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β-catenin mRNA encapsulated in SM-102 lipid nanoparticles enhances bone formation in a murine tibia fracture repair model
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作者 Anna Laura Nelson Chiara Mancino +10 位作者 Xueqin Gao Joshua AChoe Laura Chubb Katherine Williams Molly Czachor Ralph Marcucio Francesca Taraballi John P.Cooke Johnny Huard Chelsea Bahney Nicole Ehrhart 《Bioactive Materials》 SCIE CSCD 2024年第9期273-286,共14页
Fractures continue to be a global economic burden as there are currently no osteoanabolic drugs approved to accelerate fracture healing.In this study,we aimed to develop an osteoanabolic therapy which activates the W... Fractures continue to be a global economic burden as there are currently no osteoanabolic drugs approved to accelerate fracture healing.In this study,we aimed to develop an osteoanabolic therapy which activates the Wnt/β-catenin pathway,a molecular driver of endochondral ossification.We hypothesize that using an mRNAbased therapeutic encodingβ-catenin could promote cartilage to bone transformation formation by activating the canonical Wnt signaling pathway in chondrocytes.To optimize a delivery platform built on recent advancements in liposomal technologies,two FDA-approved ionizable phospholipids,DLin-MC3-DMA(MC3)and SM-102,were used to fabricate unique ionizable lipid nanoparticle(LNP)formulations and then tested for transfection efficacy both in vitro and in a murine tibia fracture model.Using firefly luciferase mRNA as a reporter gene to track and quantify transfection,SM-102 LNPs showed enhanced transfection efficacy in vitro and prolonged transfection,minimal fracture interference and no localized inflammatory response in vivo over MC3 LNPs.The generatedβ-cateninGOF mRNA encapsulated in SM-102 LNPs(SM-102-β-cateninGOF mRNA)showed bioactivity in vitro through upregulation of downstream canonical Wnt genes,axin2 and runx2.When testing SM-102-β-cateninGOF mRNA therapeutic in a murine tibia fracture model,histomorphometric analysis showed increased bone and decreased cartilage composition with the 45μg concentration at 2 weeks post-fracture.μCT testing confirmed that SM-102-β-cateninGOF mRNA promoted bone formation in vivo,revealing significantly more bone volume over total volume in the 45μg group.Thus,we generated a novel mRNA-based therapeutic encoding aβ-catenin mRNA and optimized an SM-102-based LNP to maximize transfection efficacy with a localized delivery. 展开更多
关键词 Gene therapy Fracture healing lipid nanoparticles MRNA Canonical Wnt
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Functionalized lipid nanoparticles modulate the blood-brain barrier and eliminate α-synuclein to repair dopamine neurons
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作者 Xiaomei Wu Renxiang Yuan +4 位作者 Yichong Xu Kai Wang Hong Yuan Tingting Meng Fuqiang Hu 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2024年第2期120-135,共16页
The challenge in the clinical treatment of Parkinson's disease lies in the lack of disease-modifying therapies that can halt or slow down the progression. Peptide drugs, such as exenatide (Exe), with potential dis... The challenge in the clinical treatment of Parkinson's disease lies in the lack of disease-modifying therapies that can halt or slow down the progression. Peptide drugs, such as exenatide (Exe), with potential disease-modifying efficacy, have difficulty in crossing the blood-brain barrier (BBB) due to their large molecular weight. Herein, we fabricate multi-functionalized lipid nanoparticles (LNP) Lpc-BoSA/CSO with BBB targeting, permeability-increasing and responsive release functions. Borneol is chemically bonded with stearic acid and, as one of the components of Lpc-BoSA/CSO, is used to increase BBB permeability. Immunofluorescence results of brain tissue of 15-month-old C57BL/6 mice show that Lpc-BoSA/CSO disperses across the BBB into brain parenchyma, and the amount is 4.21 times greater than that of conventional LNP. Motor symptoms of mice in Lpc-BoSA/CSO-Exe group are significantly improved, and the content of dopamine is 1.85 times (substantia nigra compacta) and 1.49 times (striatum) that of PD mice. α-Synuclein expression and Lewy bodies deposition are reduced to 51.85% and 44.72% of PD mice, respectively. Immunohistochemical mechanism studies show AKT expression in Lpc-BoSA/CSO-Exe is 4.23 times that of PD mice and GSK-3β expression is reduced to 18.41%. Lpc-BoSA/CSO-Exe could reduce the production of α-synuclein and Lewy bodies through AKT/GSK-3β pathway, and effectively prevent the progressive deterioration of Parkinson's disease. In summary, Lpc-BoSA/CSO-Exe increases the entry of exenatide into brain and promotes its clinical application for Parkinson's disease therapy. 展开更多
关键词 Blood-brain barrier lipid nanoparticles Brain delivery facilitation α-Symuclein Parkinson's disease
