DRUG DELIVERY
·
2019
·
IF 3.829
Yujia Zhang,Nan Zhang,Hui Song,He Li,Jin Wen,Xiaochuan Tan,Wensheng Zheng
Gout is a kind of joint disease characterized by the accumulation of monosodium urate (MSU) crystals in the joint and its surrounding tissue, causing persistent hyperuricemia. Colchicine is the first choice of treatment for acute gout attacks. Due to strong toxicity of colchicines oral tablets, there are high fluctuations of blood drug concentration and serious irritation of gastrointestinal tract, and hence a transdermal preparation can help to slow down the blood drug concentration, reduce the frequency of drug taking, and improve the patients' compliance of the drug. The ethosome is a lipid carrier with high concentration of ethanol and has been proved to promote the penetration of drugs into the skin. Borneol (BO) is an excellent penetration enhancer in Chinese medicine, which can promote the entry of drugs into the skin. This paper prepared the borneol-physically-modified colchicine ethosome (COL-bpES) and used the prepared borneol-dioleoyl phosphoethanloamine (BO-DOPE) to prepare borneol-chemically-modified colchicine ethosome (COL-bcES). Compared to the free colchicine aqueous solution (free COL) and normal colchicine ethosome (COL-ES), the borneol-modified colchicine ethosome (COL-bES) demonstrated better drug penetration effect, while the particle size of the COL-bcES was lower than that of the COL-bpES. Toxicity, in vitro diffusion, pharmacokinetics and pharmacodynamics are superior to those of COL-bpES, providing a better delivery system for the treatment of small molecule inflammatory drugs.
研究领域:
药剂学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2019
·
IF 4.959
Wanling Cai,Mengyu Guo,Xiulan Weng,Wei Zhang,Zuliang Chen
Since Fe 3 O 4 nanoparticles synthesized by plant extracts possess good bio-compatibility and superparamagnetic properties, the possibility of these could be used as a carrier in drug delivery. In this work, doxorubicin hydrochloride (DOX), an anti-cancer drug, loaded on glutaric anhydride-functionalized magnetic nanoparticles (Fe 3 O 4 @SiO 2 -Glu) was investigated at varying pH values for effective drug delivery. Various factors affecting the adsorption of DOX onto the Fe 3 O 4 @SiO 2 -Glu were examined, where the adsorption efficiency of DOX reached 92% at a concentration of 20 mg/L employing 10 mg of Fe 3 O 4 @SiO 2 -Glu at 303 K in pH 7.4. However, the adsorption efficiency of DOX was decreased to 18% at acidic pH value down to 3.0, implicating that the drug releasing process was controlled by pH. Adsorption kinetics was fitting to pseudo-second-order and the isothermal adsorption conformed to Freundlich isotherm. The morphology and surface composition of the synthesized Fe 3 O 4 @SiO 2 -Glu were characterized by SEM, TEM , and N 2 adsorption/desorption isotherms, revealing that the specific surface area being 62.6 m 2 /g and the size ranging from ~30 to 50 nm. The zeta potential results indicated that Fe 3 O 4 @SiO 2 -Glu were negatively charged in various pH from 3 to 8.5. Characterizations by FTIR and UV–Vis techniques suggested that the DOX was absorbed and it can be delivered by Fe 3 O 4 @SiO 2 -Glu.
