Well-Defined Cationic N-[3-(Dimethylamino)propyl]methacrylamide Hydrochloride-Based (Co)polymers for siRNA Delivery.

Cationic glycopolymers have shown to be excellent candidates for the fabrication of gene delivery devices due to their ability to electrostatically interact with negatively charged nucleic acids and the carbohydrate residues ensure enhanced stability and low toxicity of the polyplexes. The ability to engineer the polymers for optimized compositions, molecular weights, and architectures is critical in the design of effective gene delivery vehicles. Therefore, in this study, the aqueous reversible addition-fragmentation chain transfer polymerization (RAFT) was used to synthesize well-defined cationic glycopolymers with various cationic segments. For the preparation of cationic parts, N-[3-(dimethylamino)propyl]methacrylamide hydrochloride (DMAPMA·HCl), water-soluble methacrylamide monomer containing tertiary amine, was polymerized to produce DMAPMA·HCl homopolymer, which was then used as macroCTA in the block copolymerization with two other methacrylamide monomers containing different pendant groups, namely, 2-aminoethyl methacrylamide hydrochloride (AEMA) (with primary amine) and N-(3-aminopropyl) morpholine methacrylamide (MPMA) (with morpholine ring). In addition, statistical copolymers of DMAPMA.HCl with either AEMA or MPMA were also synthesized. All resulting cationic polymers were utilized as macroCTA for the RAFT copolymerization with 2-lactobionamidoethyl methacrylamide (LAEMA), which consists of the pendent galactose residues to achieve DMAPMA·HCl-based glycopolymers. From the in vitro cytotoxicity study, the cationic glycopolymers showed better cell viabilities than the corresponding cationic homopolymers. Furthermore, complexation of the cationic polymers with siRNA, cellular uptake of the resulting polyplexes, and gene knockdown efficiencies were evaluated. All cationic polymers/glycopolymers demonstrated good complexation ability with siRNA at low weight ratios. Among these cationic polymer-siRNA polyplexes, the polyplexes prepared from the two glycopolymers, P(DMAPMA65-b-LAEMA15) and P[(DMAPMA65-b-MPMA63)-b-LAEMA16], showed outstanding results in the cellular uptake, high EGFR knockdown, and low post-transfection toxicity, suggesting the great potential in siRNA delivery of these novel glycopolymers.

Thermo-Responsive Poly(N-Isopropylacrylamide)-Cellulose Nanocrystals Hybrid Hydrogels for Wound Dressing.

Thermo-responsive hydrogels containing poly(N-isopropylacrylamide) (PNIPAAm), reinforced both with covalent and non-covalent interactions with cellulose nanocrystals (CNC), were synthesized via free-radical polymerization in the absence of any additional cross-linkers. The properties of PNIPAAm-CNC hybrid hydrogels were dependent on the amounts of incorporated CNC. The thermal stability of the hydrogels decreased with increasing CNC content. The rheological measurement indicated that the elastic and viscous moduli of hydrogels increased with the higher amounts of CNC addition, representing stronger mechanical properties of the hydrogels. Moreover, the hydrogel injection also supported the hypothesis that CNC reinforced the hydrogels; the increased CNC content exhibited higher structural integrity upon injection. The PNIPAAm-CNC hybrid hydrogels exhibited clear thermo-responsive behavior; the volume phase transition temperature (VPTT) was in the range of 36 to 39 °C, which is close to normal human body temperature. For wound dressing purposes, metronidazole, an antibiotic and antiprotozoal often used for skin infections, was used as a target drug to study drug-loading and the release properties of the hydrogels. The hydrogels showed a good drug-loading capacity at room temperature and a burst drug release, which was followed by slow and sustained release at 37 °C. These results suggested that newly developed drugs containing injectable hydrogels are promising materials for wound dressing.

Physicochemical properties and skin permeation of Span 60/Tween 60 niosomes of ellagic acid.

Ellagic acid (EA) is a potent antioxidant phytochemical substance which has limitation to use due to its poor biopharmaceutical properties, low solubility and low permeability. The aim of the present study was to develop niosomal formulations obtained from the mixture of Span 60 and Tween 60 that could encapsulate EA for dermal delivery. The EA-loaded niosomes were prepared with 1:0, 2:1, 1:1, 0:1 Span 60 and Tween 60, using polyethylene glycol 400 (PEG 400), propylene glycol (PG) or methanol (MeOH) as a solubilizer. The influence of formulations on vesicle size, entrapment efficiency and stability of EA-loaded niosomes was investigated. It was found that all ratios of surfactants could produce EA-loaded niosomes when using 15% (v/v) PG, 15% (v/v) PEG 400 or 20% (v/v) MeOH. The niosomes were spherical multilamellar vesicles showing the localization of EA in the vesicles. The vesicle sizes of the niosomes after extrusion were 124-752 nm with PI less than 0.4. The percentages of entrapment efficiency (% E.E.) of all EA-loaded niosomes varied between 1.35% and 26.75% while PEG 400 niosomes gave the highest % E.E. The most stable and highest entrapped formulation was 2:1 Span 60 and Tween 60 niosomes. Additionally, the in vitro skin permeation revealed that penetration of EA from the niosomes depended on vesicle size, the amount of EA entrapped and the added solubilizers which could act as a permeation enhancer. From skin distribution study, the EA-loaded niosomes showed more efficiency in the delivery of EA through human epidermis and dermis than EA solution. The results indicated that the Span 60 and Tween 60 niosomes may be a potential carrier for dermal delivery of EA.