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Lipid poly (ɛ-caprolactone) hybrid nanoparticles of 5-fluorouracil for sustained release and enhanced anticancer
Safiullah Khan1, Muhammad Naeem Aamir1, Asadullah Madni1
1Department of Pharmaceutics, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur 63100, Punjab, Pakistan.
Aims:
The present study aimed to develop and characterize poly (ɛ-caprolactone) (PCL) based lipid polymer hybrid nanoparticles for sustained delivery and in-vitro anti-cancer activity in MCF-7 and HeLa cells cancer cell line.
Materials And Methods:
The nanoprecipitation method was used for the development of 5-fluorouracil loaded lipid polymer hybrid nanoparticles (LPHNPs). The developed LPHNPs were characterized for physicochemical characteristics and the anti-cancer effect was evaluated in MCF-7 and HeLa cells.
Significant Findings:
Six formulations having fixed amount of drug and varied lipid, polymer and emulsifier concentrations were prepared. The particle size was in the range of 174 ± 4 to 267 ± 2.65 nm, entrapment efficiency (92.87 ± 0.594 to 94.13 ± 0.772%), negative zeta potential, optimum polydispersity index and spherical shape. FTIR analysis shows no chemical interaction among the formulation components, DSC analysis reveals the disappearance of 5-FU melting endotherm in the developed LPHNPs suggesting amorphization of 5-FU in the developed system, XRD analysis indicates successful encapsulation of the drug in the lipid polymer matrix. The in-vitro release shows a biphasic release pattern with an initial burst release followed by a sustained release profile for 72 h. The drug loaded LPHNPs exhibited a greater cytotoxic effect than 5-FU solution due to sustained release and increased cellular internalization. The acute toxicity study revealed the safety of the developed carrier system for potential delivery of chemotherapeutic agents.
Significance:
The developed LPHNPs of 5-fluorouracil will provide the sustained release behavior of 5-fluorouracil to maximize the therapeutic efficacy and minimize the dose related toxicity.
