For these reasons, we chose PTX as the model chemotherapeutic age

For these reasons, we chose PTX as the model chemotherapeutic agent. Despite its potent anticancer activity, unfortunately limited by poor water solubility and toxic side effects, it has no great advantage in tumor targeting for drug delivery and cancer therapy [13]. A series of efforts has been directed to the development of alternative delivery systems for PTX. Poly(d,l-lactide) (PLA), a FDA-approved biodegradable

and non-cytotoxic material with a good track record in offering great potential for controlled Pim inhibitor release, has stood out and been extensively used in the formulation of NPs for biotechnology and drug delivery applications [14]. However, in aqueous solution, the drug-loaded PLA NPs presented poor dispersibility and colloidal stability; in addition, the PLA NPs were not amenable to rapid clearance from the circulation by the RES, immediately after their injection SYN-117 into the systemic circulation. A safe and effective way to answer this problem is to design long-circulating NPs with hydrophilic polymers. Polyethylene glycol (PEG), also

a FDA-approved polymer highly soluble in water, has been widely used as a long-circulating agent to improve the biocompatibility and increase the colloidal stability of NPs through steric hindrance, which was often incorporated in drug carriers for delivery to the human body, according to its resistance against opsonization, the process through which protein adsorption is enhanced to induce phagocytosis [15–17]. Thereby, methoxypolyethylene glycol-poly(d,l-lactide) (MPEG-PLA) diblock copolymers have been of great interest as a completely biocompatible material for drug delivery [18, 19]. Moreover, MPEG-PLA could make long circulation possible for pharmaceutical uses and opened new perspectives for controlled drug delivery in particular. In this paper, we present PtdIns(3,4)P2 a dialysis technique to direct

the self-assembly of PTX-loaded NPs using MPEG-PLA diblock copolymers and PLA, respectively. The hydrophobic polymeric core of the platform readily encapsulated the water-insoluble drug for systemic delivery. The physicochemical properties of the PTX-MPEG-PLA NPs were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), dynamic light scattering (DLS), static light scattering (SLS), transmission electron microscopy (TEM), and confocal laser scanning microscopy (CLSM). In vitro drug release profiles and cytotoxicity tests were also conducted. The PTX-PLA NPs were also prepared and characterized in the same way and used for comparison. Methods Materials PTX (purity grade > 90%) was purchased from Qilu Pharmaceutical Co., Ltd. (Shandong, China). PLA (50 kDa) and MPEG-PLA (10%) were provided by Daigang BIO Engineer Co., Ltd. (Shandong, China). A dialysis bag (Mw cutoff = 8,000 to 14,000 Da) was Tanespimycin manufacturer ordered from Greenbird Inc. (Shanghai, China). Double-distilled water was used throughout.

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