研究领域:
生物医学工程
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2012
·
IF 3.35
Anning Wang,Hui Gao,Yanfang Sun,Yu-long Sun,Ying-Wei Yang,Guolin Wu,Yinong Wang,Yunge Fan,Jianbiao Ma
A series of temperature- and pH-responsive polyurethanes based on hexamethylene diisocyanate (HDI) and 4,4′-diphenylmethane diisocyanate (MDI) were synthesized by a coupling reaction with bis-1,4-(hydroxyethyl) piperazine (HEP), N -methyldiethanolamine (MDEA) and N -butyldiethanolamine (BDEA), respectively. The chemical structure , molecular weight, thermal property and crystallization properties were characterized by Fourier transform infrared (FT-IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, gel permeation chromatography (GPC), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) spectroscopy. The resulting polyurethanes were then used to prepare nanoparticles either by direct dispersion method or dialysis method. Their pH and temperature responsibilities were evaluated by optical transmittance and size measurement in aqueous media. Interestingly, HDI-based and MDI-based polyurethanes exhibited different pH and temperature responsive properties. Nanoparticles based on HDI-HEP and HDI-MDEA were temperature-responsive, while MDI-based biomaterials were not. All of them showed pH-sensitive behavior. The possible responsive mechanism was investigated by 1 H NMR spectroscopy. The cytotoxicity of the polyurethanes was evaluated using methylthiazoletetrazolium (MTT) assay in vitro . It was shown that the HDI-based polyurethanes were non-toxic, and could be applied to doxorubicin (DOX) encapsulation. The experimental results indicated that DOX could be efficiently encapsulated into polyurethane nanoparticles and uptaken by Huh-7 cells. The loaded DOX molecules could be released from the drug-loaded polyurethane nanoparticles upon pH and temperature changes, responsively.
研究领域:
生物材料学
·
药剂学
·
肿瘤学
·
高分子科学
·
纳米医学
✓ 已验证
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2019
·
IF 4.396
Yina Song,Yanan Shi,Liping Zhang,Haiyan Hu,Chunyan Zhang,Miaomiao Yin,Liuxiang Chu,Xiuju Yan,Mingyu Zhao,Xuemei Zhang,Hongjie Mu,Kaoxiang Sun
The oral absorption of exenatide, a drug for type 2 diabetes treatment, can be improved by using nanoparticles (NPs) for its delivery. To improve the mucus penetration and intestinal absorption of exenatide, we designed a block copolymer, CSKSSDYQC-dextran-poly(lactic-co-glycolic acid) (CSK-DEX-PLGA), and used it for the preparation of exenatide-loaded NPs. The functionalized exenatide-loaded NPs composed of CSK-DEX-PLGA were able to target intestinal epithelial cells and reduce the mucus-blocking effect of the intestine. Moreover, the CSK modification of DEX-PLGA was found to significantly promote the absorption efficiency of NPs in the small intestine based on in vitro ligation of the intestinal rings and an examination of different intestinal absorption sites. Compared to DEX-PLGA-NPs (DPs), the absorption of CSK-DEX-PLGA-NPs (CDPs) was increased in the villi, allowing the drug to act on gobletlike Caco-2 cells through clathrin-, caveolin-, and gap-mediated endocytosis. Furthermore, the enhanced transport ability of CDPs was observed in a study on Caco-2/HT-29-MTX cocultured cells. CDPs exhibited a prolonged hypoglycemic response with a relative bioavailability of 9.2% in diabetic rats after oral administration. In conclusion, CDPs can target small intestinal goblet cells and have a beneficial effect on the oral administration of macromolecular peptides as a nanometer-sized carrier.
