Dataset Information

PH-Triggered Sheddable Shielding System for Polycationic Gene Carriers.

ABSTRACT: For improving the therapeutic efficiency of tumors and decreasing undesirable side effects, ternary complexes were developed by coating pH-sensitive PEG-b-PLL-g-succinylsulfathiazole (hereafter abbreviated as PPSD) with DNA/PEI polyplexes via electrostatic interaction. PPSD can efficiently shield the surface charge of DNA/PEI. The gene transfection efficiency of ternary complexes was lower than that of DNA/PEI at pH 7.4; however, it recovered to the same level as that of DNA/PEI at pH 6.0, attributed to the pH-triggered release of DNA/PEI from ternary complexes. Cell uptake results also exhibited the same trend as transfection at different pH values. The suitable ability for pH-triggered shielding/deshielding estimated that PPSD demonstrates potential as a shielding system for use in in vivo gene delivery.

SUBMITTER: Xia J

PROVIDER: S-EPMC6432142 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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pH-Triggered Sheddable Shielding System for Polycationic Gene Carriers.

Xia Jialiang J Tian Huayu H Chen Jie J Lin Lin L Guo Zhaopei Z Han Bing B Yang Hongyan H Feng Zongcai Z

Polymers 20160414 4

For improving the therapeutic efficiency of tumors and decreasing undesirable side effects, ternary complexes were developed by coating pH-sensitive PEG-<i>b</i>-PLL-<i>g</i>-succinylsulfathiazole (hereafter abbreviated as PPSD) with DNA/PEI polyplexes via electrostatic interaction. PPSD can efficiently shield the surface charge of DNA/PEI. The gene transfection efficiency of ternary complexes was lower than that of DNA/PEI at pH 7.4; however, it recovered to the same level as that of DNA/PEI at ...[more]

PMID: 30979234

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Project description:Cationic nanocarriers offer a promising solution to challenges in delivering drugs to negatively charged connective tissues, such as to articular cartilage for the treatment of osteoarthritis (OA). However, little is known about the effects that cationic macromolecules may have on the mechanical properties of cartilage at high interstitial concentrations. We utilized arginine-rich cationic peptide carriers (CPCs) with varying net charge (from +8 to +20) to investigate the biophysical mechanisms of nanocarrier-induced alterations to cartilage biomechanical properties. We observed that CPCs increased the compressive modulus of healthy bovine cartilage explants by up to 70% and decreased the stiffness of glycosaminoglycan-depleted tissues (modeling OA) by 69%; in both cases, the magnitude of the change in stiffness correlated with the uptake of CPC charge variants. Next, we directly measured CPC-induced osmotic deswelling in cartilage tissue due to shielding of charge repulsions between anionic extracellular matrix constituents, with magnitudes of reductions between 36 and 64 kPa. We then demonstrated that electrostatic interactions were required for CPC-induced stiffening to occur, evidenced by no observed increase in tissue stiffness when measured in hypertonic bathing salinity. We applied a non-ideal Donnan osmotic model (under triphasic theory) to separate bulk modulus measurements into Donnan and non-Donnan components, which further demonstrated the conflicting charge-shielding and matrix-stiffening effects of CPCs. These results show that cationic drug carriers can alter tissue mechanical properties via multiple mechanisms, including the expected charge shielding as well as a novel stiffening phenomenon mediated by physical linkages. We introduce a model for how the magnitudes of these mechanical changes depend on tunable physical properties of the drug carrier, including net charge, size, and spatial charge distribution. We envision that the results and theory presented herein will inform the design of future cationic drug-delivery systems intended to treat diseases in a wide range of connective tissues.

Dataset Information

PH-Triggered Sheddable Shielding System for Polycationic Gene Carriers.

Publications

pH-Triggered Sheddable Shielding System for Polycationic Gene Carriers.

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