Abstract
Amphiphilic copolymers of stearic acid (SA)-modified Bletilla striata polysaccharides (BSPs-SA) with three different degrees of substitution (DSs) were synthesized. The effects of DS values on the properties of BSPs-SA nanoparticles were evaluated. Drug state, cytotoxicity, and histological studies were carried out. The affinity ability of bovine serum albumin (BSA) and the BSPs-SA nanoparticles was also characterized utilizing ultraviolet and fluorescence spectroscopy. Besides, the bioavailability and tissue distribution of docetaxel (DTX)-loaded BSPs-SA nanoparticles were also assessed. The results demonstrated that the DS increase of the hydrophobic stearic acid segment increased the negative charge, encapsulation efficiency, and drug-loading capacity while decreasing the critical aggregation concentration value as well as the release rate of docetaxel from the nanoparticles. Docetaxel was encapsulated in nanoparticles at the small molecules or had an amorphous status. The inhibitory capability of DTX-loaded BSPs-SA nanoparticles against 4T1 tumor cells was superior to that of Duopafei®. The ultraviolet and fluorescence results exhibited a strong binding affinity between BSPs-SA nanoparticles and bovine serum albumin, but the conformation of bovine serum albumin was not altered. Additionally, the area under the concentration–time curve (AUC0–∞) of DTX-loaded BSPs-SA nanoparticles was about 1.42-fold higher compared with Duopafei® in tumor-bearing mice. Docetaxel levels of DTX-loaded BSPs-SA nanoparticles in some organs changed, and more docetaxel accumulated in the liver, spleen, and the tumor compared with Duopafei®. The experimental results provided a theoretical guidance for further applications of BSPs-SA conjugates as nanocarriers for delivering anticancer drugs.
Highlights
Polymeric self-assembled nanoparticles have been applied in drug delivery systems for several decades and have attracted massive attention in the pharmaceutical field [1,2,3,4]
The results demonstrated that the particle sizes and polydispersity index values of DTX-loaded Bletilla striata polysaccharides (BSPs)-SA nanoparticles decreased as the degrees of substitution (DSs) values of stearic acid increased
This may be the result of a tighter interaction between the hydrophobic stearic acid domains of the nanoparticle due to the increase of DS values, indicating the formation of more intensive hydrophobic cores [25]
Summary
Polymeric self-assembled nanoparticles have been applied in drug delivery systems for several decades and have attracted massive attention in the pharmaceutical field [1,2,3,4]. The hydrophilic shell can stabilize the nanoparticle drug delivery systems, avoid the clearance of nanoparticles by the reticular endothelial system, and facilitate the accumulation of drugs in tumor by enhanced permeability and retention effects [9]. Owing to these perfect properties, self-assembled nanoparticles can serve as promising chemotherapeutic carriers and exhibit great potential in improving cancer therapy [10,11]. Hydrophilic polysaccharides modified with hydrophobic segments have attracted great attention [14,15] Both can self-aggregate into nanoparticles in an aqueous environment. Water-soluble polysaccharides (e.g., chitosan, hyaluronic acid, and dextran) can be modified and display amphiphilic properties through grafting different kinds of hydrophobic moieties, which provide an alternative candidate for drug delivery systems [5]
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