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RSC Advances · 2015 ·Vol. 5 ·期 30 ·23181-23188 · IF 3.84

Controllable microfluidic fabrication of Janus and microcapsule particles for drug delivery applications

Wenxiu Li,Hua Dong,Guannan Tang,Ting Ma,Xiaodong Cao

Janus and microcapsule particles are very attractive for drug delivery applications due to their capability of targeted and/or programmed drug release. In this paper, a facile yet robust strategy is reported for the first time to fabricate both Janus and microcapsule particles in a simple microfluidic device via the same protocol. According to the classic spreading and partial wetting theory, the key point to fabricate Janus and microcapsule particles in single emulsions is that the two immiscible components should undergo a precisely controlled phase separation, i.e., dewetting for Janus particles and wetting for microcapsule particles. Herein we show that this requirement can be satisfied simply by a subtle choice of organic solvents for the dispersed phase. As a model hybrid material, PLGA/PCL Janus and microcapsule particles are obtained via switching the organic solvent between dimethyl carbonate and dichloromethane. ATR-FTIR spectra and acetone treatment demonstrate that PLGA and PCL occupy their own hemisphere in the Janus particles. In contrast, the shell on the microcapsule particle surface is composed of only PLGA, and the core is composed of PCL in which tiny PLGA beads are embedded. The applications of PLGA/PCL Janus and microcapsule particles in drug delivery are characterized via an in vitro degradation test. The results prove that Janus and microcapsule particles exhibit distinct degradation behaviors, implying their capability of programmable drug delivery in different manners.

研究领域: 生物医学工程 · 制药科学 · 材料科学
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Frontiers in Pharmacology · 2024 · IF 4.4

A novel functionally graded bilayer membrane with excellent barrier function and in vivo osteogenesis promotion for guided bone regeneration

Li Junxuan,Ding Jiaxin,Zhou Tao,Li Bolun,Wang Jingjing,Wang Hanchi,Fu Li

Introduction: Guided bone regeneration (GBR) technology has been widely used as a reliable method to address alveolar bone defects. To improve the clinical effects of GBR approach, there have been attempts to develop barrier membranes with enhanced regenerative properties. However, modifying the material and structure of GBR membranes to integrate physicochemical properties and biological activity remains challenging. The aim of this study was to develop a novel functionally graded bilayer membrane (FGBM) with a gradient structure and composition, and to evaluate its osteogenesis promotion effect for GBR.Methods: By combining the phase inversion method and electrospinning method, functionally graded bilayer membranes (FGBM) with gradient structure and composition of poly(lactic-co-glycolic acid) (PLGA), nano-hydroxyapatite (nHA), and gelatin were fabricated in this study. The physicochemical and biological properties of the prepared FGBM, including structural and morphological characterization, mechanical properties, in vitro biodegradation, cell behaviors, and in vivo osteogenic bioactivity, were comprehensively evaluated.Results: The findings demonstrated the successful fabrication of PLGA/nHA/gelatin FGBM with an asymmetric structure, exhibiting enhanced hydrophilic, mechanical, and degradation properties. The incorporation of gelatin not only improved the biological integration, but also enhanced the binding affinity between electrospun fiber layer and phase inversion layer. The FGBM with a 30% nHA mass fraction and a PLGA/gelatin mass ratio of 1:1 exhibited excellent barrier function and osteogenic bioactivities in vitro and in vivo.Discussion: This work demonstrated the potential of PLGA/nHA/gelatin FGBM in bone regeneration and provided valuable insight for the development of barrier membrane.

研究领域: 生物材料学 · 口腔医学 · 组织工程学
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Small · 2024 · IF 13

Development of Stable and Intensified Mixing Processes for the Precise and Scalable Production of Uniform Drug Delivery Nanocarriers

Meng Cao,Yunfeng Zeng,Xianglin Liu,Yue Liu,Cheng Chen,Lingxi Guo,Haiping Zheng,Haixia Shen,Yongzhong Yao,Jing Zhang,Ziyi Yu