研究领域:
药剂学
·
生物医学工程
·
糖尿病治疗
✓ 已验证
DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2019
·
IF 2.367
Jingwen Luo,Jiang Sun,Xiaoting Luo,Yinghui Wei,Hangsheng Zheng,Chaofeng Mu,Wenjie Yao
Objective: This article aims to design low molecular weight chitosan (LMWC)-based conjugates of Rhein (RH) by means of an amino acid linker (Alanine) for improved solubility and enhanced bioavailability.Significance: Rhein is a potential candidate for the therapy of kidney disease. However, the poor solubility, inadequate bioavailability, and lack of proper formulation restrict its clinical applicability. LMWC-drug conjugates offer the potential to improve the water-solubility of RH, increase its oral absorption, and thereby enhance its bioavailability.Methods: The conjugates were synthesized via a carbodiimide reaction and confirmed using UV-vis, FTIR, and 1H-NMR spectroscopy. The water-solubility and in vitro release properties were evaluated. Free RH and RH-LMWC conjugates were administered at an equivalent oral gavage dose of RH at 35 mg/kg for pharmacokinetic studies in Sprague Dawley rats.Results: The conjugates with RH content of 9.65% were successfully synthesized and featured a satisfactory water-solubility of 9.73 mg/mL, which exhibited a sustained release pattern over 72 h, and the enzymes present may promote the degradation of the conjugate to increase the release of Rhein. Oral administration of RH-LMWC conjugates to rats led to seven-folds and 3.1-folds increase in the T1/2 and AUC0–∞, respectively, as compared to RH suspension.Conclusion: The present work demonstrated that the RH-LMWC conjugates exhibited sustained release properties with outstanding oral bioavailability enhancements compared to administration of RH itself. Potentially, RH-LMWC conjugates may serve as a promising lead for developing a new platform for RH oral delivery.
研究领域:
药剂学
·
药物化学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2019
·
IF 3.829
Jin Li,Tongjie Cheng,Qiang Tian,Ying Cheng,Lixia Zhao,Xingzhen Zhang,Yi Qu
As a leading cause of vision impairment of the retina, macular edema (ME) has one of the highest clinical demands for treatment. Current treatment of ME relies heavily on invasive techniques resulting in complications and poor patient compliance. To enhance the efficiency of triamcinolone acetonide as eye drop to the posterior segment of the eye, we developed and characterized a novel formulation, namely, triamcinolone acetonide chitosan-coated liposomes (TA-CHL), prepared by the calcium acetate gradient method with some modifications. TA-CHL provided the mean particle size of 135.46 ± 4.49 nm and high entrapment efficiency (90.66 ± 3.21%), exhibited a sustained release profile, excellent physical stability, and no significant toxicity on cornea, conjunctiva, and retina. Optical coherence tomography system (OCT) was used to detect pharmacokinetics of CHL in vivo, indicating that CHL had good potency for drug delivery. Cellular uptake experiments showed CHL had the higher transduction efficiency into HCEC and ARPE-19 than liposomes. TA-CHL was shown to be potentially effective eye drop to contribute to the posterior segment of the eye.
研究领域:
药剂学
·
眼科医学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR MATERIALS AND ENGINEERING
·
2018
·Vol. 303
·期 9
·1800060
·
IF 2.69
Titao Jing,Tuanwei Li,Zheng Ruan,Quan Cheng,Lifeng Yan
A negatively charged polypeptide nanogel, near-infrared (NIR) cyanine dye (Cy5.5) conjugated and 2,3-dimethylmaleic anhydride (DMA) modified poly- l -lysine-co- l -cystine (CDPLC), is synthesized and is used as an imaging-guided sequential drug delivery system. The CDPLC nanogel can respond to two general stimulations in sequence: extracellular tumor acidic microenvironment pHe (6.8–6.5) and intracellular high concentration glutathione (GSH). Under pHe, the DMA shell of the nanogel is removed and a charge reversal takes place, resulting in positively charged nanogel which can be internalized by cancer cells easily. Once internalized into tumor cells, the increased intracellular GSH concentration further promotes DOX release from the nanogel and DOX is enriched to the nucleus. Cy5.5 is conjugated to the nanogel as an NIR fluorescent probe, making it possible for imaging-guided drug delivery, which is confirmed by the MTT and confocal laser scanning microscopy via in vitro experiments. The as-prepared nanogel is a potential theranostic for cancer therapy.
