DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2018
·
IF 1.883
Juan Dai,Wei Long,Zhongping Liang,Lu Wen,Fan Yang,Gang Chen
Delivery of biomacromolecular drugs into the inner ear is challenging, mainly because of their inherent instability as well as physiological and anatomical barriers. Therefore, protein-friendly, hydrogel-based delivery systems following local administration are being developed for inner ear therapy. Herein, biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing interferon α-2 b (IFN α-2 b) were loaded in chitosan/glycerophosphate (CS/GP)-based thermosensitive hydrogel for IFN delivery by intratympanic injection. The injectable hydrogel possessed a physiological pH and formed semi-solid gel at 37 °C, with good swelling and deswelling properties. The CS/GP hydrogel could slowly degrade as visualized by scanning electron microscopy (SEM). The presence of NPs in CS/GP gel largely influenced in vitro drug release. In the guinea pig cochlea, a 1.5- to 3-fold increase in the drug exposure time of NPs-CS/GP was found than those of the solution, NPs and IFN-loaded hydrogel. Most importantly, a prolonged residence time was attained without obvious histological changes in the inner ear. This biodegradable, injectable, and thermosensitive NPs-CS/GP system may allow longer delivery of protein drugs to the inner ear, thus may be a potential novel vehicle for inner ear therapy.
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DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2022
·
IF 5.062
Luyao Huang,Shengjie Wang,Zongning Yin
Therapeutic proteins/peptides face severe stability impairment in biotechnology drug delivery systems prepared by the W/O/W solvent evaporation method. Screening of protein stabilizers for poly (D, l -lactide-co-glycolide) (PLGA) nanoparticles can improve the low encapsulation efficiency and undesirable release behavior of proteins caused by PLGA carriers, which is a crucial step to achieve a high proportion of continuous release of encapsulated protein in the target time and give full play to the therapeutic effect. Therefore, model proteins were selected for stability testing to simulate the specific destabilization pathways. Through the comprehensive study of protein conformation, recovery rate, encapsulation rate, and drug release behavior, the effects of additives on the stability of protein were synthetically characterized, and their action links and mechanisms were also further studied. The results showed that different denaturation environments were intertwined during the preparation and release of peptide-loaded NPs, jointly inducing protein denaturation and incomplete release behavior. After optimization with stabilizers, urea and lactose increased the encapsulation efficiency of proteins to more than 95% (P < 0.001). Except for the P188 , all other stabilizers showed great potential for optimizing the release and stability of the encapsulated protein as a whole, increasing the release proportion of protein from 44% to 60 %-75% (P < 0.0001). The improvement of the drug release curve demonstrated the long-term stabilizing effect of the above-mentioned co-solubilizing additives on the therapeutic protein.
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高影响因子
Frontiers in Bioengineering and Biotechnology
·
2020
·
IF 3.644
Xiang Yang,Wang Weijia,Gao Yuanhui,Zhang Jianquan,Zhang Jing,Bai Zhiming,Zhang Shufang,Yang Yijun
We successfully fabricated artificial bile duct via 3D printing technique which was composed of poly (lactic-co-glycolic acid) (PLGA) and gelatin methacrylate (GelMA). The PLGA-inner layer provided sufficient strength to support the bile duct contraction, the GelMA-outer layer possessed good biocompatibility to provide a good living environment for the cells. Moreover, IKVAV laminin peptide (Ile-Lys-Val-Ala-Val) and ultrasmall superparamagnetic iron oxide (USPIO) were used to regulate scaffold cell adhesion and magnetic resonance imaging (MRI) detection, respectively. After BMSCs co-culture with IKVAV at a certain concentration, the survival rate and adhesion of BMSCs was increased obviously. Meanwhile, the fabricated scaffold exhibited the tensile modulus in the range of 17.19 – 29.05 MPa and the compressive modulus in the range of 0.042 – 0.066 MPa, which could meet the needs of human implantation. In an animal experiment in vivo pig bile duct regeneration, PLGA/GelMA/IKVAV/USPIO duct conduits could promote bile duct regeneration and enhance cytokeratin 19 (CK19) expression. In summary, the composite bile duct scaffold with excellent MRI imaging function and biocompatibility could be used to develop bioactive artificial bile ducts.
