Pingtian Ding

Microdialysis sampling coupled to HPLC for transdermal delivery study of ondansetron hydrochloride in rats

The transdermal delivery of ondansetron hydrochloride (ON) solution in propylene glycol (PG) with a widely used penetration enhancer, oleic acid (OA), was studied in rats by a microdialysis sampling technique. Dialysate samples collected from the probe were directly injected into the HPLC system without any pre-treatment and no interference occurred in the blank sample. A good linearity between the standard concentrations and peak areas within the calibration range was achieved. In vivo recovery (32.52 +/- 1.8%) of the probe was assessed with the retrodialysis method, which was used to calculate the ON concentration in the dermis. Oleic acid at the concentrations of 2% and 5% (w/v) increased the steady-state delivery rate from 0.001 to 0.030 and 0.058 microg/h, respectively. OA proved to be an effective enhancer for transdermal delivery of ON in rats.

Preparation and Some Physicochemical Properties of Cross-Linked Poloxamer Hydrogel Spheres

The principal purpose of this paper is to report the preparation of cross-linked poloxamer hydrogel spheres in an aqueous two-phase system without the use of organic solvent and additional emulsifier and physicochemical properties related to drug release. Poloxamer 188 was modified with methacryloyl chloride to obtain the polymerizable derivative (macromer). The aqueous solution of the macromer was mixed with dextran/magnesium sulfate aqueous solution to form a water-in-water emulsion system. After polymerizing the macromer in the dispersion phase, nonporous particles with a mean diameter of micron level were prepared. Both the mean diameter and swelling ratio of spheres can be tailored by varying the starting composition of the preparations. The drug release experiments indicate that the release of vitamin B12 entrapped in the spheres follows first-order kinetics.

Disulfide-bond-containing agamatine-cystaminebisacrylamide polymer demonstrates better transfection efficiency and lower cytotoxicity than polyethylenimine in NIH/3T3 cells

Previously, we synthesized a non‐viral vector containing disulfide bond by polymerization of agamatine (AGM) and N,N′‐cystaminebisacrylamide (CBA). In this study, we investigated the transfection efficiency of disulfide bond (SS) containing AGM‐CBA polymer in gene delivery into NIH/3T3 cells, and examined the factors affecting its transfection efficiency by comparing with polyethylenimine (PEI). In addition, experiments were carried out to determine the mechanisms of cell entry pathways and intracellular behavior of AGM‐CBA/pDNA polyplexes. The transfection efficiency of AGM‐CBA/pDNA with different weight ratios and different amounts of pDNA was measured and the pathways mediated transfection processes were studied by using various endocytosis inhibitors. To determine the intracellular behavior of AGM‐CBA/pDNA polyplexes, the transfection efficiencies of AGM‐CBA/pDNA and PEI/pDNA polyplexes with different combination structures were determined by using reporter gene and fake plasmid DNA. The transfection efficiency of AGM‐CBA/pDNA polyplexes was correlated with its weight ratio of AGM‐CBA and pDNA, and the amount of pDNA. Both AGM‐CBA/pDNA and PEI/pDNA polyplexes enter into cell by clathrin‐ and caveolae‐mediated endocytic pathways. However, AGM‐CBA/pDNA showed different intracellular behavior in NIH/3T3 cells compared to PEI/pDNA polyplexes. It was hypothesized that disulfide bond in AGM‐CBA could be an important factor contributing to its intracellular behavior and better transfection efficiency. Overall, AGM‐CBA demonstrated better transfection efficiency and lower cytotoxicity than PEI in NIH/3T3 cells as a gene delivery vector.

Comparison of exosome-mimicking liposomes with conventional liposomes for intracellular delivery of siRNA

Graphical abstract Figure. No Caption available. Abstract Exosomes have been extensively explored as delivery vehicles due to low immunogenicity, efficient cargo delivery, and possibly intrinsic homing capacity. However, therapeutic application of exosomes is hampered by structural complexity and lack of efficient techniques for isolation and drug loading. Liposomes represent one of the most successful therapeutic nanocarriers, but are frequently criticized by short blood circulation and inefficient intracellular drug delivery. In this circumstance, a promising strategy is to facilitate a positive feedback between two fields. Herein, exosome‐mimicking liposomes were formulated with DOPC/SM/Chol/DOPS/DOPE (21/17.5/30/14/17.5, mol/mol), and harnessed for delivery of VEGF siRNA to A549 and HUVEC cells. Compared with Lipo 2000 and DOTAP liposomes, exosome‐mimicking liposomes exhibited less than four‐fold cytotoxicity but higher storage stability and anti‐serum aggregation effect. Exosome‐mimicking liposomes appeared to enter A549 cells through membrane fusion, caveolae‐mediated endocytosis, and macropinocytosis, while enter HUVEC through caveolae‐mediated endocytosis, which revealed that the uptake pathway was dependent on cell types. Notably, exosome‐mimicking liposomes exhibited significantly higher cellular uptake and silencing efficiency than PC‐Chol liposomes (>three‐fold), suggesting the unique lipid composition did enhance the intracellular delivery efficiency of exosome‐mimicking liposomes to a significantly greater extent. However, it still remained far from satisfactory delivery as compared to cationic Lipo 2000 and DOTAP liposomes, which warranted further improvement in future research. This study may encourage further pursuit of more exosome‐mimicking delivery vehicles with higher efficiency and biocompatibility.

Functionalized extracellular vesicles as advanced therapeutic nanodelivery systems

&NA; Extracellular vesicles (EVs) are membrane enclosed vesicles that are shed by almost all cell types, and play a fundamental role in cell‐to‐cell communication. The discovery that EVs are capable of functionally transporting nucleic acid‐ and protein‐based cargoes between cells, rapidly promotes the idea of employing them as drug delivery systems. These endogenous vesicles indeed hold tremendous promise for therapeutic delivery. However, issues associated with exogenously administered EVs, including rapid clearance by the immune system, apparent lack of targeting cell specificity, and insufficient cytoplasmic delivery efficiency, may limit their therapeutic applicability. In this review, we discuss recent research avenues in EV‐based therapeutic nanodelivery systems. Furthermore, we narrow our focus on the development of modification strategies to enhance the delivery properties of EVs, and elaborate on how to rationally harness these functionalized vesicles for therapeutic delivery. Graphical abstract Figure. No caption available.

Exosome-based small RNA delivery: Progress and prospects

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