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AAPS PHARMSCITECH · 2019 ·Vol. 20 ·期 8 ·1-13 · IF 2.608

Development, Optimization, and Evaluation In Vitro/In Vivo of Oral Liquid System for Synchronized Sustained Release of Levodopa/Benserazide

Qu Yang,Lai Wen-Long,Xin Yuan-Rong,Zhu Fei-Qin,Zhu Yuan,Wang Li,Ding Yue-ping,Xu Ying,Liu Hong-Fei

To enhance efficiency, convenience, and safety of Parkinson’s disease (PD) treatment for geriatric patients, an advanced suspension of Levodopa/Benserazide hydrochloride (LD/BH) has been prepared by cation-exchange resin and used to synchronize sustained release of LD and BH by optimizing coating parameters and prescription. For the purpose, LD and BH were immobilized on the surface of cation-exchange resin, respectively. Based on HPLC results, the cation-exchange resin showed high loading capacity. The studies on drug loading mechanism indicated that both drugs were immobilized by electrostatic interaction rather than physical adsorption. After PEG modification, pretreated drug-resin complexes were coated by emulsion–solvent evaporation method. In order to control drug release in a sustained manner, coating parameters of drug-resin microcapsules were optimized respectively by single-factor analysis. Further, coating prescription of the microcapsules was optimized to synchronize sustained release of LD and BH in vitro by orthogonal design. Utilizing optimal LD-resin microcapsules and BH-resin microcapsules, LD/BH suspension, containing both of them, was prepared by an optimal formulation and characterized by accelerated test and pharmacokinetic study in vivo . The accelerated test confirmed high stability of LD/BH suspension. According to pharmacokinetic results in vivo , in contrast with LD/BH commercial tablets, LD/BH suspensions did not only synchronize sustained release of both drugs but also show good bioequivalence. As LD/BH sustained release suspension can synchronize sustained release of multiple active ingredients by oral administration, the suspension presents promising oral dosage forms for geriatric patients with PD. An advanced Levodopa/Benserazide hydrochloride (LD/BH) suspension, prepared by cation-exchange resin and optimized microencapsulation, synchronizes sustained releases of LD and BH in vivo to benefit Parkinson’s disease treatment for geriatric patients.

研究领域: 药剂学 · 神经病学
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ACS Biomaterials Science & Engineering · 2022 · IF 5.395

Hydrogel Microencapsulation Enhances Cryopreservation of Red Blood Cells with Trehalose

Jianbo Yao,Lingxiao Shen,Zhongrong Chen,Bing Zhang,Gang Zhao

Cryopreservation of red blood cells (RBCs) plays a vital role in preserving rare blood and serologic testing, which is essential for clinical transfusion medicine. The main difficulties of the current cryopreservation technique are the high glycerol concentration and the tedious deglycerolization procedure after thawing. In this study, we explored a microencapsulation method for cryopreservation. RBC–hydrogel microcapsules with a diameter of approximately 2.184 ± 0.061 mm were generated by an electrostatic spraying device. Then, 0.7 M trehalose was used as a cryoprotective agent (CPA), and microcapsules were adhered to a stainless steel grid for liquid nitrogen freezing. The results show that compared with the RBCs frozen by cryovials, the recovery of RBCs after microencapsulation is significantly improved, up to a maximum of more than 85%. Additionally, the washing process can be completed using only 0.9% NaCl. After washing, the RBCs maintained their morphology and adenosine 5′-triphosphate (ATP) levels and met clinical transfusion standards. The microencapsulation method provides a promising, referenceable, and more practical strategy for future clinical transfusion medicine.