Nanocarriers show great promise in drug delivery but face challenges in stability, uniformity, and morphology control. This work introduces an enhanced mixing process to overcome these obstacles, specifically aiming to produce consistently sized poly(lactic-co-glycolic) acid (PLGA) nanoparticles loaded with anti-tumor drugs. By innovatively integrating a pulsation dampener into the microfluidic channels of a continuous flow preparation system, the flow stability of piston pumps is improved nearly tenfold. Consequently, large-scale production of uniformly sized nanoparticles with customizable dimensions is achieved through nanoprecipitation. Furthermore, incorporating terminal double-bond-functionalized poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-maleimide (PLGA-PEG-Mal) enables these nanoparticles to act as nano-crosslinkers. This facilitates in situ crosslinking with thiolated hyaluronic acid via a spontaneous thiol-ene coupling reaction under physiological conditions, allowing for minimally invasive drug administration and significantly enhancing localized drug retention. The material's degradability in the presence of endogenous enzymes ensures controlled drug release, as demonstrated with the anti-tumor drug doxorubicin (DOX). Validation in a murine breast cancer model shows reduced toxicity and a substantial reduction in tumor weight compared to the free DOX group. These findings confirm the approach's effectiveness for breast cancer treatment and pave the way for innovative solutions in nanomedicine, providing a practical microfluidic mixing system for the design and large-scale production of nanomedicines.

研究领域: 药学 · 生物医学工程 · 纳米医学
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Antibiotics-Basel · 2024 ·Vol. 13 ·期 3 ·228 · IF 4.3

Polylactic Glycolic Acid-Mediated Delivery of Plectasin Derivative NZ2114 in Staphylococcus epidermidis Biofilms

Xuanxuan Ma,Na Yang,Ruoyu Mao,Ya Hao,Da Teng,Yinhua Huang,Jianhua Wang

Antimicrobial peptides (AMPs) are antibiotic candidates; however, their instability and protease susceptibility limit clinical applications. In this study, the polylactic acid–glycolic acid (PLGA)–polyvinyl alcohol (PVA) drug delivery system was screened by orthogonal design using the double emulsion–solvent evaporation method. NZ2114 nanoparticles (NZ2114-NPs) displayed favorable physicochemical properties with a particle size of 178.11 ± 5.23 nm, polydispersity index (PDI) of 0.108 ± 0.10, ζ potential of 4.78 ± 0.67 mV, actual drug-loading rate of 4.07 ± 0.37%, encapsulation rate of 81.46 ± 7.42% and cumulative release rate of 67.75% (120 h) in PBS. The results showed that PLGA encapsulation increased HaCaT cell viability by 20%, peptide retention in 50% serum by 24.12%, and trypsin tolerance by 4.24-fold. Meanwhile, in vitro antimicrobial assays showed that NZ2114-NPs had high inhibitory activity againstStaphylococcus epidermidis(S. epidermidis) (4–8 μg/mL). Colony counting and confocal laser scanning microscopy (CLSM) confirmed that NZ2114-NPs were effective in reducing the biofilm thickness and bacterial population ofS. epidermidisG4 with a 99% bactericidal rate of persister bacteria, which was significantly better than that of free NZ2114. In conclusion, the results demonstrated that PLGA nanoparticles can be used as a reliable NZ2114 delivery system for the treatment of biofilm infections caused byS. epidermidis.

CAS / MDL: 9002-89-5
研究领域: 药学 · 微生物学 · 材料科学
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Nanoscale · 2020 ·Vol. 12 ·期 19 ·10623-10638 · IF 6.895

Multiple targeting strategies achieve novel protein drug delivery into proapoptosis lung cancer cells by precisely inhibiting survivin

Fabiao Hu,Ting Yan,Wei Guo,Qiuli Liu,Myong Hun Han,Chang Liu,Yuping Liu,Wenyun Zheng,Fang You,Yi Yang,Wenliang Zhang,Xingyuan Ma