研究领域:
肿瘤学
·
药剂学
·
分子影像学
·
生物材料
·
纳米医学
·
药物递送系统
✓ 已验证
DOI
高影响因子
MATERIALS LETTERS
·
2013
·
IF 2.224
Kejie Yu,Xuebin Zhang,Hongwu Tong,Xiangyan Yan,Shaomin Liu
Fibrous monodisperse core–shell structured Fe 3 O 4 /SiO 2 /KCC-1 nanoparticles were synthesised successfully through a surfactant-templated microemulsion formation process. The structure and morphology of the synthesised nanoparticles were investigated by scanning electron microscopy , transmission electron microscopy , superconducting quantum interference device susceptometer, X-ray diffraction, thermogravimetric analysis and N 2 adsorption/desorption. These nanoparticles showed monodisperse spherical morphology, high magnetism , good thermal stability , large surface area , direct channels, easily accessible large pores and narrow size distribution. A mechanism for the synthesis of these nanoparticles was proposed and explained. Adsorption experiments indicated that the as-prepared materials had good adsorption capacity for dye and could perform a fast transfer of molecules, indicating its promising application in purification of industrial wastewater, drug delivery and so on.
研究领域:
纳米医学
·
材料科学
·
环境工程
·
生物材料
·
药剂学
·
胶体与界面化学
✓ 已验证
DOI
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 80
·76905-76914
·
IF 3.289
Liujie Zhang,Ying Kuang,Jia Liu,Zhilan Liu,Shiwen Huang,Renxi Zhuo
In this paper, a receptor-mediated liposomal drug delivery system (DDS) was developed aiming to deliver cisplatin (cis-diaminedichloroplatinum(II); CDDP) targeting the liver. Acetyl glycyrrhetinic acid (AGA) was chosen as the hepatic targeting ligand and acetyl glycyrrhetinic acid-poly(ethylene glycol)-stearate (AGA-PEG-ST) was synthesized. Anionic 5-cholestene-3-beta-ol-3-hemisuccinate (CHO-HS) was also synthesized. The liposomal CDDPs were prepared by employing these functional moieties with phosphatidylcholine (PC) at various ratios. Meanwhile, methoxypolyethylene glycol-stearate (MPEG-ST) with an analogous structure but without AGA was also prepared as a control. The particle sizes of AGA modified liposomes ranged from 120 nm to 180 nm and the zeta potentials were located between −39.7 mV and −3.18 mV. The liposomes had encapsulation percentages of 51.5–61.7% and a loading capacity of 23.2–26.7% for CDDP. The transmission electron microscopy (TEM) observations showed that the liposomes had spherical morphologies with homogeneous distribution. In vitro cytotoxicity of CDDP-loaded liposomes against HepG2 human liver cancer cells and A549 human lung epithelial carcinoma cells were evaluated by MTT assays. The results demonstrated that the introduction of AGA could enhance the cytotoxicity of liposomal CDDP against HepG2 cells but showed less significant impact on A549 cells. CLSM observation and FCM measurement further confirmed that AGA modified liposomes had a stronger affinity to HepG2 cells than that of liposomes without AGA. The tissue distribution of calcein in mice indicated that AGA modified liposomes resulted in higher accumulation in the liver than that of liposomes without the AGA ligand. These results demonstrated the promise of AGA decorated anionic liposomes for hepatic targeted delivery of cisplatin.