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高影响因子
DRUG DELIVERY
·
2020
·
IF 4.902
Minghao Sun,Chune Zhu,Jieyu Long,Chao Lu,Xin Pan,Chuanbin Wu
When antibiotic-resistant pathogenic bacteria pose a high threat to human health, bacterial multidrug efflux pumps become major contributors to the high-level antibiotic resistance in most microorganisms. Since traditional antibiotics are still indispensable currently, we report a dual drug delivery system to maximize the antibacterial efficacy of antibiotics by inhibiting efflux pumps in bacteria before their exposure to antibiotics. In this research, a microsphere/hydrogel composite was constructed from ciprofloxacin (Cip)-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres and ginsenoside Rh2 (G-Rh2) dispersed thermo-sensitive hydrogel to treat skin infections. In vitro drug release studies indicated that while G-Rh2 in hydrogel presented a faster and short-term release manner to rapidly inhibit the NorA efflux pumps, Cip showed a sustained and long-term release behavior to provide a local high concentration gradient for facilitating drug percutaneous penetration. The combination of Cip and G-Rh2 demonstrated a high degree of synergism against both methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA), hence significantly improving their in vitro antibacterial activity and efficiency. Moreover, the antibacterial performance of the microsphere/hydrogel composite with a sequential release profile is superior to that of other formulations in mouse model of MRSA skin infections, indicating its great potential to treat antibiotic-resistant skin infections.
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高影响因子
Artificial Cells Nanomedicine and Biotechnology
·
2019
·
IF 4.462
Chenghua Liang,Nan Li,Zikai Cai,Rongpu Liang,Xiaoming Zheng,Li Deng,Longbao Feng,Rui Guo,Bo Wei
At present, cancer is the first cause of death for humans, but early detection and treatment can help improve prognoses and reduce mortality. However, further development of carrier-assistant drug delivery systems (DDSs) is retarded by the aspects such as the low drug-carrying capacity, carrier-induced toxicity and immunogenicity, complex synthesis manipulation. The development of nanoscale drug delivery systems (NDDS) have been rapidly developed to address these issues. In this article, we used PLGA-PEG with good biocompatibility to encapsulate Fe3O4 nanoparticles (a magnetic resonance imaging contrast agent) and DOX (an antitumour drug) via the emulsion-solvent evaporation method, aimed at achieving a dual function of the early detection and the treatment of mammary cancer. The results showed that the Fe3O4/DOX/PLGA-PEG nanoparticles had a relatively uniform size, a high carrier rate of Fe3O4 and high encapsulation efficiency of DOX, and a relatively high activity of released DOX within 120 h. In addition, in vitro studies showed that the Fe3O4/DOX/PLGA-PEG nanoparticles were cytocompatibility in NIH 3T3 fibroblast cells culture study while had a special effect on destroying human breast cancer MCF-7 cells compared with pure DOX solution. In vitro studies revealed that the Fe3O4/DOX/PLGA-PEG enabled enhanced T2 contrast magnetic resonance. Overall, our multifunctional Fe3O4/DOX/PLGA-PEG nanoparticles, composed of biocompatible substances and therapeutic/imaging materials, have great potential for the early detection of cancer and accurate drug delivery via the dynamic monitoring using MRI.
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高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Yuying Chen,Qingwei He,Huangjie Lu,Jie Yang,Jiongming Han,Ying Zhu,Ping Hu
This study addresses the challenging task of quantitatively investigating drug release from PLGA microspheres after in vivo administration. The objective is to employ Förster resonance energy transfer (FRET) to visualize drug-encapsulated microspheres in both in vitro and in vivo settings. The primary goal is to establish a quantitative correlation between FRET fluorescence changes and microsphere drug release. The study selects drugs with diverse structures and lipid solubility to explore release mechanisms, using PLGA as the matrix material. Clozapine and risperidone serve as model drugs. FRET molecules, Cy5 and Cy5.5, along with Cy7 derivatives, create FRET donor–acceptor pairs. In vitro results show that FRET fluorescence changes align closely with microsphere drug release, particularly for the Cy5.5-Cy7 pair. In vivo experiments involve subcutaneous administration of microspheres to rats, tracking FRET fluorescence changes while collecting blood samples. Pharmacokinetic studies on clozapine and risperidone reveal in vivo absorption fractions using the Loo-Riegelman method. Correlating FRET and in vivo absorption data establishes an in vitro – in vivo relationship (IVIVR). The study demonstrates that FRET-based fluorescence changes quantitatively link to microsphere drug release, offering an innovative method for visualizing and monitoring release in both in vitro and in vivo settings, potentially advancing clinical applications of such formulations.
研究领域:
药剂学
·
生物医学工程
·
药理学
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高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Xuemeng Guo,Xiang Li,Sijie Wang,Yingying Shi,Jiaxin Huang,Xu Liu,Yichao Lu,Junlei Zhang,Lihua Luo,Jian You
Adoptive cell therapy (ACT) emerged as a promising approach for cancer treatment, yet its application in solid tumors faced challenges such as inadequate tumor infiltration and cellular dysfunction. Histone acetylation is reported to play a crucial role in restoring T-cell function within tumor tissues. Building upon previous research, a novel strategy involving the co-loading of two drugs, G3C12 and vorinostat (SAHA), into PLGA microspheres to form G3C12+SAHA@PLGA is developed for intratumoral injection. The G3C12 peptide enhances adoptive T-cell recruitment to the tumor site by modulating the binding state of IFN-γ. While SAHA, a histone deacetylase inhibitor, promotes memory phenotypes of infiltrating T-cells and prevents their transition to an exhausted state. This synergistic approach effectively augmentes the efficacy of ACT in the “cold” tumor model (4T1) or the “hot” tumor model (CT26). These findings highlight the potential of combining epigenetic regulation with recruitment signaling as a means to enhance the therapeutic impact of ACT in treating solid tumors.
