DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
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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
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药物化学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
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2017
·Vol. 12
·期 6
·580-585
·
IF 0
Shijie Wei,Jingbo Ren,Ning Li,Wuzhen Huo,Chongkai Gao
An LCC delivery system for Fenofibrate (Fen) was developed to improve its poorly oral bioavailability. Fen-LCC preparation methods were screened, and the prepared Fen-LCC was then characterized by a polarizing microscope and transmission electron microscopy (TEM). The spray drying technique was selected to dry and solidify particles into powder. The in vitro release of Fen-LCC was measured and in vivo pharmacokinetic experiments were carried out on rats after oral administration. Particles prepared through the high-temperature input method exhibited structural characteristics of LCC, and re-dissolved particles maintained the same features. The LCC delivery system can significantly improve in vitro release outcomes. After oral administration, AUCs of the suspension and LCC systems were measured at 131.6853 µg⋅h/ml and 1435.72893 µg⋅h/ml, respectively. The spray drying process presented here better maintains cubic structures, and the LCC system significantly improves bioavailability levels.
研究领域:
药剂学
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药物递送系统
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纳米医学
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药代动力学
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药物代谢
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DOI
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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2017
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IF 3.756
Yu Huang,Jin-Mei Li,Zhi-Hui Lai,Jun Wu,Tong-Bu Lu,Jia-Mei Chen
Both cocrystal and nanocrystal technologies have been widely used in the pharmaceutical development for poorly soluble drugs. However, the synergistic effects due to the integration of these two technologies have not been well investigated. The aim of this study is to develop a nano-sized cocrystal of phenazopyridine (PAP) with phthalimide (PI) to enhance the release rate and oral bioavailability of PAP. A PAP–PI nano-cocrystal with particle diameter of 21.4 ± 0.1 nm was successfully prepared via a sonochemical approach and characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and dynamic light scattering (DLS) analysis. An in vitro release study revealed a significant release rate enhancement for PAP–PI nano-cocrystal as compared to PAP–PI cocrystal and PAP hydrochloride salt. Further, a comparative oral bioavailability study in rats indicated significant improvement in C max and oral bioavailability (AUC 0 − ∞ ) by 1.39- and 2.44-fold, respectively. This study demonstrated that this novel nano-cocrystal technology can be a new promising option to improve release rate and absorption of poorly soluble compounds in the pharmaceutical industry.
研究领域:
药剂学
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药物递送
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纳米医学
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药物代谢
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晶体工程
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DOI
高影响因子
Evidence-based Complementary and Alternative Medicine
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2015
·Vol. 2015
·期 1
·239749
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IF 1.88
Zhiping Wang,Junbiao Wu,Qun Zhou,Yifei Wang,Tongsheng Chen
Berberine (Ber), an isoquinoline derivative alkaloid and active ingredient of Coptis, has been demonstrated to possess antidiabetic activities. However its low oral bioavailability restricts its clinical application. In this report, Ber nanosuspension (Ber-NS) composed of Ber and D- α -tocopheryl polyethylene glycol 1000 succinate (TPGS) was prepared by high pressure homogenization technique. Antidiabetic effects of Ber-NS relative to efficacy of bulk Ber were evaluated in streptozotocin (STZ) induced diabetic C57BL/6 mice. The particle size and zeta potential of Ber-NS were 73.1 ± 3.7 nm and 6.99 ± 0.17 mV, respectively. Ber-NS (50 mg/kg) treatment via oral gavage for 8 weeks resulted in a superior hypoglycemic and total cholesterol (TC) and body weight reduction effects compared to an equivalent dose of bulk Ber and metformin (Met, 300 mg/kg). These data indicate that a low dosage Ber-NS decreases blood glucose and improves lipid metabolism in type 2 diabetic C57BL/6 mice. These results suggest that the delivery of Ber as a nanosuspension is a promising approach for treating type 2 diabetes.
研究领域:
药剂学
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药理学
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分子药理学
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药物递送系统
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糖尿病研究
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药物代谢
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纳米医学
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DOI
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
·
2021
·Vol. 46
·期 1
·e14007
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IF 2.72
Jing Liu,Zhongan Zhu,Yuhang Yang,Michael Adu-Frimpong,Lin Chen,Hao Ji,Elmurat Toreniyazov,Qilong Wang,Jiangnan Yu,Ximing Xu
A liposome of Licochalcone A (LCA-Liposomes) was purposively prepared to ameliorate the low in vivo availability and efficacy of LCA. Physical characterization of LCA-Liposomes was carried out mainly by determining particle size, morphology, zeta potential (Z-potential), and efficiency of LCA encapsulation (EE) via appropriate techniques. Also, the rate of LCA release in vitro and distribution in vivo (plasma and tissues) was evaluated. Evaluation of the antirenal activity of LCA-liposomes was carried out by establishing chronic renal failure (CRF) model in mice through intragastric administration of adenine (200 mg/kg) and subsequent determination of biochemical parameters and examination of tissue sections. Respectively, the mean size of liposomal particles, Z-potential and EE of LCA-Liposomes were 71.78 ± 0.99 nm, −38.49 ± 0.06 mV, and 97.67 ± 1.72%. Pharmacokinetic and tissue distribution studies showed that LCA-Liposomes could improve the availability of LCA in the blood and tissues, whereas during pharmacodynamics studies, the liposome effectively improved the therapeutic effect of LCA on CRF mice by potentially protecting the renal tissues while exhibiting antioxidant activity. In conclusion, LCA-Liposomes could effectively improve the bioavailability of LCA and provide platform for the development of LCA-related functional products. Practical applications As a traditional Chinese medicine, licorice is widely used in food and pharmaceutical industries. LCA is a small molecule flavonoid extracted from the root of licorice. In this study, LCA was loaded on liposome carriers, which significantly improved the water solubility and oral bioavailability, and proved that LCA-Liposomes have certain therapeutic effects on chronic renal failure, thereby providing a basis for the development of LCA into drugs or functional food in the future.
