-
Wei Fan,
Xin Wu, Baoyue Ding,
Jing Gao,
Zhen Cai,
Wei Zhang,
Dongfeng Yin,
Xiang Wang,
Quangang Zhu,
Jiyong Liu,
Xueying Ding,
Shen Gao
[show abstract]
[hide abstract]
ABSTRACT: Cationic copolymers consisting of polycations linked to nonionic amphiphilic block polymers have been evaluated as nonviral gene delivery systems, and a large number of different polymers and copolymers of linear, branched, and dendrimeric architectures have been tested in terms of their suitability and efficacy for in vitro and in vivo transfection. However, the discovery of new potent materials still largely relies on empiric approaches rather than a rational design. The authors investigated the relationship between the polymers' structures and their biological performance, including DNA compaction, toxicity, transfection efficiency, and the effect of cellular uptake.
This article reports the synthesis and characterization of a series of cationic copolymers obtained by grafting polyethyleneimine with nonionic amphiphilic surfactant polyether-Pluronic(®) consisting of hydrophilic ethylene oxide and hydrophobic propylene oxide blocks. Transgene expression, cytotoxicity, localization of plasmids, and cellular uptake of these copolymers were evaluated following in vitro transfection of HeLa cell lines with various individual components of the copolymers.
Pluronics can exhibit biological activity including effects on enhancing DNA cellular uptake, nuclear translocation, and gene expression. The Pluronics with a higher hydrophilic-lipophilic balance value lead to homogeneous distribution in the cytoplasm; those with a lower hydrophilic-lipophilic balance value prefer to localize in the nucleus.
This Pluronic-polyethyleneimine system may be worth exploring as components in the cationic copolymers as the DNA or small interfering RNA/microRNA delivery system in the near future.
International Journal of Nanomedicine 01/2012; 7:1127-38. · 3.13 Impact Factor
-
Wei Zhang, Baoyue Ding,
Renjie Tang,
Xueying Ding,
Xuemei Hou,
Xiaoyu Wang,
Shengying Gu,
Lei Lu,
Yi Zhang,
Shen Gao,
Jing Gao
[show abstract]
[hide abstract]
ABSTRACT: Penetration of PLGA nanoparticles in the hairless mouse skin petreated by microneedles was studied in vitro using nanoparticles containing coumarin 6 and R-phycoerythrin (R-PE) as fluorescent probe. Confocal laser scanning microscopy (CLSM) was used to visualize the distribution of nanoparticles and the high performance liquid chromatography (HPLC) was utilized to quantify the amount of the nanoparticles. The CLSM images revealed that nanoparticles (diameter 160.1± 1.97nm) could penetrate into the skin through the microconduits created with microneedles and reach the depth of more than 42.19µ m. The quantitative results showed that the amount of nanoparticles deposited in the skin increased by microneedles was about twice that in the control group in a period of 48h. However, the nanoparticle was not able to reach the receptor compartment. In additional, the penetration and the distribution of nanoparticles was significantly influenced by the particle size (diameter ranged from 160.1± 1.97nm to 288.2± 6.62nm). These results suggested that the combination of PLGA nanoparticles with microneedles could be a useful method to increase topical drug delivery and improving therapy by supplying drug reservoirs to the skin.
Current Nanoscience 07/2011; 7(4):545-551. · 1.78 Impact Factor
-
Xin Wu, Baoyue Ding,
Jing Gao,
Huanyun Wang,
Wei Fan,
Xiang Wang,
Wei Zhang,
Xiaoyu Wang,
Lihua Ye,
Min Zhang,
Xueying Ding,
Jiyong Liu,
Quangang Zhu,
Shen Gao
[show abstract]
[hide abstract]
ABSTRACT: miR-15a and miR-16-1 have been identified as tumor suppressor genes in prostate cancer, but their safe and effective delivery to target cells is key to the successful use of this therapeutic strategy. RNA aptamer A10 has been used as a ligand, targeting prostate cancer cells that express prostate-specific membrane antigen (PSMA). Compared with A10, the binding of the second-generation RNA aptamer, A10-3.2, to PSMA is more efficient.
A10-3.2 was investigated as a PSMA-targeting ligand in the design of a polyamidoamine (PAMAM)-based microRNA (miR-15a and miR-16-1) vector to prostate cancer cells. Using polyethyleneglycol (PEG) as a spacer, PAMAM was conjugated to aptamer (PAMAM-PEG-APT) and used as a vehicle for miRNA target delivery.
Luciferase assays of pGL-3 expression against PC3 (PSMA(-)) and LNCaP (PSMA(+)) cells demonstrated that the transfection efficiency of the synthesized DNA/PAMAM-PEG-APT complex was higher than that of the DNA/PAMAM-PEG complex. In addition, cell viability assays of LNCaP (PSMA(+)) cells showed that, with a N/P ratio of 15:1, the IC(50) value of miRNA/PAMAM-PEG-APT was approximately 4.7-fold lower than that of miRNA/PAMAM-PEG.
This PSMA-targeted system may prove useful in widening the therapeutic window and allow for selective killing of prostate cancer cells.
International Journal of Nanomedicine 01/2011; 6:1747-56. · 3.13 Impact Factor
-
Baoyue Ding,
Xin Wu,
Wei Fan,
Zhaoyong Wu,
Jing Gao,
Wei Zhang,
Lulu Ma,
Wang Xiang,
Quangang Zhu,
Jiyong Liu,
Xueying Ding,
Shen Gao
[show abstract]
[hide abstract]
ABSTRACT: The increased incidence of malignant melanoma in recent decades, along with its high mortality rate and pronounced resistance to therapy pose an enormous challenge. Novel therapeutic strategies, such as immunotherapy and targeted therapy, are urgently needed for melanoma. In this study, a new active targeting drug delivery system was constructed to combine chemotherapy and active specific immunotherapy.
