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 deliver

Study of polymer-plasticizer interaction by <SUP>13</SUP>C CP/MAS NMR spectroscopy: poly(vinyl chloride)-bis (2-ethylhexyl) phthalate system

Solid state 13C CP/MAS studies of poly(vinyl chloride) (PVC)-bis(2-ethylhexyl) phthalate (DOP) have been carried out to elucidate the dynamics of polymer-plasticizer interaction at the molecular level. 13C NMR spectra, spin-lattice relaxation time T1(C) and spin-spin relaxation time T2(C) were obtained for various PVC-DOP samples. Line widths of &gt;CH - Cl show a sharp increase due to the strong hydrogen-bonding interaction between the &gt;C = O (ester) group of DOP and &gt;CHCl of PVC with various concentrations of DOP. The spin-lattice relaxation time T1(C) also confirms the presence of a strong interaction due to hydrogen bonding. The less mobile intermediate phase is mostly affected by the presence of plasticizer. The spin-spin relaxation time T2(C) shows that DOP is a mixed type plasticizer showing the features of both molecular and structural type plasticization

Poly(d,l‑lactide-<i>co</i>-glycolide) Surface-Anchored Biotin-Loaded Irinotecan Nanoparticles for Active Targeting of Colon Cancer

A poly(d,l-lactide-co-glycolide) (PLGA) copolymer was synthesized using the ring-opening polymerization of d,l-lactide and glycolide monomers in the presence of zinc proline complex in bulk through the green route and was well characterized using attenuated total reflectance–Fourier transform infrared, 1H and 13C nuclear magnetic resonance, gel permeation chromatography, differential scanning calorimetry, X-ray diffraction, matrix-assisted laser desorption/ionization time-of-flight, etc. Furthermore, PLGA-conjugated biotin (PLGA-B) was synthesized using the synthesized PLGA and was employed to fabricate nanoparticles for irinotecan (Ir) delivery. These nanoparticles (PLGA-NP-Ir and PLGA-B-NP-Ir) were tested for physicochemical and biological characteristics. PLGA-B-NP-Ir exhibited a stronger cellular uptake and anticancer activity as compared to PLGA-NP-Ir in CT-26 cancer cells (log p < 0.05). The accumulation and retention of fluorescence-labeled nanoparticles were observed to be better in CT-26-inoculated solid tumors in Balb/c mice. The PLGA-B-NP-Ir-treated group inhibited tumor growth significantly more (log p < 0.001) than the untreated control, PLGA-NP-Ir, and Ir-treated groups. Furthermore, no body weight loss, hematological, and blood biochemical tests demonstrated the nanocarriers’ nontoxic nature. This work presents the use of safe PLGA and the demonstration of a proof-of-concept of biotin surface attached PLGA nanoparticle-mediated active targeted Ir administration to combat colon cancer. To treat colon cancer, PLGA-B-NP-Ir performed better due to specific active tumor targeting and greater cellular uptake due to biotin