Development and Evaluation of Lyophilized Stealth liposomal Phyllanthin: Pharmacokinetics and Toxicological studies

Abstract Though phyllanthin has several medical applications, especially in cancer treatment, oral administration of the drug is hampered by poor water solubility ultimately leading to inadequate bioavailability. To overcome the challenges related to solubility and increase oral bioavailability, current research focuses to develop phyllanthin-loaded liposomes by thin-film hydration and followed lyophilization. Several variants of conventional and pegylated liposomes were developed and their physicochemical properties were evaluated by various parameters such as size, zeta potential, and encapsulation efficiency. The optimal formulations (PHL2 & PHL7) were evaluated further for safety and efficacy. The compatibility of phyllanthin with excipients in selected formulations has been established by FTIR, DSC-TGA, and X-Ray diffraction studies. Toxicity and pharmacokinetic studies were conducted on rats to establish the safety and efficacy of the selected liposomal formulations. A sustained drug release pattern and enhanced bioavailability have been achieved with the liposomal formulations. The results from the current study indicate that phyllanthin-loaded pegylated liposomes are safest and ensure the maximum circulation half-life (t1/2), MRT, and low elimination constant(Kel) compared to conventional liposomes and pure phyllanthin drugs. Thus pegylated liposomes can be used as a potential tool for oral administration of phyllanthin for chemotherapy.