Nanonet-nano fiber electrospun mesh of PCL-chitosan for controlled and extended release of diclofenac sodium.

Electrospun nanofiber (EN) technology has been used in the past to generate electrostatically charged multilayer-nanofibers. This platform offers versatile applications including in tissue engineering, drug delivery, wound dressings, and high-efficiency particulate air filters. In this study, we synthesized for the first time nanonet-nanofiber electrospun meshes (NNEMs) of polycaprolactone (PCL)-chitosan (CH) using EN technology. The fabricated NNEMs were utilized for high payload delivery and controlled release of a water-soluble drug. Diclofenac Sodium (DS), a hydrophilic anti-inflammatory drug, was selected as a model drug because of its high aqueous solubility and poor compatibility with insoluble polymers. Various compositions of DS drug-loaded NNEMs (DS-NNEMs) were synthesized. The physicochemical properties such as structure, morphology, and aqueous stability and the chemical properties of DS-NNEMs were evaluated. High drug entrapment efficiency and concentration-dependent drug release patterns were investigated for up to 14 days. Furthermore, the biocompatibility of the DS-NNEMs was tested with NIH 3T3 cells. The physicochemical characterization results showed that the DS drug is a key contributing factor in the generation of nanonet-nanofiber networks during electrospinning. DS-NNEMs also enhanced 3T3 cell adhesion, viability, and proliferation in the nanonet-nano fiber network through the controlled release of DS. The presented EN technology-based biodegradable NNEM material is not only limited for the controlled release of hydrophilic anti-inflammatory drugs, but also can be a suitable platform for loading and release of antiviral drugs.

Embedding magnesium metallic particles in polycaprolactone nanofiber mesh improves applicability for biomedical applications.

Magnesium (Mg) metal is of great interest in biomedical applications, especially in tissue engineering. Mg exhibits excellent in vivo biocompatibility, biodegradability and, during degradation, releases Mg ions (Mg2+) with the potential to improve tissue repair. We used electrospinning technology to incorporate Mg particles into nanofibers. Various ratios of Mg metal microparticles (<44 µm diameter) were incorporated into nanofiber polycaprolactone (PCL) meshes. Physicochemical properties of the meshes were analyzed by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), mechanical tensile testing, X-ray diffractometry and UV-VIS spectrophotometry. Biological properties of meshes were evaluated in vitro and in vivo. Under mammalian cell culture conditions, Mg-containing meshes released hydrogen gas and relative amounts of free Mg2+ that reflected the Mg/PCL ratios. All meshes were non-cytotoxic for 3T3 fibroblasts and PC-12 pheochromocytoma cells. In vivo implantation under the skin of mice for 3, 8 and 28 days showed that Mg-containing meshes were well vascularized, with improved measures of inflammation and healing compared to meshes without Mg. Evidence included an earlier appearance and infiltration of tissue repairing macrophages and, after 28 days, evidence of more mature tissue remodeling. Thus, these new composite nanofiber meshes have promising material properties that mitigated inflammatory tissue responses to PCL alone and improved tissue healing, thus providing a suitable matrix for use in clinically relevant tissue engineering applications. STATEMENT OF SIGNIFICANCE: The biodegradable metal, magnesium, safely biodegrades in the body, releasing beneficial byproducts. To improve tissue delivery, magnesium metal particles were incorporated into electrospun nanofiber meshes composed of a biodegradable, biocompatible polymer, polycaprolactone (PCL). Magnesium addition, at several concentrations, did not alter PCL chemistry, but did alter physical properties. Under cell culture conditions, meshes released magnesium ions and hydrogen gas and were not cytotoxic for two cell types. After implantation in mice, the mesh with magnesium resulted in earlier appearance of M2-like, reparative macrophages and improved tissue healing versus mesh alone. This is in agreement with other studies showing beneficial effects of magnesium metal and provides a new type of scaffold material that will be useful in clinically relevant tissue engineering applications.

pH-Responsive PLGA Nanoparticle for Controlled Payload Delivery of Diclofenac Sodium.

Poly(lactic-co-glycolic acid) (PLGA) based nanoparticles have gained increasing attention in delivery applications due to their capability for controlled drug release characteristics, biocompatibility, and tunable mechanical, as well as degradation, properties. However, thorough study is always required while evaluating potential toxicity of the particles from dose dumping, inconsistent release and drug-polymer interactions. In this research, we developed PLGA nanoparticles modified by chitosan (CS), a cationic and pH responsive polysaccharide that bears repetitive amine groups in its backbone. We used a model drug, diclofenac sodium (DS), a nonsteroidal anti-inflammatory drug (NSAID), to study the drug loading and release characteristics. PLGA nanoparticles were synthesized by double-emulsion solvent evaporation technique. The nanoparticles were evaluated based on their particle size, surface charge, entrapment efficacy, and effect of pH in drug release profile. About 390-420 nm of average diameters and uniform morphology of the particles were confirmed by scanning electron microscope (SEM) imaging and dynamic light scattering (DLS) measurement. Chitosan coating over PLGA surface was confirmed by FTIR and DLS. Drug entrapment efficacy was up to 52%. Chitosan coated PLGA showed a pH responsive drug release in in vitro. The release was about 45% more at pH 5.5 than at pH 7.4. The results of our study indicated the development of chitosan coating over PLGA nanoparticle for pH dependent controlled release DS drug for therapeutic applications.

Magnesium incorporated chitosan based scaffolds for tissue engineering applications.

Chitosan based porous scaffolds are of great interest in biomedical applications especially in tissue engineering because of their excellent biocompatibility in vivo, controllable degradation rate and tailorable mechanical properties. This paper presents a study of the fabrication and characterization of bioactive scaffolds made of chitosan (CS), carboxymethyl chitosan (CMC) and magnesium gluconate (MgG). Scaffolds were fabricated by subsequent freezing-induced phase separation and lyophilization of polyelectrolyte complexes of CS, CMC and MgG. The scaffolds possess uniform porosity with highly interconnected pores of 50-250 µm size range. Compressive strengths up to 400 kPa, and elastic moduli up to 5 MPa were obtained. The scaffolds were found to remain intact, retaining their original three-dimensional frameworks while testing in in-vitro conditions. These scaffolds exhibited no cytotoxicity to 3T3 fibroblast and osteoblast cells. These observations demonstrate the efficacy of this new approach to preparing scaffold materials suitable for tissue engineering applications.

Fabrication and Characterization of Electrospun PCL-MgO-Keratin-Based Composite Nanofibers for Biomedical Applications.

Polymeric nanofibers are of great interest in biomedical applications, such as tissue engineering, drug delivery and wound healing, due to their ability to mimic and restore the function of natural extracellular matrix (ECM) found in tissues. Electrospinning has been heavily used to fabricate nanofibers because of its reliability and effectiveness. In our research, we fabricated poly(ε-caprolactone)-(PCL), magnesium oxide-(MgO) and keratin (K)-based composite nanofibers by electrospinning a blend solution of PCL, MgO and/or K. The electrospun nanofibers were analyzed by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), mechanical tensile testing and inductively-coupled plasma optical emission spectroscopy (ICP-OES). Nanofibers with diameters in the range of 0.2-2.2 µm were produced by using different ratios of PCL/MgO and PCL-K/MgO. These fibers showed a uniform morphology with suitable mechanical properties; ultimate tensile strength up to 3 MPa and Young's modulus 10 MPa. The structural integrity of nanofiber mats was retained in aqueous and phosphate buffer saline (PBS) medium. This study provides a new composite material with structural and material properties suitable for potential application in tissue engineering.