Co-delivery of drugs and DNA from cationic core-shell nanoparticles self-assembled from a biodegradable copolymer.
ABSTRACT Non-viral gene-delivery systems are safer to use and easier to produce than viral vectors, but their comparatively low transfection efficiency has limited their applications. Co-delivery of drugs and DNA has been proposed to enhance gene expression or to achieve the synergistic/combined effect of drug and gene therapies. Attempts have been made to deliver drugs and DNA simultaneously using liposomes. Here we report cationic core-shell nanoparticles that were self-assembled from a biodegradable amphiphilic copolymer. These nanoparticles offer advantages over liposomes, as they are easier to fabricate, and are more readily subject to modulation of their size and degree of positive charge. More importantly, they achieve high gene-transfection efficiency and the possibility of co-delivering drugs and genes to the same cells. Enhanced gene transfection with the co-delivery of paclitaxel has been demonstrated by in vitro and in vivo studies. In particular, the co-delivery of paclitaxel with an interleukin-12-encoded plasmid using these nanoparticles suppressed cancer growth more efficiently than the delivery of either paclitaxel or the plasmid in a 4T1 mouse breast cancer model. Moreover, the co-delivery of paclitaxel with Bcl-2-targeted small interfering RNA (siRNA) increased cytotoxicity in MDA-MB-231 human breast cancer cells.
SourceAvailable from: Pradeep Kumar[Show abstract] [Hide abstract]
ABSTRACT: The present article focuses on the amphiphilic cationic polymers as antibacterial agents. These polymers undergo self-assembly in aqueous condition and impart biological activity by efficiently interacting with the bacterial cell wall, hence, used in preparing chemical disinfectants and biocides. Both cationic charge as well as hydrophobic segments facilitate interactions with the bacterial cell surface and initiate its disruption. The perturbation in transmembrane potential causes leakage of cytosolic contents followed by cell death. Out of two categories of macromolecules, peptide oligomers and cationic polymers, which have extensively been used as antibacterials, we have elaborated on the current advances made in the area of cationic polymer-based (naturally occurring and commonly employed synthetic polymers and their modified analogs) antibacterial agents. The development of polymer-based antibacterials has helped in addressing challenges posed by the drug-resistant bacterial infections. These polymers provide a new platform to combat such infections in the most efficient manner. This review presents concise discussion on the amphiphilic cationic polymers and their modified analogs having low hemolytic activity and excellent antibacterial activity against array of fungi, bacteria and other microorganisms.Current topics in medicinal chemistry 03/2015; 15(13). · 3.45 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Novel light-responsive nanoparticles based on an amphiphile with a single photolabile linker between its hydrophilic head and hydrophobic tail was developed for small interfering RNA (siRNA) delivery. Upon UV exposure, cleavage of the linkage resulted in rapid shell detachment of the nanoparticles, which facilitated siRNA release and enhanced gene silencing efficiency.RSC Advances 01/2014; 4(4):1961. DOI:10.1039/c3ra44866e · 3.71 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Here we report on a simple and flexible approach for continuous in situ fabrication of chitosan microfibers with controllable internals from tubular to peapod-like structures in microfluidics. Tubular and peapod-like jet templates can be generated at stable operation regions for template synthesis of chitosan microfibers with controllable tubular and peapod-like internals. The structure of each jet template can be precisely adjusted by simply changing the flow rates to tailor the structures of the resultant tubular and peapod-like chitosan microfibers. Both the tubular and peapod-like microfibers possess sufficient mechanical properties for further handling for biomedical applications. The tubular microfibers are used as biocompatible artificial vessels for transporting fluid, which is promising for delivering nutrition and blood for tissue engineering and cell culture. The peapod-like microfibers with controllable and separate oil cores can serve as multi-compartment systems for synergistic encapsulation of multiple drugs, showing great potential for developing drug-loaded medical patches for wound healing. The approach proposed in this study provides a facile and efficient strategy for controllable fabrication of microfibers with complex and well-tailored internals for biomedical applications.RSC Advances 01/2015; 5(2):928-936. DOI:10.1039/C4RA10696B · 3.71 Impact Factor