Alpha-fetoprotein mediated targeting of polymeric nanoparticles to treat solid tumors.

Background: Serious side effects caused by paclitaxel formulation, containing toxic solubilizer Cremophor® EL, and its nonspecific accumulation greatly limit clinical paclitaxel application. Aim: To design paclitaxel-loaded copolymer of lactic and glycolic acids nanoparticles decorated with alpha-fetoprotein third domain (rAFP3d-NP) to increase paclitaxel safety profile. Methods: rAFP3d-NP was obtained via carbodiimide technique. Results: The particles were characterized with high paclitaxel loading content of 5% and size of 280 nm. rAFP3d-NP revealed biphasic profile with 67% release of paclitaxel during 220 h. Increased area under the curveinf and mean residence time values after rAFP3d-NP administration confirmed prolonged blood circulation compared with paclitaxel. rAFP3d-NP demonstrated significant tumor growth inhibition at 4T1 and SKOV-3 models. Conclusion: rAFP3d-NP is a promising delivery system for paclitaxel and can be applied similarly for delivery of other hydrophobic drugs.

Development of novel PLGA nanoparticles with co-encapsulation of docetaxel and abiraterone acetate for a highly efficient delivery into tumor cells.

Co-encapsulation of abiraterone acetate (AbrA) and docetaxel (Dtx) in polymeric nanoparticles as novel prototypes for prostate cancer treatment combining hormonal and chemotherapy was designed. Nanoparticles (NPs) composed of poly(dl-lactide-co-glycolide) (PLGA) were prepared by single-emulsion solvent evaporation technique and characterized in terms of morphology with atomic force microscopy and transmission electron microscopy. HPLC method for simultaneous determination of AbrA and Dtx encapsulation efficacy was developed. Also differential scanning calorimetry and Fourier-transform infrared spectroscopy were provided. To study the effectiveness of cellular internalization and distribution of NPs with AbrA and Dtx co-encapsulation (NP-AbrA/Dtx), a fluorescence microscopy was utilized. NPs prepared had size 256.3 ±9.4 nm and zeta potential -18.4 ±1.4 mV. Encapsulation efficacy for AbrA was 68.7% and for Dtx was 74.3%. NPs were able to control the AbrA and Dtx release within 24 h. The mathematical model of drug release was performed. The results obtained from confocal microscopy showed the effective accumulation of the NP-AbrA/Dtx in the cytoplasm of cells. Synthesized NPs possessed satisfactory parameters and a biphasic release profile, proceeding by the Fick diffusion mechanism, which provide prolonged release of the drugs and maintenance of their concentration. It was shown that NPs loaded with AbrA and Dtx exhibited a high cytotoxic activity on the LNCaP cell line, similar to the combination of free drugs of AbrA and Dtx, but in contrast to the combination of substances, had a synergistic mechanism of action. Our findings support the potential use of developed NPs in further in vivo studies. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1150-1158, 2019.