Polymeric complex micelles with double drug-loading strategies for folate-mediated paclitaxel delivery.

Drug loading is a key procedure in the preparation of drug-loaded nano-carriers. In this study, the paclitaxel (PTX)-loaded polymeric complex micelles (FA-P123-PTX/PTX micelles) with double drug-loading strategies were designed and prepared to improve the drug loading percentage of carriers and its anti-tumor efficiency. PTX was simultaneously conjugated to pluronic P123 (P123) polymer and encapsulated inside the P123 complex micelle. Folate (FA) was linked to the surface of micelles for the active target delivery of micelles to tumor cells. The FA-P123-PTX/PTX micelles showed spherical shaped with high drug loading of 18.08±0.64%. The results of cellular uptake studies suggested that FA could promote the internalization of micelles into the FR positive cells. FA-P123-PTX/PTX micelles showed significant higher anti-tumor activity against FR positive tumor cells compared to Taxol(®) (p<0.05). Moreover, the FA-P123-PTX/PTX micelles exhibited higher anti-tumor efficacy in B16 bearing mice with better safety property compared with Taxol(®). These results suggested that FA-P123-PTX/PTX micelles with double drug-loading strategies showed great potential for targeted delivery of anti-cancer drugs.

Li M ，Liu Y ，Feng L ，Liu F ，Zhang L ，Zhang N ... -  《-》

Paclitaxel-loaded Pluronic P123/F127 mixed polymeric micelles: formulation, optimization and in vitro characterization.

Wei Z ，Hao J ，Yuan S ，Li Y ，Juan W ，Sha X ，Fang X ... -  《-》

Dual targeting folate-conjugated hyaluronic acid polymeric micelles for paclitaxel delivery.

A series of novel self-assembled hyaluronic acid derivatives (HA-C(18)) grafted with hydrophobic octadecyl moiety and further dual targeting folic acid-conjugated HA-C(18) (FA-HA-C(18)) were synthesized. With the increase in the degree of substitution of octadecyl group from 12.7% to 19.3%, the critical micellar concentration of HA-C(18) copolymers decreased from 37.3 to 10.0 μg/mL. Paclitaxel (PTX) was successfully encapsulated into the hydrophobic cores of the HA-C(18) and FA-HA-C(18) micelles, with encapsulation efficiency as high as 97.3%. The physicochemical properties of the polymeric micelles were measured by DLS, TEM and DSC. Moreover, in vitro release behavior of PTX was investigated by dialysis bag method and PTX was released from micelles in a near zero-order sustained manner. In vitro antitumor activity tests suggested PTX-loaded HA-C(18) and FA-HA-C(18) micelles exhibited significantly higher cytotoxic activity against MCF-7 and A549 cells compared to Taxol at a lower PTX concentration. The cellular uptake experiments were conducted by quantitative assay of PTX cellular accumulation and confocal laser scanning microscopy imaging of coumarin-6 labeled HA-C(18) and FA-HA-C(18) micelles in folate receptor overexpressing MCF-7 cells. Folate and CD44 receptor competitive inhibition studies performed by fluorescence microscopy imaging suggested intracellular delivery of HA-C(18) and FA-HA-C(18) micelles were efficiently taken up via CD44 receptor-mediated endocytosis. The folate receptor-mediated endocytosis further enhanced internalized amounts of FA-HA-C(18) micelles in MCF-7 cells, as compared with HA-C(18) micelles. The internalization pathways of PTX-loaded HA-C(18) and FA-HA-C(18) micelles might include clathrin-mediated endocytosis, caveolae-mediated endocytosis and macropinocytosis. Therefore, the present study suggested that HA-C(18) and FA-HA-C(18) copolymers as biodegradable, biocompatible and cell-specific targetable nanostructure carriers, are promising nanosystems for cellular and intracellular targeting delivery of hydrophobic anticancer drugs.

Liu Y ，Sun J ，Cao W ，Yang J ，Lian H ，Li X ，Sun Y ，Wang Y ，Wang S ，He Z ... -  《-》

Pharmacokinetics and biodistribution of polymeric micelles of paclitaxel with Pluronic P123.

Han LM ，Guo J ，Zhang LJ ，Wang QS ，Fang XL ... -  《-》

In vivo pharmacokinetics, biodistribution and anti-tumor effect of paclitaxel-loaded targeted chitosan-based polymeric micelle.

Rezazadeh M ，Emami J ，Hasanzadeh F ，Sadeghi H ，Minaiyan M ，Mostafavi A ，Rostami M ，Lavasanifar A ... -  《-》