研究领域:
肿瘤免疫学
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表观遗传学
·
癌症治疗
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高影响因子
BIOMATERIALS
·
2015
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IF 8.557
Lei Zhang,Zhanzhuang Zeng,Chaohua Hu,Susan L. Bellis,Wendi Yang,Yintao Su,Xinyan Zhang,Yunkun Wu
Conventional oral vaccines with simple architecture face barriers with regard to stimulating effective immunity. Here we describe oral vaccines with an intelligent phase-transitional shielding layer, poly[(methyl methacrylate)-co-(methyl acrylate)-co-(methacrylic acid)]-poly( d , l -lactide-co-glycolide) (PMMMA-PLGA), which can protect antigens in the gastro-intestinal tract and achieve targeted vaccination in the large intestine. With the surface immunogenic protein (SIP) from group B Streptococcus (GBS) entrapped as the antigen, oral administration with PMMMA-PLGA (PTRBL)/Trx-SIP nanoparticles stimulated robust immunity in tilapia , an animal with a relatively simple immune system. The vaccine succeeded in protecting against Streptococcus agalactiae , a pathogen of worldwide importance that threatens human health and is transmitted in water with infected fish. After oral vaccination with PTRBL/Trx-SIP, tilapia produced enhanced levels of SIP specific antibodies and displayed durability of immune protection. 100% of the vaccinated tilapia were protected from GBS infection, whereas the control groups without vaccines or vaccinated with Trx-SIP only exhibited respective infection rates of 100% or >60% within the initial 5 months after primary vaccination. Experiments in vivo demonstrated that the recombinant antigen Trx-SIP labeled with FITC was localized in colon, spleen and kidney, which are critical sites for mounting an immune response. Our results revealed that, rather than the size of the nanoparticles, it is more likely that the negative charge repulsion produced by ionization of the carboxyl groups in PMMMA shielded the nanoparticles from uptake by small intestinal epithelial cells. This system resolves challenges arising from gastrointestinal damage to antigens, and more importantly, offers a new approach applicable for oral vaccination.
研究领域:
疫苗学
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免疫学
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水产养殖
·
微生物学
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高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Qiaoyu Liu,Juanjuan Chai,Xinrui Zhang,Jingwen Xue,Lu Qin,Jian Guan,Xin Zhang,Bingjie Ma,Shirui Mao
Inhalable nanomedicines hold great promise for lung cancer therapy, yet how carrier structure dictates their pulmonary fate remains insufficiently understood. From a fundamental research perspective, this study aims to investigate how structurally distinct nanocarriers interact with physiopathological barriers in the lungs, with the goal of providing a theoretical foundation for inhalation therapy. By keeping the composition and material properties of the carriers comparable, different structured paclitaxel-loaded mPEG-PLGA nanocarriers, including nanoparticles, polymersomes, and micelles, were prepared by selecting different hydrophobic chain mPEG-PLGA diblock copolymers. It was found that nanoparticles with solid structure showed the slowest drug release rate, and the strongest cellular uptake but are difficult to overcome the barriers in the lung mucus with limited tumor permeability. In contrast, polymersomes with a less rigid structure have a better capacity to overcome the mucus and tumor barrier and therefore have the best lung retention but the weakest cellular uptake. The micelles with the smallest particle size have the strongest tumor permeability and the most prominent lymphatic distribution but the fastest drug release rate thus the most prominent extrapulmonary distribution. Remarkably, despite these divergent behaviors, their overall antitumor efficacy converged, revealing a compensatory balance among structural advantages and limitations. By bridging mechanistic insights with therapeutic outcomes, this study establishes a structure–function framework for pulmonary delivery. These findings advance fundamental understanding of how nanocarrier structure shapes drug fate and efficacy and provide generalizable principles to guide the rational design and clinical translation of inhalable nanomedicines for lung cancer and other pulmonary diseases.