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Acyclovir-Loaded Solid Lipid Nanoparticles: A Permeation and Penetrability Study
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作者 Anyoli Taly Adriana Camino +3 位作者 Cirana Rodriguez Evelyn Pena Alfredo Inatti Xenon Serrano 《Journal of Biosciences and Medicines》 2024年第10期316-327,共12页
Herpes simplex virus type I is a cutaneous infection treated with acyclovir. The topical treatment has therapeutic challenges due to the deficient delivery of the drug through epithelial barriers. This results in an i... Herpes simplex virus type I is a cutaneous infection treated with acyclovir. The topical treatment has therapeutic challenges due to the deficient delivery of the drug through epithelial barriers. This results in an inadequate drug-virus interaction in the basal epidermis (virus replication site). For this reason, it is essential to generate drug carrier systems that overcome these limitations. In this study, we evaluated the permeation (through in vitro test Franz cells) and penetration (by ex vivo test Tape Stripping) of a topical formulation of acyclovir loaded in solid lipid nanoparticles and a conventional formulation (Aciclor®). The acyclovir solid lipid nanoparticles were prepared using hot homogenization and sonication methods. The results yielded a particle size of 85 ± 2 nm, a polydispersity index of 0.24 ± 0.01, a zeta potential of −16 ± 2 mV, and 94% ± 3% of encapsulated drug. The in vitro test revealed that the permeability of acyclovir solid lipid nanoparticles formulation was superior compared to reference formulation, with values of 1473.74 ± 30.14 µg/cm2 for the solid lipid nanoparticles and 893.36 ± 38.09 µg/cm2 for the reference formulation. The ex vivo test demonstrated that acyclovir solid lipid nanoparticles exhibited superior penetrability through the stratum corneum compared to the reference formulation, with total amounts of 3767 µg for the solid lipid nanoparticles and 2162 µg for the reference formulation. These findings seem promising in advancing new effective therapies against herpes generated by herpes simplex virus type I. 展开更多
关键词 HERPES ACYCLOVIR Solid lipid nanoparticles Franz Cells Tape Stripping
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Monitoring the in vivo siRNA release from lipid nanoparticles based on the fluorescence resonance energy transfer principle 被引量:1
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作者 Lei Sun Jinfang Zhang +11 位作者 Jing-e Zhou JingWang Zhehao Wang Shenggen Luo Yeying Wang Shulei Zhu Fan Yang Jie Tang Wei Lu Yiting Wang Lei Yu Zhiqiang Yan 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2023年第1期72-85,共14页
The siRNA-loaded lipid nanoparticles have attracted much attention due to its significant gene silencing effect and successful marketization.However,the in vivo distribution and release of siRNA still cannot be effect... The siRNA-loaded lipid nanoparticles have attracted much attention due to its significant gene silencing effect and successful marketization.However,the in vivo distribution and release of siRNA still cannot be effectively monitored.In this study,based on the fluorescence resonance energy transfer(FRET)principle,a fluorescence dye Cy5-modified survivin siRNA was conjugated to nanogolds(Au-DR-siRNA),which were then wrapped with lipid nanoparticles(LNPs)for monitoring the release behaviour of siRNA in vivo.The results showed that once Au-DR-siRNA was released from the LNPs and cleaved by the Dicer enzyme to produce free siRNA in cells,the fluorescence of Cy5 would change from quenched state to activated state,showing the location and time of siRNA release.Besides,the LNPs showed a significant antitumor effect by silencing the survivin gene and a CT imaging function superior to iohexol by nanogolds.Therefore,this work provided not only an effective method for monitoring the pharmacokinetic behaviour of LNP-based siRNA,but also a siRNA delivery system for treating and diagnosing tumors. 展开更多
关键词 Survivin siRNA lipid nanoparticles In vivo release Nanogolds Fluorescence resonance energy transfer
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Characteristics and Transdermal Drug Delivery of Triamcinolone-Acetonide-Acetate-Loaded Solid Lipid Nanoparticles Carbomer Gel 被引量:3
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作者 刘卫 朱姚亮 +1 位作者 陈华兵 杨祥良 《Journal of Chinese Pharmaceutical Sciences》 CAS 2005年第1期18-24,共7页