The chemotherapeutic drug, dacarbazine (DTIC), that induces apoptosis through the intrinsic pathway which typically responds to severe DNA damage, was used as a model drug to prepare DTIC-loaded polylactic acid (PLA) nanoparticles (DTIC-NPs), which were covalently conjugated to a highly specific targeting functional TRAIL-receptor 2 (DR5) monoclonal antibody (mAb) that can contribute directly to cancer cell apoptosis or growth inhibition through the extrinsic pathway.
Our in vitro experiments demonstrated that DTIC-PLA-DR5 mAb nanoparticles (DTIC-NPs-DR5 mAb) are an active targeting drug delivery system which can specifically target DR5-overexpressing malignant melanoma cells and become efficiently internalized. Most strikingly, compared with conventional DTIC-NPs, DTIC-NPs-DR5 mAb showed significantly enhanced cytotoxicity and increased cell apoptosis in DR5-positive malignant melanoma cells.
The DTIC-NPs-DR5 mAb described in this paper might be a potential formulation for targeting chemotherapy and immunotherapy to DR5-overexpressing metastatic melanoma.
International Journal of Nanomedicine 01/2011; 6:1991-2005. · 3.13 Impact Factor
-
Wei Zhang,
Jing Gao,
Quangang Zhu,
Min Zhang,
Xueying Ding,
Xiaoyu Wang,
Xuemei Hou,
Wei Fan, Baoyue Ding,
Xin Wu,
Xiying Wang,
Shen Gao
[show abstract]
[hide abstract]
ABSTRACT: This study was designed to investigate the penetration and the distribution of poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles in the human skin treated with microneedles. Fluorescent nanoparticles were prepared to indicate the transdermal transport process of the nanoparticles. Permeation study was performed on Franz-type diffusion cells in vitro. The distribution of nanoparticles was visualized by confocal laser scanning microscopy (CLSM) and quantified by high performance liquid chromatography (HPLC). CLSM images showed that nanoparticles were delivered into the microconduits created by microneedles and permeated into the epidermis and the dermis. The quantitative determination showed that (i) the permeation of nanoparticles into the skin was enhanced by microneedles, but no nanoparticle reached the receptor solution; (ii) much more nanoparticles deposited in the epidermis than those in the dermis; (iii) the permeation was in a particle size-dependent manner; and (iv) the permeation increased with the nanoparticle concentration increasing until a limit value was reached. These results suggested that microneedles could enhance the intradermal delivery of PLGA nanoparticles. The biodegradable nanoparticles would sustain drug release in the skin and supply the skin with drug over a prolonged period. This strategy would prove to be useful for topical drug administration.
International journal of pharmaceutics 10/2010; 402(1-2):205-12. · 2.96 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study was to investigate the suitability of poly-(d,l-lactic acid-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA triblock copolymer as a matrix material for a sustained-release system for docetaxel (DTX). The copolymers were synthesized by ring-opening polymerization reaction and characterized by (1)H-NMR and gel permeation chromatography. The DTX-loaded formulations were prepared, characterized. And the antitumor efficacy and the pharmacokinetics of DTX-loaded copolymer on A-549 lung tumor-bearing BALB/cA mice were investigated. The results showed that DTX-loaded copolymer highly increased the solubility of DTX by more than 3000-fold. And copolymer concentration as well as drug loading level exerted appreciable influence on the drug release behavior. Further, the pharmacokinetic test showed that DTX-loaded copolymer could be with the sustained-release nature for over 3 weeks, which correlated well with the in vitro release. Additionally, one intratumoral injection of the thermo-sensitive hydrogel containing DTX was comparable to three intravenous injections of DTX injection in inhibiting the tumor growth in A-549 lung tumor-bearing BALB/cA mice with a less toxic manner. PLGA-PEG-PLGA could thus provide a promising alternate locally delivered vehicle for DTX to achieve prolonged exposure having greater efficacy in inhibiting tumor growth with lower toxicity.
Journal of Drug Targeting 09/2010; 19(7):516-27. · 2.70 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purposes of this study were to improve the transdermal permeation of the Shangwu traumatic formula by chemical penetration enhancers and to investigate the pharmacodynamic changes of the formula caused by incorporated enhancers. The effects of different enhancers on the transdermal absorption of piperine, the representative component of formula, were investigated by in vitro permeation studies. The tests showed an increasing enhancement effect in the following order: Azone/N-methylpyrrolidone (NMP) > oleic acid > Azone/peppermint oil > Azone/oleic acid > Azone/propylene glycol > Azone > peppermint oil > NMP > propylene glycol. The ratio and the content of the most effective enhancer Azone/NMP were determined subsequently. The results suggested that the most significant penetration enhancement was achieved by 3% (w/w) Azone/NMP (3:7). Furthermore, the in vivo pharmacodynamic responses of the formula suspension with or without Azone/NMP were compared using hot-plate assay and xylene-induced ears edema test as models. The data indicated that the formula had positive effect on analgesis and anti-inflammatory, which can be enhanced with the addition of enhancers.
European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 09/2009; 73(3):385-90. · 3.15 Impact Factor