研究领域:
药剂学
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药理学
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分子药理学
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药物代谢
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纳米医学
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中药药理学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2013
·
IF 3.458
Ziwei Zhang,Xiaole Qi,Xiangbo Li,Jiayu Xing,Xuehua Zhu,Zhenghong Wu
Multilayer-coating technology is the traditional method to achieve pulsatile drug release with the drawbacks of time consuming, more materials demanding and lack of efficiency. The purpose of this study was to design a novel pulsatile drug delivery system based on the physiochemical interaction between acrylic copolymer and organic acid with relatively simpler formulation and manufacturing process. The Enalapril Maleate (EM) pulsatile release pellets were prepared using extruding granulation, spheronization and fluid-bed coating technology. The ion-exchange experiment, hydration study and determination of glass transition temperature were conducted to explore the related drug release mechanism. Bioavailability experiment was carried out by administering the pulsatile release pellets to rats compared with marketed rapid release tablets Yisu ® . An obvious 4 h lag time period and rapid drug release was observed from in vitro dissolution profiles. The release mechanism was a combination of both disassociated and undisassociated forms of succinic acid physiochemically interacting with Eudragit ® RS. The AUC0-τ of the EM pulsatile pellets and the market tablets was 702.384 ± 96.891 h ng/mL and 810.817 ± 67.712 h ng/mL, while the relative bioavailability was 86.62%. These studies demonstrate this novel pulsatile release concept may be a promising strategy for oral pulsatile delivery system.
研究领域:
药剂学
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药物递送
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生物药剂学
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药物代谢
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制剂工程
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药动学
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DOI
高影响因子
AAPS PHARMSCITECH
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2019
·Vol. 20
·期 1
·1-14
·
IF 2.608
Wang Xingqi,Zhang Yong,Huang Jie,Tian Chunling,Xia Mengqiu,Liu Liu,Li Zhengguang,Cao Jiaojiao,Gui Shuangying,Chu Xiaoqin
The purpose of this paper was to investigate the potential of liquid crystalline (LC) gels for ophthalmic delivery, so as to enhance the bioavailability of pilocarpine nitrate (PN). The gels were prepared by a vortex method using phytantriol and water (in the ratio of 73:27 w / w ). Their inner structures were confirmed by crossed polarized light microscopy, small-angle X-ray scattering, attenuated total reflectance-Fourier transform infrared spectrum, and rheology. The in vitro release studies revealed that PN could keep sustained release from the gels over a period of 12 h. The ex vivo apparent permeability coefficient of the gels demonstrated a 3.83-folds ( P < 0.05) increase compared with that of eye drops. The corneal hydration levels of the gel maintained in the normal range of 79.46 ± 2.82%, hinting that the gel could be considered non-damaging and safe to the eyes. Furthermore, in vivo residence time evaluation suggested that a better retention performance of LC gel was observed in rabbit’s eyes compared to eye drops. In vivo ocular irritation study indicated that LC gel was nonirritant and might be suitable for various eye applications. In conclusion, LC gels might represent a potential ophthalmic delivery strategy to overcome the limitations of eye drops.
研究领域:
药剂学
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药物递送系统
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眼科学
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
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2019
·
IF 5.399
Meng Shi,Dan-Yang Ying,Mya Myintzu Hlaing,Jian-Hui Ye,Luz Sanguansri,Mary Ann Augustin
Novel delivery systems for epigallocatechin gallate (EGCG) were developed using broccoli by-products and their fractions as carriers. Puree and pomace from broccoli by-products had higher adsorption capacities for EGCG than juice at 25 °C (43.20 mg g −1 , 39.47 mg g −1 and 25.22 mg g −1 dry weight for pomace, puree and juice respectively). Chemical sorption is the rate-controlling step for EGCG-broccoli interactions. Langmuir and Freundlich models well described the adsorption of EGCG onto puree and pomace. FTIR results indicated that EGCG-puree had stronger interaction than EGCG-pomace. When the same level of EGCG (∼26 mg) was added to different matrices, more EGCG (∼20%) was recovered from the in vitro digestion system of EGCG-loaded puree than from the EGCG-loaded pomace (14%) and neat EGCG (9%). The antioxidant capacity of the whole digesta was positively correlated with the EGCG levels. Broccoli by-products are promising carriers for delivering and stabilizing EGCG through gastrointestinal digestion.
研究领域:
食品科学
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营养学
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天然产物化学
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药物递送
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生物利用度
·
分子互作
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）