Aim To prepare triamcinolone-acetonide-acetate (TAA)-loaded solid lipidnanoparticles (SLN) carbomer gel with tripalmitin glyceride (TPG), and investigate theircharacteristics and transdermal drug delivery. Methods SLN... Aim To prepare triamcinolone-acetonide-acetate (TAA)-loaded solid lipidnanoparticles (SLN) carbomer gel with tripalmitin glyceride (TPG), and investigate theircharacteristics and transdermal drug delivery. Methods SLN suspension was prepared by high-pressurehomogenization technique, and then mixed with carbomer gel matrix to get SLN gel. The morphology,particle size with polydispersi-ty index (PI) and zeta potential were examined by atomic forcemicroscopy (AFM) and photon correlation spectroscopy (PCS). The entrapment efficiency, stability andin vitro drug release were also studied. The transdermal drug delivery through porcine ear skin wasevaluated using modified Franz diffusion cells. Results The SLN had a spherical shape with theaverage size of (95.5 - 186.2) nm, the zeta potential of (-26.3- -15.7) mV and the entrapmentefficiency of 67.4%-90.3% for different TAA encapsulated compounds. TAA-SLN carbomer gel had goodstability, the release profile in vitro fitted Higuchi equation. In comparison with conventionalhydrogels, TAA-SLN carbomer gel resulted in higher drug permeation amount and drug deposition withinporcine ear skin after 24 h penetration experiment. Conclusion TAA-SLN carbomer gel is preparedwith stable physicochemical properties. The release profile and improved drug permeation into skinmake it be a promising vehicle for transdermal drug delivery. 展开更多
关键词 solid lipid nanoparticles carbomer gel triarnconolone-acetonide-acetate characterization transdermal drug delivery
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Targeting the resolution pathway of inflammation using Ac2–26 peptide-loaded PEGylated lipid nanoparticles for the remission of rheumatoid arthritis 被引量:5
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作者 Xianyan Qin Liming He +3 位作者 Donghao Fan Wenlang Liang Qin Wang Jiyu Fang 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2021年第4期483-493,共11页
Rheumatoid arthritis(RA)is a common autoimmune disease characterized by joint inflammation and immune dysfunction.Although various therapeutic approaches have been utilized for the treatment of RA in clinical applicat... Rheumatoid arthritis(RA)is a common autoimmune disease characterized by joint inflammation and immune dysfunction.Although various therapeutic approaches have been utilized for the treatment of RA in clinical applications,the low responsiveness of RA patients and undesired systemic toxicity are still unresolved problems.Targeting the resolution pathway of inflammation with pro-resolving mediators would evoke the protective actions of patient for combating the inflammation.Ac2–26,a 25-amino acid peptide derived from Annexin A(a pro-resolving mediator),has shown good efficacy in the treatment of inflammatory disorders.However,the low bioavailability of Ac2–26 peptides hinders their efficacy in vivo.In this paper,we formed PEGylated lipid nanoparticles(LDNPs)by the co-assembly of l-ascorbyl palmitate(L-AP)and N-(carbonyl methoxypolyethylene glycol-2000)-1,2-distearoyl-sn–glycero-3-phosphoethanolamine(DSPE-PEG 2 k)to encapsulate and deliver Ac2–26 peptides to the arthritic rats.They showed good stability and biocompatibility.After being intravenously administrated,Ac2–26 peptide-loaded PEGylated lipid nanoparticles(ADNPs)showed the prolonged in vivo circulation time and enhanced accumulation in inflamed sites.In vivo therapeutic evaluations revealed that ADNPs could attenuate synovial inflammation and improve joint pathology.Therefore,the pro-resolving therapeutic strategy using ADNPs is effective in RA treatment. 展开更多
关键词 Pegylated lipid nanoparticles Drug delivery Pro-resolving therapy Ac2–26 peptide Rheumatoid arthritis
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Homogeneous PLGA-lipid nanoparticle as a promising oral vaccine delivery system for ovalbumin 被引量:4
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作者 Tongtong Ma Lianyan Wang +2 位作者 Tingyuan Yang Guanghui Ma Siling Wang 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2014年第3期129-136,共8页
In this study,a polymeric lipid nanoparticle(NP)(simplified as Lipid NP)was reported as a promising oral vaccine delivery system.The Lipid NPs composed of a hydrophobic polymeric poly(D,L-lactide-co-glycolide)(PLGA)co... In this study,a polymeric lipid nanoparticle(NP)(simplified as Lipid NP)was reported as a promising oral vaccine delivery system.The Lipid NPs composed of a hydrophobic polymeric poly(D,L-lactide-co-glycolide)(PLGA)core and a surface coating of lipid monolayer.Membrane emulsification technique was used to obtain uniform-sized Lipid NPs.Ovalbumin(OVA)was used as a model vaccine.Compared with the pure PLGA NPs,the Lipid NPs achieved higher loading capacity(LC)and entrapment efficiency(EE)for the encapsulated OVA.An in vitro oral release profile showed that the OVA-Lipid NPs were with lower initial burst and could protect the loaded OVA from the harsh gastrointestinal(GI)environment for a long time.In addition,a human microfold cell(M-cell)transcytotic assay demonstrated that due to a lipid layer structure on the particle surface,the Lipid NPs showed higher affinity to the M-cells.Since the M-cell in the intestinal epithelium played an important role in particle transportation as well as intimately associated with the underlying immune cells,the OVA-Lipid NPs effectively induced mucosal and humoral immune responses. 展开更多
