New Method to Prepare Mitomycin C Loaded PLA-Nanoparticles with High Drug Entrapment Efficiency

Abstract

The classical utilized double emulsion solvent diffusion technique for encapsulating water soluble Mitomycin C (MMC) in PLA nanoparticles suffers from low encapsulation efficiency because of the drug rapid partitioning to the external aqueous phase. In this paper, MMC loaded PLA nanoparticles were prepared by a new single emulsion solvent evaporation method, in which soybean phosphatidylcholine (SPC) was employed to improve the liposolubility of MMC by formation of MMC–SPC complex. Four main influential factors based on the results of a single-factor test, namely, PLA molecular weight, ratio of PLA to SPC (wt/wt) and MMC to SPC (wt/wt), volume ratio of oil phase to water phase, were evaluated using an orthogonal design with respect to drug entrapment efficiency. The drug release study was performed in pH 7.2 PBS at 37 °C with drug analysis using UV/vis spectrometer at 365 nm. MMC–PLA particles prepared by classical method were used as comparison. The formulated MMC–SPC–PLA nanoparticles under optimized condition are found to be relatively uniform in size (594 nm) with up to 94.8% of drug entrapment efficiency compared to 6.44 μm of PLA–MMC microparticles with 34.5% of drug entrapment efficiency. The release of MMC shows biphasic with an initial burst effect, followed by a cumulated drug release over 30 days is 50.17% for PLA–MMC–SPC nanoparticles, and 74.1% for PLA–MMC particles. The IR analysis of MMC–SPC complex shows that their high liposolubility may be attributed to some weak physical interaction between MMC and SPC during the formation of the complex. It is concluded that the new method is advantageous in terms of smaller size, lower size distribution, higher encapsulation yield, and longer sustained drug release in comparison to classical method.

Enhanced antifungal effects of amphotericin B-TPGS-b-(PCL-ran-PGA) nanoparticles in vitro and in vivo

“…The bulky structure and large surface area of AMB-NPs make them an excellent solubilizer, emulsifier, and bioavailable enhancer of hydrophobic drugs. 19,28 The NPs have high affinity to cells and can be rapidly internalized by these cells, and then AMB is gradually released from NPs in a sustained manner. 29 Our results suggested that PLGA-TPGS NPs were an excellent polymer carrier of hydrophobic drugs.…”

Cytotoxicity of a Novel Oil/Water Microemulsion System Loaded with Mitomycin‐C in In Vitro Lung Cancer Models

“…In order to overcome these side effects of MMC, and to obtain higher treatment efficacy, many attempts have been made to incorporate the drug in different delivery systems. These include intratumoral injection of MMC–dextran conjugates [Nomura et al., ], arterial chemoembolization with polyvinylalcohol or degradable starch microspheres [Rump et al., ; Shitara et al., ], and incorporation of MMC in polylactic acid nanoparticles [Hou et al., ].…”

Nanofibers by Green Electrospinning of Aqueous Suspensions of Biodegradable Block Copolyesters for Applications in Medicine, Pharmacy and Agriculture

“…Aqueous suspensions of biodegradable polyesters, e.g., PLA nanoparticles, are well known. [27,28] Suspensions of PLA nanoparticles are obtained as secondary suspensions, for example, by solvent displacement methods and emulsion, double emulsion and salting out methods. [29,30] The method selected is dependent on the size and loading efficiency required for different biomedical applications.…”