Prostate cancer (PCa) is the most common male malignancy and the second leading cause of cancer death in Western industrialized countries . The PCa progression does not only mean distant metastases but also development of hormone independence of its cells .
Docetaxel (Dtx)-based regimen is recommended as optional treatment in patients with hormone-refractory metastatic PCa, showing effective on locally advanced PCa and increasing overall survival . Despite the recently reported promising outcome of Dtx, this drug is associated with systemic toxicity that limits the dose and duration of therapy, particularly in elderly patients. Adverse effects of Dtx treatment include hypersensitivity reactions, bone marrow suppression, cutaneous reactions, fluid retention, peripheral neuropathy, alopecia, cardiac disorders, and tiredness . Moreover, to facilitate its clinical use, the Dtx poor water solubility requires a specific solvent system, such as ethanol/Tween 80 solution, which causes hypersensitivity reaction, reduced uptake by tumor tissue and increased exposure to other body compartments .
Therefore, alternative Dtx formulations are needed and nanoparticles (NPs)-based drug delivery systems are of special interest in addressing the major side effects of anticancer drug.
Recently, a number of polymers have been investigated for formulating biodegradable Dtx-loaded NPs for cancer chemotherapy. The most widely used class of biocompatible and biodegradable polymers, approved by Food and Drug Administration (FDA), is that of aliphatic polyesters, including poly(lactic acid) (PLA), poly(glycolic acid) (PLGA), and their copolymers .
However, these polymers are characterized by a high hydrophobicity and slow degradation rate that can represent in some cases a disadvantage for their use as drug carriers .
In the family of polyesters, polycaprolactone (PCL) shows an excellent biocompatibility and rapid degradability, good miscibility with a variety of polymers and great permeability, which make it a suitable candidate for drug carrier .
The methods for the preparation of NPs from the preformed polymers include nanoprecipitation, emulsification/solvent evaporation, emulsification/solvent diffusion, and salting out . As for the nanoprecipitation, the particle formation is based on precipitation and subsequent solidification of the polymer at the interface between a solvent and a non-solvent . Usually, surfactants or stabilizers are included in the process to modify the size and the surface properties, and to ensure the stability of the NP dispersion . The most popular stabilizer for the production of PLGA-based NPs is poly(vinyl alcohol) (PVA). However, it has been found that residual PVA, which is very difficult to remove from the particles' surface, causes relatively lower cellular uptake, thus resulting not satisfactorily biocompatible for the human body . Therefore, other surfactants could be considered as valuable alternatives to PVA. Poloxamer, a block copolymer of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), commercially known as Pluronic, is another promising surface active agent approved by FDA for clinical use . Additionally, several evidence demonstrated that poloxamers interact with multidrug-resistant tumors, resulting in a drastic sensitization of these tumors with respect to various anticancer agents [13, 14].
The present work is aimed at investigating the influence of two previously unexplored biodegradable block-copolymers, such as poly(D,L-lactide-co-caprolactone) (PLA-PCL) and poly(L-lactide-co-caprolactone-co-glycolide) (PLGA-PCL), on the physicochemical and pharmaceutical properties of novel Dtx-loaded NPs, using PLA- and PLGA-NPs as comparison. The designed nanosystems were obtained by a modified nanoprecipitation technique, using Pluronic F-127 instead of PVA as stabilizing agent. The NPs were characterized in terms of morphology, encapsulation efficiency and crystalline structure, and in vitro release kinetics. Moreover, the antiproliferative efficacy of the most promising nanoparticulate prototype was assessed by in vitro cytotoxicity assay toward a human prostate cancer cell line (PC3).