Therapeutic recombinant proteins have numerous advantages and benefits over chemical drugs, particularly high specificity and good biocompatibility. However, the therapeutic potential and clinical application of current anticancer protein drugs are limited as most biomarkers are located within cells, and multiple physiological barriers exist between the point of administration and the intracellular biomarker. Herein, we report a novel strategy to accurately deliver a cell-permeable dominant-negative TATm-Survivin (TmSm) protein (T34A) to intracellular survivin in cancer cells by overcoming multiple barriers in vivo. A poly(D,L-lactide-co-glycolide) (PLGA) inner core, a polyethylene glycol (PEG) modification, and a TATm peptide were simultaneously introduced to mediate tumor tissue targeting and response to pH-triggered TmSm release. Compared to free TmSm, the PEGylated-PLGA nanoparticle platform achieved a significantly higher cellular uptake efficiency (1.79-fold for A549 and 1.77-fold for Capan-2), effectively decreased IC50 (1.22-fold for A549 and 1.17-fold for Capan-2), and largely elevated apoptosis in different cancer cells (1.17-fold for A549 and 1.15-fold for Capan-2). Besides, this newly developed nanoplatform showed increased protein drug accumulation in the tumor site in A549-bearing nude mice and reached a tumor inhibition rate of 55.81% (1.35-fold versus free TmSm) by reducing the expression of intracellular survivin. All these results confirmed that our newly developed delivery strategy is a very promising tool, which helps protein drugs to cross multiple barriers in vivo and achieves precise targeting to intracellular biomarkers. This strategy could also be applied to other types of protein drugs to further improve their clinical anticancer therapeutic efficacy.

CAS / MDL: 9002-89-5 298-93-1
研究领域: 肿瘤学 · 药剂学 · 分子生物学
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CURRENT PHARMACEUTICAL DESIGN · 2023 ·Vol. 29 ·期 9 ·686-696 · IF 3.1

Preparation and Characterization of PLGA-based Magnetic Polymer Nanoparticles for Targeting Pancreatic Adenocarcinoma

Lu Liangji,Jie Liyong,Zhou Ying,Zhang Jiaojiao,Feng Tingting,Zhu Yue,Chen Teng,Zhu Xiuliang,Ji Jiansong,Wang Zuhua

This study aims to develop a novel tumor-targeted molecular probe for pancreatic cancer imaging. The objective of this is to prepare a CKAAKN peptide-conjugated poly (lactic-co-glycolic acid)-poly (ethylene glycol) amphiphilic polymer (CKAAKN-PEG-PLGA) for the tumor-targeted delivery of magnetic resonance imaging (MRI) contrast agent ultrasmall superparamagnetic iron oxide (USPIO). Background: The early diagnosis of pancreatic cancer is crucial for improving its prognosis, but the clinical application of many diagnostic methods is limited owing to a lack of specificity and sensitivity. Methods: CKAAKN-PEG-PLGA was synthesized by the amidation reaction. USPIO-loaded polymeric magnetic nanoparticles (USPIO@CKAAKN-PEG-PLGA) were prepared by the emulsion solvent evaporation method. The in vitro tumor targeting and bio-safety of nanoparticles were evaluated by targeted cellular uptake, MR imaging and MTT assay. Results: USPIO@CKAAKN-PEG-PLGA nanoparticles showed excellent biosafety with an average diameter of 104.5 ± 4.1 nm. Modification of CKAAKN peptide could improve USPIO binding ability to internalize into CKAAKN-positive BxPC-3 cells compared with non-targeting nanoparticles and the control group. The relative fluorescence intensity in BxPC-3 and HPDE6-C7 cells was 23.77 ± 4.18 and 6.44 ± 2.10 (p < 0.01), and respectively became 16.13 ± 0.83 and 11.74 ± 1.74 after the addition of free CKAAKN peptide. In vitro MR imaging studies showed that an obvious decrease in the signal intensity was observed in the targeted nanoparticles group incubated with BxPC-3 and HPDE6-C7 cells (p < 0.05). Conclusion: USPIO@CKAAKN-PEG-PLGA nanoparticles could significantly enhance the tumor specificity of USPIO in CKAAKN-positive pancreatic cancer cell BxPC-3, which is expected as a promising candidate of MRI contrast enhancement for the early diagnosis of pancreatic cancer.

