Lipid poly (ɛ-caprolactone) hybrid nanoparticles of 5-fluorouracil for sustained release and enhanced anticancer efficacy

• Published in: Life sciences (1973) 2021-11, Vol.284, p.119909
• Main Authors: Khan, Safiullah, Aamir, Muhammad Naeem, Madni, Asadullah, Jan, Nasrullah, Khan, Arshad, Jabar, Abdul, Shah, Hassan, Rahim, Muhammad Abdur, Ali, Ahsan
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Acute toxicity; Amorphization; Anticancer properties; Antineoplastic Agents - pharmacology; Antitumor activity; Calorimetry, Differential Scanning; Cancer; Cell Survival - drug effects; Chemotherapy; Controlled release; Cytotoxicity; Delayed-Action Preparations - pharmacology; Drug Liberation; Entrapment; Fluorouracil - pharmacology; HeLa Cells; Humans; Internalization; Kinetics; Lipids; Lipids - chemistry; MCF-7 Cells; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Organ Size - drug effects; Particle Size; Polydispersity; Polyesters - chemistry; Polymers; Spectroscopy, Fourier Transform Infrared; Static Electricity; Sustained release; Toxicity; Toxicity Tests, Acute; X-Ray Diffraction; Zeta potential
• ISSN: 0024-3205; 1879-0631; 1879-0631
• DOI: 10.1016/j.lfs.2021.119909

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. 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. 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. 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.