CAS / MDL: 9005-38-3
研究领域: 生物医学工程 · 血液学 · 输血医学
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INTERNATIONAL JOURNAL OF DAIRY TECHNOLOGY · 2022 ·Vol. 75 ·期 3 ·513-526 · IF 4.286

Effects of soy lecithin concentration on the physicochemical properties of whey protein isolate, casein-stabilised simulated infant formula emulsion and their corresponding microcapsules

Feiyang Wu,Fang Chen,Yizhen Pu,Fang Qian,Youbin Leng,Guangqing Mu,Xuemei Zhu

The effects of soy lecithin (SL) concentration on the physicochemical properties of whey protein isolate, casein-stabilised simulated infant formula emulsion (SIFE) and the corresponding microcapsules obtained by spray-drying were investigated. Soy lecithin addition significantly reduced the apparent viscosity of SIFE. Among the emulsions investigated in this work, the sample prepared with 5% SL demonstrated the smallest average particle size, largest intermolecular repulsion, lowest creaming index and strongest antioxidant capacity. The microcapsule preparations exhibited good re-dispersibility in water. Spectral shifts in the bands of amides I and II indicated that SL addition can effectively enhance the inter- or intramolecular forces of the microcapsules. The high microencapsulation efficiency of 94.03% of the sample prepared with 5% SL could be attributed to favourable interactions between the emulsifier and protein at the adsorption layer. These findings will aid in the development of microcapsules with desirable features from protein–SL mixed systems.

研究领域: 食品科学 · 化学工程 · 营养学
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FOOD CHEMISTRY · 2019 · IF 5.399

Protein-polysaccharide complex coated W/O/W emulsion as secondary microcapsule for hydrophilic arbutin and hydrophobic coumaric acid

Hao Huang,Tarun Belwal,Halah Aalim,Li Li,Xingyu Lin,Songbai Liu,Caixia Ma,Qunhe Li,Ying Zou,Zisheng Luo

This study aimed to examine the modification effect of whey protein concentrate (WPC), WPC-gum arabic (WPC-GA) or WPC-high methoxyl pectin (WPC-PEC) complex to tailor-modify W/O/W emulsion for secondary microencapsulation of hydrophilic arbutin and hydrophobic coumaric acid. The stability and rheological properties of coated emulsions, encapsulation yield, release and degradation kinetics of arbutin and coumaric acid were investigated. Results revealed that WPC-PEC complex (at the ratio of 1:3) coating W/O/W emulsion exhibited the highest viscosity and stability, with the highest encapsulation yield of 91.08% for arbutin and 80.92% for coumaric acid, respectively. Tighter coating structure of the WPC-PEC complex (1:3) forming a stronger gel network structure was confirmed, accounting for the larger mean particle size of 569.67 nm. Moreover, the WPC-PEC (1:3) coating W/O/W emulsion also showed controlled release of arbutin and coumaric acid in simulated conditions. The k value of degradation kinetics for arbutin (7.99 × 10 −4 at pH = 1.2, 4.19 × 10 −4 at 90 °C and 7.52 × 10 −4 at UV-C treatment) and coumaric acid (5.18 × 10 −4 at pH = 1.2, 3.24 × 10 −4 at 90 °C and 6.90 × 10 −4 at UV-C treatment) indicated low degradation rate. The present study revealed that the WPC-PEC (1:3) coating W/O/W emulsion could provide a better synergistic effect on higher encapsulation yield and stability of arbutin and coumaric acid.

研究领域: 食品科学 · 胶体与表面化学 · 制药技术
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MACROMOLECULAR RAPID COMMUNICATIONS · 2023 · IF 4.6

A Bioartificial Pancreas with “Immune Stealth” And Continuous Oxygen Supply for Islet Transplantation

Yin Zheng,Wenyi Yang,Weisong Gao,Xinge Zhang,Zhongming Wu1,Mo Wang

Transplantation of microencapsulated islet cells remains a promising strategy for the normalization of glucose metabolism control in type 1 diabetes mellitus. However, vigorous host immunologic rejection, fibrotic overgrowth around the microcapsules and poor oxygen supply often lead to graft failure. Herein, a bioartificial pancreas is constructed that incorporates the “stealth effect” based on polyethylene glycol copolymers and the high oxygen-carrying performance of fluorinated nanoparticles. Polycationic poly(L-lysine)-grafted-poly(ethylene glycol) is successfully coated on the surface of alginate microcapsules through electrostatic interaction, which can not only resist fibrinogen adhesion and avoid excessive fibrosis around the microcapsules, but also isolate the host immune system from attacking, achieving a “stealth effect” of microencapsulated islet cells. Furthermore, the co-loading of fluoride-based O 2 nanocarriers gives them enhanced oxygen-carrying and continuous oxygen supply capabilities, thereby effectively prolonging the survival of islet cells. The intracapsular islet cells still display similar cell viability and almost normal insulin secretion function even in long-term culture under hypoxic conditions. Collectively, this work opens up a new approach for microencapsulated islets to efficiently evade host immune attack and improve oxygen supply, and provides a promising strategy for islet transplantation in type 1 diabetes mellitus. This article is protected by copyright. All rights reserved

