INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Yiduo Liu,Meizhen Long,Yuanzhi Wang,Zhengmin Liang,Yuhui Dong,Mengjin Qu,Xin Ge,Yue Nan,Yulan Chen,Xiangmei Zhou
Vaccination is the most effective method for preventing infectious diseases. Oral vaccinations have attracted much attention due to the ability to boost intestinal and systemic immunity. The focus of this study was to develop a poly (lactide- co -glycolide) acid (PLGA)-based ternary polyelectrolyte complex (PEC) with chitosan, sodium alginate, and transmembrane peptides R8 for the delivery of antigen proteins. In this study, the antigen protein (HBf), consisting of the Mycobacterium avium subspecies paratuberculosis (MAP) antigens HBHA, Ag85B, and Bfra, was combined with R8 to generate self-assembled conjugates. The results showed that PEC presented a cross-linked reticular structure to protect the encapsulated proteins in the simulated gastric fluid. Then, the nanocomposite separated into individual nanoparticles after entering the simulated intestinal fluid. The ternary PEC with R8 promoted the in vivo uptake of antigens by intestinal lymphoid tissue. Moreover, the ternary PEC administered orally to mice promoted the secretion of specific antibodies and intestinal mucosal IgA. In addition, in the mouse models of MAP infection, the ternary PEC enhanced splenic T cell responses, thus reducing bacterial load and liver pathology score. These results suggested that this ternary electrolyte complex could be a promising delivery platform for oral subunit vaccine candidates, not limited to MAP infection.
研究领域:
疫苗学
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免疫学
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药学
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微生物学
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生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2025
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IF 4.9
Xueling Long,Siyi Li,Yuxiang Ma,Yuting Cao,Shaoping Sun
Transdermal delivery is considered as a promising convenient and painless approach for the delivery of insulin. In this study, an amphiphilic peptide derivative of oleic acid modified octaarginine (R8-OA) and a photothermal nanomaterial of hyaluronic acid modified CuS (CuS-HA) were successfully synthesized. Using both materials as carriers, CuS-HA enveloped R8-OA@insulin nanocomplexes (HERNCs) were prepared. In vitro studies demonstrated that R8-OA could chemically enhance the penetration of insulin through the stratum corneum. In vivo laser activation studies suggested that CuS-HA in HERNCs could ablate the stratum corneum, thus facilitating the insulin penetration through physical enhancement. The hypoglycemic effect study revealed that blood glucose level in diabetic mice decreased to 42.3% within 4 h, and the value was maintained at 75.1% after 24 h. These results underscored the potential of the enveloped nanocomplexes for enhanced transdermal delivery of insulin.
研究领域:
纳米医学
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药物递送
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透皮治疗
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糖尿病治疗
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生物材料
✓ 已验证
产品关联
DOI
高影响因子
MICROPOROUS AND MESOPOROUS MATERIALS
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2021
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IF 5.455
Qunqun Du,Qiang Liu
Excessive UV irradiation induces photoaging and overproduction of melanin , which darkens the skin and affects appearance. To efficiently enhance transdermal delivery and anti-pigmentation, a novel ROS-responsive transdermal nanocarrier for the whitening agent Glabridin by integrating the cell-penetrating peptide polyarginine R8 and borate ester bond into hollow mesoporous silica nanoparticles (HMSNs) has been designed, in which beta-cyclodextrin (β-CD) was grafted onto the surfaces of HMSNs via boronic ester bond to avoid premature release of Glabridin, and R8 conjugated adamantane (Ada) was anchored on HMSN-β-CD via host-gust interaction to enhance the drug delivery efficiency. The ROS-responsive HMSN-β-CD/Ada-R8 nanocarrier was characterized by TEM, FTIR , TGA , Zeta potential , N 2 adsorption, stability, and other parameters. The nanocarrier rapidly penetrated through the epidermis into the keratinocytes and melanocytes and released Glabridin in a controlled ROS-responsive manner. Glabridin released from nanocarriers reversed UV-induced oxidative damage and phototoxicity and reduced hyperpigmentation. Taken together, our study provides a guidance for the design and fabrication of functional transdermal drug nanocarriers for cosmetic applications.
