Azita Haddadi

Abstract: Docetaxel is a highly potent anticancer agent being used in a wide spectrum of cancer types. There are important matters of concern regarding the drug’s pharmacokinetics related to the conventional formulation. Poly(lactide- co -glycolide) (PLGA) is a biocompatible/biodegradable polymer with variable physicochemical characteristics, and its application in human has been approved by the United States Food and Drug Administration. PLGA gives polymeric nanoparticles with unique drug delivery characteristics. The application of PLGA nanoparticles (NPs) as intravenous (IV) sustained-release delivery vehicles for docetaxel can favorably modify pharmacokinetics, biofate, and pharmacotherapy of the drug in cancer patients. Surface modification of PLGA NPs with poly(ethylene glycol) (PEG) can further enhance NPs’ long-circulating properties. Herein, an optimized fabrication approach has been used for the preparation of PLGA and PLGA–PEG NPs loaded with docetaxel for IV application. Both types of NP formulations demonstrated in vitro characteristics that were considered suitable for IV administration (with long-circulating sustained-release purposes). NP formulations were IV administered to an animal model, and docetaxel’s pharmacokinetic and biodistribution profiles were determined and compared between study groups. PLGA and PEGylated PLGA NPs were able to modify the pharmacokinetics and biodistribution of docetaxel. Accordingly, the mode of changes made to pharmacokinetics and biodistribution of docetaxel is attributed to the size and surface properties of NPs. NPs contributed to increased blood residence time of docetaxel fulfilling their role as long-circulating sustained-release drug delivery systems. Surface modification of NPs contributed to more pronounced docetaxel blood concentration, which confirms the role of PEG in conferring long-circulation properties to NPs. Keywords: poly(lactide-co-glycolide), poly(lactide-co-glycolide)–poly(ethylene glycol), polymeric nanoparticles, docetaxel, emulsification solvent evaporation, sustained release, pharmacokinetics, biodistribution

Curcumin is recognized as a potential chemotherapeutic agent against a variety of tumors. However, the clinical application of curcumin is hindered due to its poor water solubility and fast degradation. The objective of this study was to investigate amphiphilic block copolymer micelles of poly(ethylene oxide)-b-poly(epsilon-caprolactone) (PEO-PCL) as vehicles for the solubilization, stabilization, and controlled delivery of curcumin. Curcumin-loaded PEO-PCL micelles were prepared by a cosolvent evaporation technique. PEO-PCL micelles were able to solubilize curcumin effectively, protect the encapsulated curcumin from hydrolytical degradation in physiological matrix, and control the release of curcumin over a few days. The characteristics of resultant micelles were found to depend on the polymerization degrees of epsilon-caprolactone. Among different PEO-PCL micelles, PEO(5000)-PCL(24500) was the most efficient in solubilizing curcumin while PEO(5000)-PCL(13000) was the best carrier in reducing its release rate. PEO-PCL micelle-encapsulated curcumin retained its cytotoxicity in B16-F10, a mouse melanoma cell line, and SP-53, Mino, and JeKo-1 human mantle cell lymphoma cell lines. These results demonstrated the potential of PEO-PCL micelles as an injectable formulation for efficient solubilization, stabilization, and controlled delivery of curcumin.

Biodegradable polymeric materials are the most common carriers for use in drug delivery systems. With this trend, newer drug delivery systems using targeted and controlled release polymeric nanoparticles (NPs) are being developed to manipulate their navigation in complex in vivo environment. However, a clear understanding of the interactions between biological systems and these nanoparticulates is still unexplored. Different studies have been performed to correlate the physicochemical properties of polymeric NPs with the biological responses. Size and surface charge are the two fundamental physicochemical properties that provide a key direction to design an effective NP formulation. In this critical review, our goal is to provide a brief overview on the influences of size and surface charge of different polymeric NPs in vitro and to highlight the challenges involved with in vivo trials.