研究领域: 纳米技术 · 癌症研究 · 生物医学工程 · 材料科学 · 医学成像
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2012 · IF 3.456

Electrospun Chitosan-graft-PLGA nanofibres with significantly enhanced hydrophilicity and improved mechanical property

Ai.D. Li,Z.Z. Sun,M. Zhou,X.X. Xu,J.Y. Ma,W. Zheng,H.M. Zhou,L. Li,Y.F. Zheng

This work reported a novel poly(lactic-co-glycolic acid) (PLGA) composite nanofibres, Chitosan-graft-PLGA (CS-graft-PLGA), produced by the electrospinning technique. CS was grafted onto the PLGA surface via the cross-linking agents reacting with the PLGA with reactive carboxyl groups on its surfaces introduced from the alkali treatment. The CS grafting ratios of the electrospun CS-graft-PLGA nanofibres were about 2.43%, 4.34%, 16.97% and 39.4% after cross-linked for 12   h, 16   h, 20   h and 24   h, respectively. The electrospun CS-graft-PLGA nanofibres were significantly uniform and highly smooth without the occurrence of bead defects, even at high CS grafting ratio. The electrospun CS-graft-PLGA nanofibres not only possessed the improved hydrophilicity and the protein absorption property, but also maintained the good mechanical property. In addition, the CS grafting can be conducive to accelerate degradation rate of PLGA.

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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS · 2026 · IF 4.3

Cardiac Homing Peptide-Decorated Epigallocatechin Gallate-Loaded PLGA Nanoparticles Alleviate Acute Myocardial Infarction

Haiqi Li,Ruohui Huang,Jinhong Zhang,Dongli Jiang,Jie Jian

Epigallocatechin gallate (EGCG) exerts cardioprotective effects on acute myocardial infarction (AMI) through multiple pathways. However, the clinical application of EGCG is limited because of its instability under physiological conditions and low bioavailability. In this study, poly (lactic-co-glycolic acid) (PLGA) was used as a drug carrier to prepare EGCG nanoparticles, then EGCG targeting drug delivery system was designed modifying by cardiac homing peptide (CHP).We constructed a preparation route combining double-emulsion solvent evaporation method and carbodiimide method. By optimizing the preparation process, the particle size of EGCG nanoparticle was reduced and the dispersibility was improved. In addition, the established preparation procedure uses safe and low-toxicity reagents, requires no strict temperature control or specialized instrumentation, and therefore significantly reduces the technical difficulty of large-scale industrial production. EGCG-PLGA-CHP had myocardial targeting and good safety in the MTT cytotoxicity test, as well as alleviated AMI by regulating apoptosis-related protein expression in a dose-dependent manner. Compared with EGCG monomer, EGCG-PLGA-CHP achieved a better therapeutic effect. This study provides a new strategy for promoting the application of EGCG in the clinical treatment of AMI.

CAS / MDL: 25952-53-8 9003-11-6
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ADVANCED FUNCTIONAL MATERIALS · 2026 · IF 19.9

Beyond Material Dominance: A Coevolutionary Approach to the “Real” IVIVC of PLGA Microspheres

Shan Wang,Yabing Hua,Jijun Yu,Xudong Dai,Yuhua Ran,Wenpeng Zhang,Yanan Zhai,Zhiping Li,Xiaomei Zhuang,Jing Gao

Thorough understanding and accurate prediction of in vivo drug release are essential for developing long-acting microsphere systems. However, the fate of microspheres after prolonged tissue residence and the regulatory role of physiological factors remain unclear, hindering elucidation of release mechanisms. Herein, the dynamic evolution of microsphere depots and associated microenvironmental changes were studied. Beyond poly(lactic-co-glycolic acid) (PLGA) and API effects, microsphere depot behavior is partly regulated by conserved biological processes, with skeletal muscle and subcutaneous tissue employing distinct adaptive strategies to restore homeostasis. Using these insights, we developed the in vivo release predictive models (IVRPMs) that establish a true IVIVC for naltrexone PLGA microspheres. The IVRPMs demonstrated broad applicability across microspheres with different APIs and PLGA types, and showed promising translational potential in beagle and human studies. This study shifts the research paradigm from “material-dominated release” to “organism-material coevolution”, addressing a key question in depot formulation fate.