研究领域:
化妆品科学
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纳米技术
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药学
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材料科学
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皮肤科
✓ 已验证
DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2024
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IF 6.9
Sikai Deng,Weiwei Li,Qiyu Chen,Jianqun Shao,Junbo Zhang,Yuji Wang,Yinghuan Li
The mucus layer and intestine epithelium pose challenges to the bioavailability of orally administered paclitaxel (PTX). A novel P-glycoprotein inhibitor, (S)-2-decanoylamino-3-(1-naphthyl)propionyl-leucyl-valine (PgpI), was synthesized in this study. Its structure was characterized using 1 H NMR, 13 C NMR, ESI-MS and IR spectroscopies. The efficacy and in vivo toxicity of PgpI were comprehensively evaluated by R8-PEG@PLs&PgpI, i.e. , the oral combination of PgpI and octaarginine R8-PEG-DSPE modified PTX liposomes (R8-PEG@PLs), for lung cancer treatment. The joint forms between PgpI and R8-PEG@PLs were investigated and the affinity of PgpI for intestinal P-glycoprotein remained unaffected when combined externally with R8-PEG@PLs (R8-PEG@PLs&PgpI), compared to the diminished affinity for internal combination. The primary endocytic pathway for R8-PEG@PLs&PgpI in Caco-2 cells was the lipid raft, with increased percentage of macropinocytosis compared to unmodified PTX liposomes (PLs). The established physiology-based cellular kinetic models revealed that the net internalization rate of PTX was 2.3 times higher in R8-PEG@PLs&PgpI than in PLs, correlating with in vivo 2.2 times of antitumor rate. R8-PEG@PLs&PgpI may address the deficits of PLs in human lung A549 tumor-bearing mice due to the lower drug concentration than in normal mice. The external combination of R8-PEG@PLs&PgpI, offering maximal efficacy and security of PgpI, is promising for oral PTX delivery.
研究领域:
药学
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肿瘤学
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药物递送系统
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2022
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IF 6.51
Yan Liang,Ping-Yu Wang,You-Jie Li,Ze-Yun Liu,Ran-Ran Wang,Guang-Bin Sun,Hong-Fang Sun,Shu-Yang Xie
Reduced drug uptake and elevated drug efflux are two major mechanisms in cancer multidrug resistance (MDR). In the present study, a new multistage O 2 -producing liposome with NAG/R8-dual-ligand and stimuli-responsive dePEGylation was developed to address the abovementioned issues simultaneously. The designed C-NAG-R8-PTXL/MnO 2 -lip could also achieve magnetic resonance imaging (MRI)-guided synergistic chemodynamic/chemotherapy (CDT/CT). In vitro and in vivo studies showed that C-NAG-R8-PTXL/MnO 2 -lip enhanced circulation time by PEG and targeted the tumor site. After tumor accumulation, endogenous l -cysteine was administered, and the PEG-attached disulfide bond was broken, resulting in the dissociation of PEG shells. The previously hidden positively charged R8 by different lengths of PEG chains was exposed and mediated efficient internalization. In addition, the oxygen (O 2 ) generated by C-NAG-R8-PTXL/MnO 2 -lip relieved the hypoxic environment within the tumor, thus reducing the efflux of chemotherapeutic drug. O 2 was able to burst liposomes and triggered the release of PTXL . The toxic hydroxyl radical (·OH), which was produced by H 2 O 2 and Mn 2+ , strengthened CDT/CT. C-NAG-R8-PTXL/MnO 2 -lip was also used as MRI contrast agent , which blazed the trail to rationally design theranostic agents for tumor imaging.
研究领域:
药学
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生物医学工程
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癌症研究
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纳米技术
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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