Amphiphilic Block Copolymer Poly (Acrylic Acid)-B-Polycaprolactone as a Novel pH-sensitive Nanocarrier for Anti-Cancer Drugs Delivery: In-vitro and In-vivo Evaluation

Abstract

Gambogenic acid (GNA) has been demonstrated with outstanding antitumor activity as a potential antitumor drug in recent years. However, the low solubility and deficient bioavailability of GNA seriously hinder its practical application in the clinic area. In this study, a novel amphiphilic block copolymer, poly (acrylic acid)-b-polycaprolactone (PAA-b-PCL) is prepared and assembled into pH-responsive polymeric micelles (PMs) as one mold of drug delivery system (DDS) with unique properties. Relevant investigation on PMs exhibits excellent carrying potential and pH-dependent release performance for GNA. The drug loading capacity (DLC) and drug loading efficiency (DLE) for GNA-loaded PMs can be achieved as high as 15.20 ± 0.07% and 83.67 ± 0.49%, respectively. The in vitro experiments indicate that the GNA releasing time, cytotoxicity, and cellular uptake are significantly enhanced. Especially, the peak concentration (Cmax) and area under the curve (AUC) are promoted sharply in the GNA-loaded PMs concentration-time curve. This study not only provides a novel way to widen the application of anticancer GNA in the future, but also extends the potential of stimuli-responsive copolymers to biomedical applications.

Polymeric micelles for the delivery of poorly soluble drugs: From nanoformulation to clinical approval

“…Endosomes and the tumor microenvironment where the local pH is slightly acidic are the targeted spaces for such pHsensitive polymers. Several pH-sensitive polymers have been employed in polymeric micelle formulations including polycations such as poly(histidine) [131], poly(4-vinylpyridine) [132], poly(N,N-dimethylaminoethylmethacrylate) [133], poly(β-amino ester) (PBAE) [134], and polyanions, such as poly(acrylic acid) [135], poly(methacrylic acid) (PMAA) [136], and poly(sulfonamides) [137].…”

Recent advances in the targeted delivery of paclitaxel nanomedicine for cancer therapy

“…The acidic microenvironment of the extracellular matrix of tumors, endosomes, and lysosomes vary. 75 The drug will be delivered outside or in cancer cells based on the susceptibility of the micelle to pH, producing various anti-tumor actions. Clinically, it has been observed that the side effects of anticancer agents on the healthy organs of patients and the drug resistance exhibited by tumor cells are the main reasons why chemotherapy is not as effective as it should be.…”

PCL-ZnO/TiO2/HAp Electrospun Composite Fibers with Applications in Tissue Engineering

“…The biodegradable materials [15,16] must support the processes of regeneration and repair of bone tissue, while providing mechanical support and, subsequently, degrading into non-toxic products, eventually being eliminated from the body. In the case of synthetic polymers, the most used in the field of hard tissue engineering are polycaprolactone, polylactic acid, polyglycolic acid, and polyethylene glycol [17,18,19,20,21].…”