Controlled anticancer 5-Fluorouracil release from functionalized 5-FU/PLGA/CaP coating on titanium implants: Characterization, in vitro drug delivery and cytotoxicity

Abstract

Work presents a novel approach for creating anticancer coatings on titanium implants using 5-Fluorouracil (5-FU) loaded in calcium phosphate which is encapsulated in poly(lactic-co-glycolic acid) (PLGA/CaP) for controllable drug release. Our method involves the hybrid ultrasound-assisted micro-arc oxidation (UMAOH) technique, which make use of an ultrasound as an additional means of energy input resulting in increased pore size, drug deposition, and layer-by-layer self-assembly of PLGA. The multilayer coatings exhibit amorphous-crystalline structure with dicalcium phosphate anhydrous (DCPA) and β-tricalcium phosphate (β-TCP) phases, Ca/P ratio of 0.3, surface roughness (Ra) of 2.3–3.5 µm, and thickness between 52–60 µm. Drug release kinetics revealed a burst release for 5FU/CaP in the initial 10–20 min and sustained release over 2–4 h. 5FU/PLGA/CaP displayed a smooth, sustained release over 5 days. Biocompatibility studies showed that extracts from drug-free CaP and CaP/PLGA samples were nontoxic to HeLa, NIH-3Т3, and MCF-7 cell lines (≥ 80 % cell viability) for 0.2–24 h. In contrast, extracts from drug-loaded carriers were cytotoxic to NIH-3T3 cells (> 60 % cell death). Notably, 5-FU impregnation in the CaP coting demonstrated varying cytotoxicity, with the following cell death order: 75 % HeLa > 68 % NIH-3Т3 > 59 % MCF-7. PLGA modification reduced cytotoxicity with the following cell death order: 61 % HeLa > 52 % NIH-3Т3 > 46 % MCF-7. This work presents a promising strategy for localized, controlled drug delivery 5FU/PLGA/CaP system, with reduced cytotoxicity compared to PLGA-free 5-FU/CaP coating, advancing implant-based cancer treatment.