研究领域:
药剂学
·
肿瘤学
·
纳米医学
·
药物递送系统
·
肝病学
✓ 已验证
DOI
高影响因子
RSC Advances
·
2014
·Vol. 4
·期 39
·20208-20215
·
IF 3.708
Lei Sun,Xinge Zhang,Jinxia An,Cui Su,Qianqain Guo,Chaoxing Li
Currently, the major challenge for cancer treatment is to develop simple and smart nanocarriers that can efficiently retain the encapsulated drug during blood circulation, recognize tumor cells and quickly release the drug under stimulation. In this paper, such a pH-sensitive core–shell composite nanoparticles is prepared based on a 3-aminophenylboronic acid modified mesoporous silica nanoparticles (MSN–APBA) core coated with a lactobionic acid grafted chitosan (CS–LA) shell via boronate ester bonds. The MSN core increases drug loading capacity and stability, and lactobionic acid offers abundant diols which can form pH sensitive boronate ester bonds with APBA on MSN. Meanwhile, the lactobionic acid-conjugated shell could also efficiently target the asialoglycoprotein receptor over expressing hepatoma cells. The successful synthesis of CS–LA and MSN–APBA is confirmed by the results of TGA, TEM, DLS, FT-IR, 1H-NMR and N2 adsorption–desorption. Doxorubicin hydrochloride (DOX) is applied as a model drug and the behaviors of drug loading/release are investigated. The drug loading behavior is pH-dependent, and its drug encapsulation efficiency is near 80% and loading capacity is 13.05%. The results of cumulative in vitro release indicate that at neutral pH, the pores of the MSN are effectively capped with a polymer shell and the drug release is strongly inhibited, almost zero release. While at acidic pH, the hydrolysis of the boroester bond takes place and thus results in a rapid release of the entrapped drug. The cytotoxicity assay indicates high cell biocompatibility of this material and it is suitable as a drug carrier. When loaded with DOX, it presents distinctly cytotoxic behavior to HepG2 cells, due to the sustained release of drug. These results imply that the core–shell nanoparticles are promising platforms to construct simple and effective pH-responsive controlled drug delivery systems for cancer therapy.
研究领域:
肿瘤学
·
药剂学
·
纳米医学
·
生物材料
·
分子药理学
·
靶向治疗
✓ 已验证
DOI
高影响因子
MACROMOLECULAR CHEMISTRY AND PHYSICS
·
2012
·Vol. 213
·期 20
·2192-2200
·
IF 2.361
Xiao-Hui Dai,Chun-Yan Hong,Cai-Yuan Pan
A novel double-hydrophilic block copolymer P(MEO 2 MA- co -OEGMA)- b -PAMA has been successfully synthesized by two-step RAFT polymerization. Then, the amino groups of PAMA blocks in the copolymers react with 1-pyrenecarboxaldehyde via a “Schiff-base” reaction, and the resulting copolymers are self-assembled to form spherical micelles in aqueous solution. Because the “Schiff-base” linkage is pH sensitive, the release rate of pyrene depends upon the pH of solution. Complete release is achieved at pH 1, and the control release is much faster at pH 5.5 than that at pH 7.4. With progress of pyrene release, the micelles are disassembled gradually and disappeared completely at last. This double-hydrophilic copolymer is a promising candidate of drug carrier for the aldehyde- containing hydrophobic drugs.
研究领域:
高分子化学
·
药剂学
·
纳米医学
·
生物材料
·
药物递送系统
✓ 已验证
DOI
高影响因子
JOURNAL OF MATERIALS CHEMISTRY
·
2011
·Vol. 21
·期 40
·16028-16034
·
IF 5.101
Jun Shi,Zhengzheng Zhang,Gefei Li,Shaokui Cao
Alginate/CaCO3 hybrid beads with pH- and thermal-responsive drug release properties were prepared under compressed CO2 using aliphatic poly(urethane-amine)s (PU) as the thermal-responsive component. Polyacrylic acid (PAA) was used as a crystal growth additive to control the structure of the hybrid beads. The hybrid beads were characterized by using scanning electron microscopy, X-ray powder diffraction and thermogravimetric analysis. The interaction between PAA and aliphatic PU contributed to the formation of alginate beads with a compact CaCO3 shell. Indomethacin release behaviour was found to be pH- and thermal-responsive. The release profiles were sustained with CaCO3 microparticles, indicating that the compact CaCO3 shell could hinder the permeability of the encapsulated drug and reduce the drug release effectively. The results suggest that the hybrid alginate beads can be used as “smart” polysaccharide materials for sustained dual-responsive drug delivery.
研究领域:
生物材料
·
药物递送系统
·
高分子科学
·
纳米医学
·
药剂学
·
生物化学
·
组织工程
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）