研究领域:
纳米医学
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药物递送系统
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肺部药理学
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癌症治疗
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生物材料
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纳米技术
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PubMed
高影响因子
MICROBIAL PATHOGENESIS
·
2021
·
IF 3.738
Xiufen Du,Daquan Tan,Yang Gong,Yifan Zhang,Jiangyuan Han,Wei Lv,Tao Xie,Pu He,Zongjie Hou,Kun Xu,Jiying Tan,Bingdong Zhu
Protein-based subunit vaccine against tuberculosis (TB) is regarded as safer but with lower immunogenicity . To investigate effective adjuvant to improve the immunogenicity of TB subunit vaccine, we modified ploy(I:C) onto PLGA-PEG copolymer nanoparticle with polydopamine to produce a new nanoparticle adjuvant named “PLGA-PEG-poly(I:C)” (NP). M. tuberculosis fusion proteins Mtb10.4-HspX and ESAT-6-Rv2626c (M4) were encapsulated in the nanoparticles to produce the NP/M4 subunit vaccine. The PLGA-PEG/M4 nanoparticle was 200.21 ± 1.07 nm in diameter, and the polydispersity index (PDI) was 0.127 ± 0.02. Following modification with poly(I:C) by polydopamine, the NP/M4 was administered to C57BL/6 female mice intranasally and the immune responses were evaluated. The NP/M4 significantly induced antigen-specific CD4 + T cells proliferation, IL-2 and IFN-γ production. In addition, the NP/M4 could promote the production of antigen-specific IgG, IgG1 , IgG2c in serum, and sIgA in lung washings . Overall, our results indicated that the NP would be a potential TB subunit vaccine adjuvant with the ability to induce strong Th1-type cell-mediated immunity and humoral immune responses .
研究领域:
免疫学
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疫苗学
·
纳米技术
·
结核病
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PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2021
·Vol. 17
·期 6
·1007-1019
·
IF 4.099
Cui Miao,Zhang Hui-Ru,Ouyang Fan,Guo Yu-Qi,Li Rui-Fang,Duan Shao-Feng,Xiong Tian-Di,Wang Yun-Long,Wang Xue-Qin
In recent years, the emergence of non-toxic but catalytically active inorganic nanoparticles has attracted great attention for cancer treatment, but the therapeutic effect has been affected by the limited reactive oxygen species in tumors. Therefore, the combination of chemotherapy
and chemodynamic therapy is regarded as a promising therapeutic strategy. In this paper, we reported the preparation and bioactivity evaluation of poly(lactic acid-co-glycolic acid) (PLGA) grafted-γ-Fe2O3 nanoparticles with dual response of endogenous
peroxidase and catalase like activities. Our hypothesis is that PLGAgrafted γ-Fe2O3 nanoparticles could be used as a drug delivery system for the anti-tumor drug doxorubicin to inhibit the growth of lung adenocarcinoma A549 cells; meanwhile, based on its
mimic enzyme properties, this kind of nanoparticles could be combined with doxorubicin in the treatment of A549 cells. Our experimental results showed that the PLGAgrafted γ-Fe2O3 nanoparticles could simulate the activity of catalase and decompose hydrogen
peroxide into H2O and oxygen in neutral tumor microenvironment, thus reducing the oxidative damage caused by hydrogenperoxide to lung adenocarcinoma A549 cells. In acidic microenvironment, PLGA grafted γ-Fe2O3 nanoparticles could simulate the activity
of peroxidase and effectively catalyze the decomposition of hydrogen peroxide to generate highly toxic hydroxyl radicals, which could cause the death of A549 cells. Furthermore, the synergistic effect of peroxidase-like activity of PLGA-grafted γ-Fe2O3 nanoparticles
and doxorubicin could accelerate the apoptosisand destruction of A549 cells, thus enhancing the antitumor effect of doxorubicin-loaded PLGA-grafted γ-Fe2O3 nanoparticles. Therefore, this study provides an effective nanoplatform based on dual inorganic biomimetic
nanozymes for the treatment of lung cancer.
研究领域:
纳米技术
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癌症治疗
·
材料科学
·
生物化学
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PubMed
高影响因子
APPLIED SURFACE SCIENCE
·
2025
·
IF 6.9
Yuemei Li,Yongmei Li,Yunfei Qu
Zn alloy stents, as implantable cardiac devices, have broad application prospects in the field of heart. However, excessive Zn 2+ release during degradation remains a challenge for biocompatibility. Here, the Yb/Er/CeO 2 coating is grown on the Zn substrate, which inhibits the release of Zn 2+ and enhances the corrosion resistance of Zn stent. Under 980 nm excitation, the Yb/Er/CeO 2 coating enables electron transitions from the valence band to the conduction band. This process catalyzes H 2 O and O 2 to generate reactive oxygen species (ROS), such as ∙OH. These ROS act as chemical linkers to accelerate the deposition of the drug-eluting PLGA coating. The Zn@Yb/Er/CeO 2 /PLGA composite demonstrates excellent biodegradability. It shows great potential for treating cardiovascular diseases.
研究领域:
材料科学
·
生物医学工程
·
心血管医学
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高影响因子
危险品化学品经营许可证（带存储）