PCL-TPGS polymeric nanoparticles for docetaxel delivery to prostate cancer: Development, physicochemical and biological characterization

Author(s)

Raspantini, Giovanni Loureiro ^[1] ; Luiz, Marcela Tavares ^[1] ; Abriata, Juliana Palma ^[1] ; Eloy, Josimar de Oliveira ^[2] ; Vaidergorn, Miguel Menezes ^[1] ; da Silva Emery, Flavio ^[1] ; Marchetti, Juliana Maldonado ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, BR-14040900 Ribeirao Preto, SP - Brazil

^[2] Univ Fed Ceara, Fac Pharm Dent & Nursing, Dept Pharm, Fortaleza, Ceara - Brazil

• Document type: Journal article
• Source: COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS; v. 627, OCT 20 2021.
• Web of Science Citations: 0

Abstract

Prostate cancer is the second most common type of cancer in men, remaining the second leading cause of cancerrelated deaths in this gender. In order to improve the security and efficacy of its treatment, nanostructured delivery systems have been widely studied. The present work aimed to develop and characterize polymeric nanoparticles based on a copolymer of polycaprolactone-DL-alpha-tocopherol-polyethylene glycol-1000 (PCL-block-TPGS) containing docetaxel (PN-DTX) for prostate cancer therapy. TPGS was used in nanoparticle composition due to its ability to inhibit the P-glycopmtein, an efflux pump related with multidrug resistance. PCL-block-TPGS PN-DTX were obtained by the nanoprecipitation technique and characterized by their physicochemical, morphological and biological characteristics in vitro and in vivo. The systems were successfully obtained and had suitable size distribution, polydispersity index, zeta potential encapsulation efficiency and loading capacity for the proposed objectives (130 +/- 18 nm, 0.10 +/- 0.04, -30.1 +/- 2.3 mV, 96.2 +/- 1.1% and 5.01 +/- 0.32%, respectively). The encapsulation efficiency was confirmed by calorimetric and spectroscopic studies. Biological assays demonstrated the high ability of PN-DTX to cause cell death and to be internalized in PC-3 cell line, reaching EC50 of 0.476 +/- 0.092 nM and internalization of 97.64 +/- 1.21%. In vivo studies demonstrated efficacy of the system developed in an animal model with a reduction of tumor volume in 40.1% and 18.0% when compared with control and DTX commercial formulation groups, respectively. Therefore, docetaxel-loaded PCL-block-TPGS polymeric nanoparticle is a potential system for prostate cancer treatment. (AU)

• FAPESP's process: 16/03013-4 - e-polycaprolactone and D-±-tocopherol polyethylene glycol-1000 nanoparticles containing docetaxel aiming prostate cancer therapy
• Grantee: Giovanni Loureiro Raspantini
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 17/04091-1 - Development and characterization of delivery systems containing docetaxel for optimization of prostate cancer therapy: imunoliposomes and polymeric nanoparticles
• Grantee: Juliana Maldonado Marchetti
• Support Opportunities: Regular Research Grants