Study on the preparation and activity of intelligent response poly(lactic-co-glycolic acid)-ss-polyethylene glycol copolymer micelles

Abstract

Amphiphilic polymer micellar carriers are the most commonly used nanocarriers for oral delivery of hydrophobic drugs because their hydrophilic shell can avoid the recognition of the reticuloendothelial system (RES), has excellent drug-carrying capacity, and protect the drug from inactivation in the gastrointestinal fluid. The polymer micelle shell can enter cancer cells by endocytosis, and autophagy in cells, degradation by lysosomal pathway, so as to release drugs, prolong the circulation time of drugs in vivo, and then achieve the effect of drug sustained release. In this study, the glutathione-responsive PLGA-ss-PEG loaded paclitaxel (PTX) micelles (PLGA-ss-PEG-PTX) were developed for anticancer therapy. With its long-term circulation and EPR (enhanced permeability and retention) effect, and the micelle had disulfide bond, which could be used as the recognition group of tumor microenvironment, so that the PLGA-ss-PEG-PTX could specifically accumulate at the tumor site, so as to produce better anti-tumor effect. The PLGA-ss-PEG-PTX was formulated by the emulsification method in this study. The drug loading was about 21.54%, the entrapment efficiency was about 94.2%, and the particle size range was about 90 nm with narrow particle size distribution. Cytotoxicity and embryonic toxicity experiments were carried out using mouse lung cancer cells (LLC) and zebrafish fertilized eggs. It was proved that the low concentration of blank micelles had little cytotoxicity, but high concentration of blank micelles had adverse effects on zebrafish embryonic development, resulting in embryonic malformation. The uptake of drugs by cancer cells was studied by a high connotation cell imaging analysis system. The experiments showed that the drug molecules encapsulated in micelles could achieve higher uptake by cells compared with free drug molecules. In addition, in the in vivo evaluation experiment of drugs, the PLGA-ss-PEG-PTX could significantly enhance the therapeutic effect of the PTX, improve its water solubility, and improve its oral bioavailability.

Recent Advances in Nanotechnology-Based Targeted Delivery Systems of Active Constituents in Natural Medicines for Cancer Treatment

“…[36,38,39]; (2) hydrophobic polymers, such as poly lactic-co-glycolic acid (PLGA), polycaprolactone (PCL), polylactic acid (PLA), etc. [36,[40][41][42]; (3) amphiphilic block copolymers, mainly including D-alphatocopheryl polyethylene glycol succinate (TPGS), Soluplus ® , and Pluronic ® (F127, F68, and P123) [13,[43][44][45][46][47][48][49]. The classification and structures of the aforementioned polymers are shown in Table 1.…”

“…Poly lactic-co-glycolic acid (PLGA) [35,41] Polycaprolactone (PCL) [42,53] Polylactic acid (PLA) [34,40] Amphiphilic block copolymers D-alpha-tocopheryl polyethylene glycol succinate (TPGS) [43,44] Soluplus ® [47] Pluronic ® (F127, F68, P123) [45,46,49,54] [ 34,40] Amphiphilic block copolymers D-alpha-tocopheryl polyethylene glycol succinate (TPGS)…”

“…Poly lactic-co-glycolic acid (PLGA) [35,41] Polycaprolactone (PCL) [42,53] Polylactic acid (PLA) [34,40] Amphiphilic block copolymers D-alpha-tocopheryl polyethylene glycol succinate (TPGS) [43,44] Soluplus ® [47] Pluronic ® (F127, F68, P123) [45,46,49,54] Molecules 2023, 28, 7767 6 of 34 particle size was 124.3 ± 6.4 nm and could remain stable even after 15 days stored at 4 °C. ADGloaded micelles had more outstanding anti-tumor ability and higher bioavailability compared to free ADG.…”

Smart PEG-Block-PLA/PLA Nanosystems: Impact of the Characteristics of the Polymer Blend on the Redox Responsiveness

“…Unlike temperature and pH-responsive systems, the production of redox-responsive systems often requires sophisticated chemical modification, notably the insertion of a reduction-sensitive linker such as the well-known disulfide bonds (-SS-). The disulfide bond insertion, either between two polymers [ 2 , 3 ], between the polymer and the drug [ 4 ] or in each repeating unit of a polymer [ 5 , 6 ], is time- and money-consuming. Indeed, during the synthesis of stimuli-responsive polymers, several purification and characterization steps are necessary to obtain a pure smart product.…”

Formulation and Characterization of Raloxifene loaded Biodegradable Polymeric Nanomicelles

“…RAL-loaded PLGA 50:50 nano-micelles were characterized by various parameters for instance, Particle size, particle size diameter, zeta potential, morphological characterization like, SEM, %drug loading and %entrapment efficiency, in-vitro RAL release profile. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]…”