ABSTRACT
The development of biodegradable and biocompatible materials is the basis for tissue engineering and drug delivery. The aims of this study are to develop the poly(oxalate-co-oxamide) (POXAM) and evaluate its physicochemical properties and biocompatibility as the initial step for the development of new biomaterials. POXAM had a molecular weight of ~70,000 Da and rapidly degraded under physiological condition with a half-hydrolysis of ~4 days. POXAM films exhibited relative hydrophilic nature because of the presence of oxamide linkages and induced a higher cell attachment and proliferation compared with poly(lactic-co-glycolic acid) (PLGA) films. In vitro inflammatory responses to POXAM were evaluated using murine macrophage RAW 264.7 cells. POXAM films minimally stimulated the cells to generate less production of tumor necrosis factor-alpha (TNF-α) than PLGA films. We assessed the in vivo inflammatory responses to POXAM films implanted in the dorsal skin of rats. Histological studies revealed that POXAM provoked remarkably reduced inflammatory responses, evidenced by the less accumulation of inflammatory cells and giant cells, thinner fibrotic capsules, in comparison with PLGA. Given its excellent biocompatibility, fast degradation, and very mild inflammatory responses, POXAM has great potential for biomedical applications, such as scaffolds, wound dressing, and fast drug delivery.
Subject(s)
Biocompatible Materials/chemistry , Biocompatible Materials/metabolism , Oxalates/chemistry , Oxalates/metabolism , Oxamic Acid/analogs & derivatives , Animals , Cell Line , Implants, Experimental , Lactic Acid/chemistry , Lactic Acid/metabolism , Macrophages/cytology , Macrophages/immunology , Materials Testing , Mice , Molecular Structure , Oxamic Acid/chemistry , Oxamic Acid/metabolism , Polyglycolic Acid/chemistry , Polyglycolic Acid/metabolism , Polylactic Acid-Polyglycolic Acid Copolymer , Rats , Rats, WistarABSTRACT
The large production of reactive oxygen species (ROS) leads to the oxidative stress and the subsequent functional decline of organ systems. p-Hydroxybenzyl alcohol (HBA) is known to play a pivotal protective role against oxidative stress-related diseases. We have developed biodegradable antioxidant copolyoxalate, in which HBA is chemically incorporated into its backbone for the treatment of oxidative stress-related diseases. HBA-incorporated copolyoxalate (HPOX) was designed to possess aromatic peroxalate ester linkages in its backbone and release HBA during its hydrolytic degradation. Peroxalate ester linkages in the backbone reacted with and scavenged hydrogen peroxide, leading the release of HBA in vitro. HBA released from HPOX exerted excellent antioxidant activity, such as inhibition of nitric oxide (NO) production by suppressing iNOS (inducible nitric oxide synthases) expression in lipopolysaccharide (LPS)-activated RAW 264.7 cells. HPOX nanoparticles delivered intranasally significantly reduced pulmonary inflammation and suppressed the iNOS expression. Given their excellent antioxidant and anti-inflammatory activities, we anticipate that HPOX nanoparticles are highly potent for the treatment of oxidative damage-related diseases, such as asthma.
Subject(s)
Antioxidants/chemistry , Antioxidants/pharmacology , Benzyl Alcohols/chemistry , Benzyl Alcohols/pharmacology , Nanoparticles/chemistry , Oxidative Stress/drug effects , Polymers/chemistry , Polymers/pharmacology , Animals , Hydrogen Peroxide/metabolism , Mice , Mice, Inbred BALB C , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolismABSTRACT
p-Hydroxybenzyl alcohol (HBA) is one of phenolic compounds in herbal agents and plays a pivotal role in protection against oxidative damage-related diseases due to anti-inflammatory effects. We have developed a new biodegradable and anti-inflammatory peroxalate copolymer in which HBA is chemically incorporated into its backbone. The HBA-incorporated copolyoxalate (HPOX) was synthesized from a condensation reaction of oxalyl chloride, 1,4-cyclohexamethanol and HBA and was capable of releasing pharmaceutically active HBA during hydrolytic degradation. HPOX could be dispersed into a single emulsion for the formulation of nanoparticles which had a mean size approximately 500 nm in diameter. The nanoparticles released HBA which was able to inhibit the production of nitric oxide (NO) by suppressing the expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophage cells. HPOX nanoparticles also reduced the production of tumor necrosis factor-alpha (TNF-alpha). The remarkable features of HPOX are that the polymer degrades completely into small molecules and one of degradation products is a pharmaceutically active compound. We anticipate that HPOX is highly potent and versatile for the treatment of inflammatory diseases.
