Geun-woo Jin

Biodegradable branched poly(ethylenimine sulfide) for gene delivery

We synthesized biodegradable b-PEIS (branched poly(ethylenimine sulfide)) by crosslinking linear PEIS. We controlled the degree of crosslinking and molecular weight by adjusting the amount of the crosslinker, bisepoxide. The b-PEIS was readily degradable under reductive conditions (5mm glutathione solution) and the degradation time was dependent on the degree of crosslinking. We controlled the molecular weights of the b-PEIS by regulating the amount of crosslinker and thus, the degree of crosslinking. Our titration data showed that there was almost no loss in buffering ability before or after bisepoxide crosslinking. We verified the degradation of this polymer by MALLS and gel electrophoresis, and confirmed that there was a high transfection efficiency and low cytotoxicity based on cellular data. Intracellular trafficking was observed by image restoration microscopy, demonstrating that b-PEIS does not accumulate in the cell interior.

A new biodegradable crosslinked polyethylene oxide sulfide (PEOS) hydrogel for controlled drug release

We developed a polyethylene glycol (PEG)-based biodegradable hydrogel through disulfide crosslinking of polyethylene oxide sulfide (PEOS). The crosslinking rate was highly dependent on temperature, and incubation at about 40-50 degrees C was required for efficient crosslinking. The crosslinked PEOS hydrogel showed glutathione-dependent dissolution and corresponding controlled release of a model drug-fluorescein isothiocyanate (FITC)-labeled dextran-because the disulfide bond, the main linker, is selectively degraded in response to the high concentration of glutathione. The temperature-sensitive crosslinking and the hydrogel formation have the potential for use as an injectable biogel precursor, which was confirmed by in situ gel formation in mice.

Ion pairs of risedronate for transdermal delivery and enhanced permeation rate on hairless mouse skin

Ion-paired solutions of risedronate (RIS) with L-arginine (ARG), L-lysine (LYS), and diethylenetriamine (DETA) were tested in vitro for their potential to enhance the penetration of RIS across the skin of hairless mouse. The xylene solubilities of RIS paired with ARG, LYS, and DETA in molar ratios of 1:2, 1:2, and 1:1 were 8.9%, 12.0%, and 2.1%, respectively, in comparison with the solubility in deionized water, but non-ion-paired RIS was not detected in xylene. In vitro permeation tests were performed on the skin of hairless mice, and the results indicated that ion-paired RIS could penetrate mice skin about 36 times more effectively than RIS alone. The cumulative amount of ion paired RIS after 24 h resulted in 475.18±94.19 μg/cm(2) and 511.21±106.52 μg/cm(2) at molar ratio of 1:2 and 1:1. The cumulative amount of RIS alone was as low as 14.13±5.49 μg/cm(2) in 24h. The hairless mice showed no skin irritation after a single administration of RIS alone and ion-paired RIS (1:2 molar ratio with ARG, and 1:1 molar ratio with DETA). In this study, we found that RIS can be delivered transdermally, and the ion-paired system in an aqueous solution showed an enhanced flux through the skin barrier.

Effect of deoxycholate conjugation on stability of pDNA/polyamidoamine-diethylentriamine (PAM-DET) polyplex against ionic strength

Polyplexes formed from cationic polymer/pDNA have been known to be vulnerable to external ionic strength. To improve polyplex stability against ionic strength, we attempted the chemical conjugation of the hydrophobic deoxycholate (DC) moiety to the polyamidoamine-diethylenetriamine (PAM-DET) dendrimer. Dynamic light scattering studies showed that the tolerance of the resulting PAM-DET-DC against ionic strength is higher than that of PAM-DET. In addition, we confirmed that the stability of polyplex has a strong relationship with the degree of conjugation of the DC moiety to the PAM-DET dendrimer and the charge ratio of PAM-DET-DC. Furthermore, the transfection efficiency of the PAM-DET-DC polyplex is higher than that of PAM-DET but its cytotoxicity remains the same. Therefore, the chemical conjugation of DC is a safe and effective method for increasing the stability of supramolecules formed from electrostatic interaction.

Formation of polyion complex micelles with tunable isoelectric points based on zwitterionic block copolymers

AbstractZwitterionic block copolymers can form polyion complex (PIC) micelles without any additional ionic compounds because their backbones contain both cationic and anionic residues. For the generation of polyion complex (PIC) micelles with tunable isoelectric points (pI), the zwitterionic block copolymers, poly(ethylene oxide)45-b-[poly(2-succinyloxyethyl methacrylate)x-r-poly(2-(dimethylamino)ethyl methacrylate)y] (PEO45-b-(PSEMAx-r-PDMAy)) zwitterionic block copolymers were synthesized via atom transfer radical polymerization (ATRP) of 2-hydroxyethyl methacrylate (HEMA) and 2-(dimethylamino)ethyl methacrylate (DMA), and subsequent succinylation of the hydroxy groups on HEMA. The electrostatic interaction between oppositely charged 2-succinyloxyethyl methacrylate (SEMA) and DMA residues led to spontaneous micelle formation of the zwitterionic block copolymers in an aqueous solution. The pH-dependent protonation/deprotonation behavior of the SEMA and DMA residues induced a change in the net charge of the micelle. Since the pIs of PIC micelles are closely related to the SEMA to DMA ratio (x/y) of the zwitterionic block, PIC micelles with certain pI values, which can be predicted by simple calculations based on the average pKa values of DMA and SEMA, can be easily tailored to achieve our objectives.