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

Abstract

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 singleemulsion 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 Fouriertransform 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 AE9.4 nm and zeta potential −18.4 AE1.4 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.How to cite this article: Sokol MB, Nikolskaya ED, Yabbarov NG, Zenin VA, Faustova MR, Belov AV, Zhunina OA, Mollaev MD, Zabolotsky AI, Tereshchenko OG, Severin ES. 2019. Development of novel PLGA nanoparticles with co-encapsulation of docetaxel and abiraterone acetate for a highly efficient delivery into tumor cells. J Biomed Mater Res Part B 2019:107B:1150-1158.

Development and characterization of oxaceprol‐loaded poly‐lactide‐co‐glycolide nanoparticles for the treatment of osteoarthritis

“…In drug release studies, a biphasic release pattern was obtained from LNP, MNP and HNP formulations with an initial burst release, followed by a sustained release of remaining drug as seen in Figure . The initial burst release of oxaceprol from nanoparticles was due to both from molecules weekly bound to the surface of the nanoparticles and the diffusion of molecules located near to surface of nanoparticles (Sokol et al., ). Particularly, burst release was beneficial to obtain initial therapeutic concentration of OXC.…”

Polypeptide-Based Molecular Platform and Its Docetaxel/Sulfo-Cy5-Containing Conjugate for Targeted Delivery to Prostate Specific Membrane Antigen

“…The total number of synthesis steps (stages with chromatographic separation) 13 (10) 16 (7) In summary, the liquid-phase technique (Scheme 2) using method 2 (addition of the amine nucleophile to a solution of the coupling reagent and the acid only after they were reacted and generated an activated compound) to create a peptide bond between compound 10 and a vector fragment of ligand 6 was characterized by a maximum yield based on compound 11, but the minimum yield counting of the initial amino acid. The total number of stages using laborious chromatographic isolation was also large.…”

“…These compounds are composed of several functional units, one of which is an early diagnostic tool and the other is a therapeutic agent. This allows diagnosis and treatment of the disease simultaneously [8][9][10]. The advantage of this approach is the decrease in side effects and injection dose in order to improve diagnosis and treatment of the disease [11].…”

Improved Dissolution and Pharmacokinetics of Abiraterone through KinetiSol® Enabled Amorphous Solid Dispersions

“…Yonsa showed only a modest improvement, by doubling the bioavailability of abiraterone [14]. Other reported attempts to improve the bioavailability of abiraterone include the development of nanoamorphous formulations, lipid-based formulations, nanoparticles, and self-microemulsifying formulations [15][16][17][18][19][20]. Unfortunately, none of these attempts could yield the maximum therapeutic potential of abiraterone.…”