine (PAMAM) dendrimers as an innovative drug delivery approach for enhancing the pharmacokinetic profile of ursolic acid (UA), a pentacyclic triterpenoid with multifaceted therapeutic properties. UA, sourced from plants like Sanguisorba officinalis and Salvia officinalis, has been extensively studied for its pharmacological characteristics, including anti-inflammatory, antioxidant, and anti-diabetic properties, as recognized in Traditional Chinese Medicine (TCM). The clinical utility of UA is hampered by low bioavailability, which is attributed to its hydrophobic nature. To address this limitation, we explore the use of PAMAM dendrimers, known for their drug delivery potential. Methods: The UA-PAMAM G0 dendrimers were synthesized with varying molar ratios. Characterization included size analysis, PDI, and zeta potential determination. FTIR confirmed the chemical structure. Male Wistar rats were acclimatized and administered UA control suspension and UA-G0 dendrimer complex orally. Blood samples were collected for pharmacokinetic analysis. The study obtained IAEC approval. Results: The UA-PAMAM G0 dendrimer complexes exhibited varying sizes based on molar ratios, with the 2:1 ratio showing significantly smaller dimensions. FTIR confirmed successful conjugation. In the pharmacokinetic study, the UA-G0 dendrimer complex demonstrated higher plasma concentrations than UA alone, as indicated by increased Cmax and AUC values. The results suggest enhanced oral delivery and bioavailability of UA in the dendrimer complex. Conclusion: This study demonstrated the successful synthesis of UA-PAMAM G0 dendrimer complexes with size variations based on molar ratios. The pharmacokinetic analysis revealed improved plasma concentrations and bioavailability of UA in the dendrimer complex compared to UA alone. These findings highlight the potential of PAMAM dendrimers for enhancing the oral delivery of hydrophobic compounds like UA, bridging the gap between traditional herbal medicine and modern drug delivery strategies. Further research can explore the broader applications of such dendrimer complexes in drug delivery systems.