研究领域: 生物医学工程 · 组织工程 · 糖尿病研究 · 纳米技术 · 免疫学
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JOURNAL OF CONTROLLED RELEASE · 2024 · IF 10.5

Site-specific bioorthogonal regulation of bone morphogenetic protein 2 expression for effective bone regeneration

Yu Sun,Xiuhua Zhang,Wanrong Hong,Yingfeng Qin,Yunan Man,Maolin He,Jin-Wen Liu,Jia Chen

Growth factor holds great promise for bone regeneration, and spatiotemporal control of their expressing through site-specific reactions is crucial but challenging for on-demand therapy. In this study, we present the development of a novel unnatural amino acids (UAAs)-triggered therapeutic switch (UATS) system, composed of an orthogonal aminoacyl-tRNA-synthase (aaRS)-tRNA pair and a bone morphogenetic protein 2 (BMP2) gene harboring premature stop codon, which enable in situ and on-demand initiation of the expression of BMP2. The resulting UATS system allowed specifically control of base expressing on the BMP2 mRNA that switched to the BMP2 protein with complete structure and function to facilitate bone regeneration. Our investigations showed that the UATS system exhibits remarkable attributes of rapid, sensitive, reversible, and sustained BMP2 expression both in vitro and in vivo settings. Moreover, the implantation of microencapsulated cells with UATS system is applied to a mouse femur defect model, demonstrating high effciency in controlled expressing of BMP2 protein and substantial repair of bone defect following oral administration of UAAs. Therefore, our findings underscore the great potential of UATS system for on-demand awakening of functional growth factor, thus offering promising prospects in the realm of regenerative medicine.

CAS / MDL: 6230-11-1
研究领域: 再生医学 · 分子生物学 · 生物医学工程 · 组织工程
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

An injectable and retrievable bioartificial pancreas fabricated by time-sequentially assembling islets-laden microgels for minimally invasive treatment of type 1 diabetes

Weijun He,Haofei Li,Xinbin Xu,Xing Zhang,Junlin Chen,Chuhan Lv,Hongbo Yu,Qi Feng,Hua Dong

Islets transplantation is a promising method to treat type 1 diabetes. Unfortunately, current islet encapsulation and transplantation strategies are difficult to simultaneously achieve the minimally invasive transplantation, rapid mass transportation, accurate positioning, long-term stability and easy retrieval. Herein, we present a novel strategy for islet encapsulation and transplantation that integrates the advantages of microencapsulation and macroencapsulation. Specifically, islets are first encapsulated in methacrylated carboxymethyl chitosan (CMCSMA) microgels by droplet microfluidic technology, and then oxidized sodium alginate-succinimide ester (OSA-NHS) as the assembling agent is added to time-sequentially assemble the islets-laden microgels. The as-formed microgel assembly (MA-CHO/NHS), or namely bioartificial pancreas, is injectable before transplantation due to the quick formation of dynamic Schiff base bonds, and becomes quite stable after transplantation with the slow formation of stable amide bonds. In addition, the interconnected micropores inside the microgel assembly is beneficial for mass transportation, and the abundant aldehyde and succinimide ester groups on assembling agent ensures good tissue adhesion. This injectable, tissue-adhesive, microporous, positionable and retrievable bioartificial pancreas can reverse the blood glucose levels of diabetic mice from hyperglycemia to normoglycemia for at least 90 days, and thus shows a broad application prospect in the field of diabetes treatment.

研究领域: 生物医学工程 · 糖尿病研究 · 组织工程 · 生物材料
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