Orawan Suwantong

Aliphatic Lipid Substitution on 2 kDa Polyethylenimine Improves Plasmid Delivery and Transgene Expression

This study was conducted in order to develop amphiphilic, low molecular weight polymeric carriers for nonviral gene delivery. Caprylic, myristic, palmitic, stearic, oleic and linoleic acids were grafted onto the 2 kDa polyethylenimine (PEI) and properties critical for gene delivery were investigated using 293T and bone marrow stromal cells. The extent of lipid substitution on the polymers was controlled by the lipid:PEI feed ratio during the synthesis. The toxicity of the native and lipid-substituted 2 kDa PEI was relatively lower than the 25 kDa PEI, although lipid substitution generally increased the toxicity of the polymers in vitro. Lipid substitution reduced the ability of the polymers to complex DNA, as well as the stability of final complexes, as measured by heparin-induced dissociation. Once fully complexed to a plasmid DNA, however, the lipid-substituted polymers increased the plasmid DNA delivery to the cells. In 293T cells, the lipid-substituted polymers displayed a transfection ability that was equivalent to highly effective 25 kDa PEI, but without the toxic effect associated with the latter polymer. Among the lipids explored, no particular lipid emerged as the ideal substituent for transgene expression, although linoleic acid appeared to be superior to other lipid substituents. No correlation was evident between the level of substitution and DNA delivery efficiency of the polymers, and as little as 1 lipid substitution per PEI was effective in transforming the ineffective 2 kDa PEI into an effective carrier. The current structure-function studies are providing important clues about the properties critical for gene delivery and providing carriers effective for nonviral plasmid delivery.

Impact of Lipid Substitution on Assembly and Delivery of siRNA by Cationic Polymers

Characterization of a polymer library engineered to enhance their ability to protect and deliver their nucleotide cargo to the cells is reported. The ζ-potential continuously increased with higher polymer:siRNA weight ratio, and the ζ-potential of lipid-modified polymers:siRNA complexes were higher than PEI2 at all ratios. At polymer:siRNA ratio of 1:1, all lipid-substituted polymers showed complete protection against degradation. Lipid-modified polymers significantly increased the cellular uptake of siRNA complexes and down-regulation of GAPDH and P-gp (max. 66% and 67%, respectively). The results indicate that hydrophobic modification of low molecular PEI could render this otherwise ineffective polymer to a safe effective delivery system for intracellular siRNA delivery and protein silencing.

Electrospinning of Biocompatible Polymers and Their Potentials in Biomedical Applications

Electrospinning has been recognized as a versatile method for the fabrication of continuous ultrafine fibers using electrical forces. Various natural and synthetic polymers have been successfully electrospun into non-woven mats or oriented fibrous bundles with high porosity and large surface areas. Despite the numerous reports on the production of electrospun fibers, these fiber mats did not gain much interest for use in the biomedical field until the past decade. This review summarizes the research and development related to the electrospinning of some common biocompatible polymers as well as an overview of their potential in many biomedical applications such as tissue engineering, wound dressing, carriers for drug delivery or controlled release, and enzyme immobilization.

In vitro biological evaluation of electrospun cellulose acetate fiber mats containing asiaticoside or curcumin

Ultra-fine cellulose acetate (CA; M(w) approximately 30,000 Da; degree of acetyl substitution approximately 2.4) fiber mats containing either asiaticoside [from the plant Centella asiatica (L.); either in the form of a crude extract (CACE) or pure substance (PAC)] or curcumin (CM; from the plant Curcuma longa L.) were successfully prepared. The proposed use of these materials is as topical/transdermal patches or wound dressings. Here, the potential for use of these herb-loaded CA fiber mats as wound dressings was evaluated in terms of the stability and the antioxidant activity of the as-loaded herbal substances, the ability to support both the attachment and the proliferation of fibroblasts and the ability of the cultured fibroblasts to synthesize collagen. Normal human dermal fibroblasts (NHDF) were used as the reference fibroblastic cells. The results showed that the as-loaded herbal substances were stable even after the herb-loaded CA fiber mats had been aged either at room temperature or at 40 degrees C for a period of up to 4 months. The inclusion of asiaticoside [either 2% (w/w) CACE or 40% (w/w) PAC] rendered the resulting CA fiber mats their superiority in supporting the attachment, promoting the proliferation, and upregulating the production of collagen of the seeded and/or the cultured NHDF to the corresponding solvent-cast films and the neat CA fiber mats. On the other hand, the presence of CM imparted the antioxidant activity to the resulting CA fiber mats.

Applications of Cellulose Acetate Nanofiber Mats

Electrospinning is an efficient process for fabrication of polymeric ultrafine fibers with diameters ranging from sub-micrometer to nanometer. It involves the application of a strong electric field across a conductive capillary attaching to a polymer liquid-containing reservoir and a collector. The obtained ultrafine fibers exhibit several interesting characteristics, e.g., high surface area to mass or volume ratio, high porosity, vast possibilities for surface functionalization, etc. These unique characteristics make them used in various applications such as biomedical, pharmaceutical, and industrial applications, etc. Cellulose acetate, the acetate ester of cellulose, has been widely used as fibers. Recently, the electrospinning of cellulose acetate has been attracted due to its good thermal stability, chemical resistance, biocompatibility, biodegradability, etc. These properties render it suitable for use in various applications including tissue engineering, drug delivery system, wound dressing, separation membrane, etc. This chapter covers research related to electrospinning of cellulose acetate and the potential applications of cellulose acetate fibers.

Self-reinforced poly(lactic acid) nanocomposites with integrated bacterial cellulose and its surface modification

Abstract Bacterial cellulose (BC) nanofibers, with and without silane surface modification, were incorporated into self-reinforced poly(lactic acid) (SR-PLA) nanocomposites at 1 and 10 wt%. Disintegrated BC was combined with electrospun PLA fiber mats by film stacking and compression molding at 165 °C for 40 sec to obtain SR-PLA/BC hybrid films. The effect of nanocellulose addition and its surface modification on the structure, morphology, and properties of the resulting composites were investigated. It was found that BC was a highly effective reinforcement for SR-PLA nanocomposites, providing a noticeable increase in the film’s strength and modulus. Moreover, surface modification of BC was shown to further enhance the film performances due to an improved PLA/BC interfacial interaction. At an optimum BC content, these hybrid films also exhibited outstanding ductility and toughness. Water vapor barrier properties were also enhanced, especially when modified BC was integrated in the SR-PLA films. Graphical Abstract