One of major challenges in the drug delivery lies in the development of nanoparticles that are effectively delivered to targeted cells and release their payload over an extended period to achieve a clinical response. In this paper, we report a new family of biocompatible and biodegradable polymer, termed polyoxalate that degrades hydrolytically into nontoxic byproducts. Polyoxalate was synthesized from a simple one-step polymerization reaction of 1,4-cyclohexanedimethanol and oxalyl chloride and had a MW of approximately 11000 Da. This polymer was designed to degrade by water hydrolysis into 1,4-cyclohexanedimethanol and oxalic acid, which can be easily removed from a body. Polyoxalate had a hydrophobic backbone and was formulated into nanoparticles with a mean diameter of 600 nm, which is suitable for drug delivery involving phagocytosis by macrophages. Polyoxalate nanoparticles were readily taken up by RAW 264.7 macrophage cells and HEK (human embryonic kidney) 293 cells and exhibited a minimal cytotoxicity in a time- and dose-dependent manner. In comparison with PLGA nanoparticles, polyoxalate nanoparticles had a significantly higher cell viability. We anticipated that the ease of synthesis and excellent biocompatibility make polyoxalate highly potent for numerous applications in drug delivery.

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Drug delivery using biodegradable polymeric microparticles is becoming an important means of delivering therapeutic agents. In this work, we describe polyoxalate microparticles as a biodegradable and biocompatible protein drug-delivery system. Polyoxalate was synthesized from a polycondensation reaction between oxalyl chloride and 1,4-cyclohexanedimethanol under basic conditions. Polyoxalate, in design, undergoes hydrolytic degradation to generate non-toxic low-molecular-weight compounds that can be easily excreted from a body. Polyoxalate was hydrophobic and had a half-life of 6.5 days at pH 7.4. This hydrophobic polyoxalate could be formulated into microparticles by a double emulsion method and encapsulate proteins with a loading efficiency of more than 80%. Cytotoxicity evaluation using RAW 264.7 cells indicated that polyoxalate microparticles exhibited a cytotoxicity profile superior to PLGA microparticles. The polyoxalate microparticles were taken up by macrophages in vitro as confirmed by confocal fluorescence microscopy. The ease of synthesis coupled with the physicochemical properties and excellent biocompatibility make this polyoxalate a promising candidate for protein-delivery applications.

The retinal pigment epithelium (RPE) closely interacts with photoreceptors in the maintenance of visual function. The native RPEs exist as a monolayer structure and have a mottled brown color due to the presence of melanin and other pigments including lipofuscin granules, which accumulate with age. In age-related macular degeneration (AMD), RPE's dysfunction and changes in Bruch's membrane occur. Thus, small intestine submucosa/poly(lactic-co-glycolic acid) (SIS/PLGA) film is a biomimetic transplant consisting of a layer of healthy RPE cells cultured on a support membrane. The goals of this study were to evaluate the effects of attachment and proliferation of RPEs on SIS/PLGA films. Porcine SIS is an acellular tissue and widely used as a biomaterial without immunorejection responses, whereas PLGA is a biodegradable synthetic polymer with acceptable mechanical strength and well-controlled degradation rate. We fabricated SIS/PLGA films using 20 wt% of SIS. We measured MTT to confirm cellular adhesion of cell number attached on film at 1, 3, 5, and 7 days. Morphology of cellular adhesion on films was confirmed by scanning electron microscopy at 1, 3, and 7 days. Further, reverse transcription polymerase chain reaction (RT-PCR) was conducted to confirm messenger RNA expression of RPE65 as RPE's marker and expression of cytokeratin, and RPE65 were determined by AEC immunocytochemical staining. These results suggest that SIS provides suitable surface to RPEs.