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.