Green synthesis of methoxy-poly(ethylene glycol)-block-poly(l-lactide-co-glycolide) copolymer using zinc proline as a biocompatible initiator for irinotecan delivery to colon cancer in vivo.

Poly(lactic-co-glycolic acid) (PLGA) is the most commonly described biocompatible copolymer used in biomedical applications. In this work, a green synthetic approach based on the biocompatible zinc proline complex, as an initiator for PLGA synthesis, is reported for the first time for the synthesis of methoxy-poly(ethylene glycol)-block-poly(l-lactic-co-glycolic acid) (mPEG-PLGA). mPEG-PLGA with controlled molecular weight and narrow polydispersity was synthesised. Its potential for delivery of irinotecan (Ir), a poorly water-soluble chemotherapeutic drug used for the treatment of colon and pancreatic cancer, was studied. Nanoparticles of controlled size (140-160 nm), surface charge (∼-10 mV), release properties and cytotoxicity against CT-26 (colon) and BxPC-3 (pancreatic) cancer cells, were prepared. Tumor accumulation was confirmed by optical imaging of fluorescently labelled nanoparticles. Unlike Tween® 80 coated NP-Ir, the Pluronic® F-127 coated NP-Ir exhibits significant tumor growth delay compared to untreated and blank formulation treated groups in the CT-26 subcutaneous tumor model, after 4 treatments of 30 mg irinotecan per kg dose. Overall, this proof-of-concept study demonstrates that the newly synthesized copolymer, via a green route, is proven to be nontoxic, requires fewer purification steps and has potential applications in drug delivery.

Clopidogrel eluting electrospun polyurethane/polyethylene glycol thromboresistant, hemocompatible nanofibrous scaffolds.

Biomaterials used as blood-contacting material must be hemocompatible and exhibit lower thrombotic potential while maintaining hemostasis and angiogenesis. With the aim of developing thromboresistant, hemocompatible nanofibrous scaffolds, polyurethane/polyethylene glycol scaffolds incorporated with 1, 5, and 10 wt% Clopidogrel were fabricated and evaluated for their physiochemical properties, biocompatibility, hemocompatibility, and antithrombotic potential. The results of physicochemical characterization revealed the fabrication of nanometer-sized scaffolds with smooth surfaces. The incorporation of both polyethylene glycol and Clopidogrel to polyurethane enhanced the hydrophilicity and water uptake potential of polyurethane/polyethylene glycol/Clopidogrel scaffolds. The dynamic mechanical analysis revealed the enhancement in mechanical strength of the polyurethane/polyethylene glycol scaffolds on incorporation of Clopidogrel. The polyurethane/polyethylene glycol/Clopidogrel scaffolds showed a tri-phasic drug release pattern. The results of hemocompatibility assessment demonstrated the excellent blood compatibility of the polyurethane/polyethylene glycol/Clopidogrel scaffolds, with the developed scaffolds exhibiting lower hemolysis, increased albumin and plasma protein adsorption while reduction in fibrinogen adsorption. Further, the platelet adhesion was highly suppressed and significant increase in coagulation period was observed for Clopidogrel incorporated scaffolds. The results of cell adhesion and cell viability substantiate the biocompatibility of the developed nanofibrous scaffolds with the HUVEC cell viability on polyurethane/polyethylene glycol, polyurethane/polyethylene glycol/Clopidogrel-1, 5, and 10% at day 7 found to be 12.35, 13.36, 14.85, and 4.18% higher as compared to polyurethane scaffolds, and the NIH/3T3 cell viability found to be 35.27, 70.82, 36.60, and 7.95% higher as compared to polyurethane scaffolds, respectively. Altogether the results of the study advocate the incorporation of Clopidogrel to the polyurethane/polyethylene glycol blend in order to fabricate scaffolds with appropriate antithrombotic property, hemocompatibility, and cell proliferation capacity and thus, might be successfully used as antithrombotic material for biomedical application.