Present studies are carried out with an aim to make degradable materials based on caprolactone and vinyl acetate units using radical chemistry. Radical ring-opening copolymerization of 2-methylene-1,3-dioxepane (MDO) with vinyl acetate in presence of AIBN initiator at 70 C was carried out to achieve the aim. The copolymerization introduced degradable PCL repeat units onto the C-C backbone of poly(vinyl acetate). Microstructure analysis of the copolymers is done using different 1D and 2D NMR techniques. Complete ring-opening polymerization of MDO to give ester units was observed during copolymerizations. Reactivity ratios were found out by Kelen Tüdos method and were r VAc ¼ 1:53 and r MDO ¼ 0:47 leading to statistical introduction of ester linkages onto the polymer backbone. The materials showed varied glass transition temperatures (from 37 to À44 C) depending upon the amount of ester linkages and very high elongations. The hydrolysis products were also tested for cytotoxicity studies in L929 cells and compared with that of known and accepted standard materials like poly(ethyleneimine). The hydrolysed products were non toxic and showed a cell viability > 95%. Keeping in view the combined properties like degradability, non-toxicity and low glass transition temperatures, the resulting materials could therefore be proposed for different applications like degradable gums, coatings etc.KEY WORDS: Radical Ring-Opening Polymerization / Polymer Synthesis / Degradable Polymers / Characterization / Ring-opening polymerization of "-caprolactone using anionic or metal catalysts is conventionally used for the synthesis of polycaprolactone (PCL), a well studied and in-demand degradable aliphatic polyester.1-7 A less known route to the formation of poly(caprolactone), first shown by Bailey et al. and later followed by some others, 9,10 is by radical ringopening polymerization of 2-methylene-1,3-dioxepane (MDO). 2-methylene-1,3-dioxepane is an interesting cyclic ketene acetal monomer giving poly("-caprolactone) (PCL), on the radical-ring-opening homopolymerization (RROP) and can introduce ester groups onto the vinyl polymer backbones during copolymerizations with vinyl monomers. The careful examination of 13C and 1 H NMR spectra by us 11 showed the occurrence of 100% ring-opening polymerization but the presence of about 9% branched structures in the resulting homopolymer obtained by RROP of MDO. This method of making ester linkages could be very well utilized for introducing degradability onto the nondegradable vinyl polymer backbones by copolymerizations. Also, the homopolymerization and copolymerization behaviour of different cyclic ketene acetals with some vinyl monomers like MMA, vinyl anisole, styrene etc. is reported by us 11-18 and others. 10,[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] The main problem during the copolymerization is the huge reactivity difference between the CKA and the vinyl monomers leading to either low molecular weight homo vinyl polymers without ester linkages or copolymers incorpor...

A potential siRNA carrier for pulmonary gene delivery was assessed by encapsulating siRNA into biodegradable polyester nanoparticles consisting of tertiary-amine-modified polyvinyl alcohol (PVA) backbones grafted to poly(d,l-lactide-co-glycolide) (PLGA). The resulting siRNA nanoparticles were prepared using a solvent displacement method that offers the advantage of forming small nanoparticles without using shear forces. The nanoparticles were characterized with regard to particle size, zeta-potential, and degradation at pH 7.4 using dynamic and static light scattering. SiRNA release studies were performed and correlated to the nanoparticle degradation. In vitro knockdown of firefly luciferase reporter gene was used to assess the potential of the nanoparticles as siRNA carriers in a human lung epithelial cell line, H1299 luc. The amine-modified-PVA-PLGA/siRNA nanoparticles form 150-200 nm particles with zeta-potentials of +15-+20 mV in phosphate buffered saline (PBS). Break down of the nanoparticles was seen within 4 h in PBS with sustained release of siRNA. These nanoparticles have achieved 80-90% knockdown of a luciferase reporter gene with only 5 pmol anti-luc siRNA, even after nebulization. Hence we conclude that amine-modified-PVA-PLGA/siRNA nanoparticles could be a promising siRNA carrier for pulmonary gene delivery due to their fast degradation and potent gene knockdown profile.

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We show that small and stable polyplex size achieved by pegylation is favourable for successful pulmonary gene delivery. Compared to PEI 25 kDa, pegylated PEI and CPP-PEG-PEI displayed enhanced transfection efficiency both in vitro and in vivo.

To introduce optical imaging among methods available to follow nanoparticle biodistribution, we have evaluated the concept of covalently labeling poly(lactide-co-glycolide) (PLGA) with a near-infrared (NIR) dye to obtain stable NIR fluorescent nanoparticles. PLGA was coupled with the NIR dye (DY-700, Dyomics) by an amide bond with 38% efficiency. Incorporating 1% of this conjugate into PLGA nanoparticles stabilised by polyvinyl alcohol (PVA) leads to stable nanoparticles (NPs) without affecting their colloidal characteristics (average diameter, polydispersity and zeta potential). In addition, nanoparticles remain strongly fluorescent and display good storage stability for 4 weeks at 4 C or over one week at 37 C. Nanoparticle cytotoxicity evaluated using HUVEC, NIH/3T3 and J774.A1 cell lines was similar for unlabeled or labeled NPs. Fluorescent nanoparticles and free dye were injected intravenously into mice and their biodistribution was followed for 24 h by NIR imaging, in vivo and ex vivo. Nanoparticles were found mainly in the liver whereas the free dye was not accumulating preferentially in this organ. The DY-700 NIR conjugate incorporated into PLGA NPs shows good performance both in vitro and in vivo, thus paving the way to finely traceable PLGA nanosystems for in vivo administration.