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iScience · 2026 · IF 4.5

Oral Milk Exosome-PLGA Nanoparticles Enhance Anti-Tuberculosis Efficacy of PBTZ169 and Bedaquiline

Eryue Liu,Chennan Liu,Yangxue Ye,Zimo Wang,Weiyan Zhang,Lei Fu,Bin Wang,Yujin Wang,Yu Lu

The oral delivery of next-generation anti-tuberculosis drugs, such as PBTZ169 and bedaquiline, is hindered by poor solubility and low bioavailability. We have developed a bioinspired delivery platform that combines milk exosomes with PLGA nanoparticles to deliver the two drugs separately. This nano-delivery system leverages the gastrointestinal stability and mucosal penetration of exosomes, along with the high encapsulation efficiency of PLGA, significantly enhancing drug hydrophilicity and stability. In murine models, the exosome-coated nanoparticles increased plasma bioavailability by 2.5–4.9-fold compared to free drugs and achieved superior accumulation in target organs, while mitigating the cardiotoxicity risk associated with BDQ. This synergistic strategy, integrating synthetic and natural carriers, overcomes key pharmacological barriers, offering a promising approach to developing effective and patient-compliant oral therapies for tuberculosis and potentially other infectious diseases.

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ACS Biomaterials Science & Engineering · 2026 · IF 6

Polydopamine-Functionalized HMS/PLGA Composite Microsphere Scaffold Modulates Enhances Immunomodulation and Bone Repair

Zhenyu Wen,Qiping Huang,Qian Du,Qinghong Fan,Qianyu Xie,Yuanhao Lv,Jun Chen,Weikang Xu,Qingde Wa

The development of poly(lactic-co-glycolic acid) (PLGA)-based microsphere scaffolds with comprehensive osteogenic activity, hydrophilicity, mechanical strength, and biocompatibility remains a significant challenge. Here, we constructed a hexagonal mesoporous silica (HMS)/PLGA composite microsphere scaffold (HP). Subsequently, we further developed a polydopamine (PDA)-modified version of HP (PHP) by applying a PDA coating to its surface. Compared with HP, PHP exhibited improved compressive strength and hydrophilicity while maintaining desirable porosity. In vitro, PHP promoted BMSCs proliferation and osteogenic differentiation, upregulated osteogenic gene expression, and induced macrophage polarization toward the M2 anti-inflammatory phenotype. In a rat calvarial defect model, PHP significantly enhanced bone regeneration, as confirmed by micro-CT and histological analyses, and maintained elevated expression of BMP-2 and VEGF to support osteogenesis and angiogenesis. Immunostaining further demonstrated increased CD163 and decreased iNOS expression, indicating an immunomodulatory effect. All materials showed favorable biocompatibility. This work integrated the surface functionalization of PDA with the structural features of HMS, demonstrating that the ternary composite scaffold achieved simultaneous regulation of the immune microenvironment and osteogenesis, providing a promising strategy for clinically translatable bone repair materials.

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Regenerative Therapy · 2026 · IF 4

3D-printing flexible PLGA scaffold modified with bioorthogonal IGF-1 for skin regeneration

Yi Zhang,Qi Fang,Xiao Yang

Introduction 3D-printing implants have attracted increasing attention for enhancing the regeneration of various wound types. The rigidity of traditional 3D printing materials limits their applicability in skin wound repair. In addition, improving the bioactivity of polymeric materials remains an urgent challenge to be addressed. Insulin-like growth factor-1 (IGF-1) is widely recognized for its efficacy in skin wound repair. However, the potency of IGF-1 in wound regeneration is limited by its unstable binding to the implants. Methods In this study, A phase inversion-based deposition modeling 3D printing technique was employed to construct flexible poly(lactic-co-glycolic acid) (PLGA) scaffold. Additionally, a novel 3D-printing flexible skin implantation functionalized with bioorthogonal IGF-1 (DA-IGF-1) was fabricated. The adhesion, proliferation and relative mRNA expression of cells on PLGA scaffold were assessed. Meanwhile, a full-thickness skin defect regeneration model was established on the rat back to evaluate the wound repair efficacy of the implanted scaffolds. Results The DA-IGF-1 exhibited outstanding binding ability on the scaffold. The resulting PLGA flexible scaffold modified with DA-IGF-1 showed significantly enhanced hydrophilicity and biocompatibility compared with the control group materials ( p  < 0.05). The expression of wound regeneration related genes was also upregulated significantly in the DA-IGF-1 group ( p  < 0.05). In vivo study indicated that bioactive implants effectively promoted healing and neovascularization of full-thickness skin defects in rats. Conclusion These results demonstrated that the 3D-printing flexible PLGA scaffold modified with bioorthogonal IGF-1 holds great potential for application as a novel therapeutic strategy for wound regeneration.

CAS / MDL: 872-50-4
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