关键词 Oral delivery VACCINE Polymeric lipid nanoparticle M-cell affinity
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Lipid nanoparticle-mediated CRISPR/Cas9 gene editing and metabolic engineering for anticancer immunotherapy 被引量:3
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作者 Hyemin Ju Dongyoon Kim Yu-Kyoung Oh 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2022年第5期641-652,共12页
Metabolic engineering of the tumor microenvironment has emerged as a new strategy.Lactate dehydrogenase A(LDHA)is a prominent target for metabolic engineering.Here,we designed a cationic lipid nanoparticle formulation... Metabolic engineering of the tumor microenvironment has emerged as a new strategy.Lactate dehydrogenase A(LDHA)is a prominent target for metabolic engineering.Here,we designed a cationic lipid nanoparticle formulation for LDHA gene editing.The plasmid DNA delivery efficiency of our lipid nanoparticle formulations was screened by testing the fluorescence of lipid nanoparticles complexed to plasmid DNA encoding green fluorescence protein(GFP).The delivery efficiency was affected by the ratios of three components:a cationic lipid,cholesterol or its derivative,and a fusogenic lipid.The lipid nanoparticle designated formulation F3 was complexed to plasmid DNA co-encoding CRISPR-associated protein 9 and LDHA-specific sgRNA,yielding the lipoplex,pCas9-sgLDHA/F3.The lipoplex including GFP-encoding plasmid DNA provided gene editing in HeLa-GFP cells.Treatment of B16F10 tumor cells with pCas9-sgLDHA/F3 yielded editing of the LDHA gene and increased the pH of the culture medium.pCas9-sgLDHA/F3 treatment activated the interferon-gamma and granzyme production of T cells in culture.In vivo,combining pCas9-sgLDHA/F3 with immune checkpoint-inhibiting anti-PD-L1 antibody provided a synergistic antitumor effect and prolonged the survival of tumor model mice.This study suggests that combining metabolic engineering of the tumor microenvironment with immune checkpoint inhibition could be a valuable antitumor strategy. 展开更多
关键词 Gene editing lipid nanoparticle Metabolic engineering Lactate dehydrogenase A Tumor microenvironment
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New research on development of solid lipid nanoparticles 被引量:2
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作者 侯君 周世文 《Journal of Medical Colleges of PLA(China)》 CAS 2007年第6期385-390,共6页
To review the latest research development of the solid lipid nanoparticles(SLN) according to the recent relevant literatures.Each preparations of the SLN have advantages and disadvantages.Among the total preparations ... To review the latest research development of the solid lipid nanoparticles(SLN) according to the recent relevant literatures.Each preparations of the SLN have advantages and disadvantages.Among the total preparations of the SLN.the high pressure homogenization(HPH) and the microemulsion tech- nique are to praise highly.The drug incorporation and release profiles could be modified as adjustment of production parameters.The SLNis an excellent drug delivery system and has broad prospects in the phar- maceutical field. 展开更多
关键词 solid lipid nanoparticles preparation technique drug administration solid lipid nanoparticles
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Efficacy of combined albendazol and praziquntel and their loaded solid lipid nanoparticles components in chemoprophylaxis of experimental hydatidosis 被引量:1
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作者 Ali Jelowdar Abdollah Rafiei +2 位作者 Mohammad Reza Abbaspour Iran Rashidi Mahmood Rahdar 《Asian Pacific Journal of Tropical Biomedicine》 SCIE CAS 2017年第6期549-554,共6页
Objective:To evaluate the efficacy of combined ABZ and PZQ and their solid lipid nanoparticles in chemoprophylaxis of cystic echinococcosis(CE).Methods:ABZ and PZQ loaded solid lipid nanoparticles(SLNs) were prepared ... Objective:To evaluate the efficacy of combined ABZ and PZQ and their solid lipid nanoparticles in chemoprophylaxis of cystic echinococcosis(CE).Methods:ABZ and PZQ loaded solid lipid nanoparticles(SLNs) were prepared by high shear homogenization and microemulsion congealing techniques with some minor modification.Nanoparticles average size,polydispersity index(PDI),and particle size distribution were determined by scanning electron microscopy(SEM) and photon correlation spectroscopy.Forty females BALB/c were experimentally infected by protoscoleces(PSC) and randomly divided into four equal groups of 10 mice.After the end of the 3 months treatment period and 2 months rest,mice were sacrificed and the peritoneal cavity was opened for removal,counting,measuring,and histological analysis of hydatid cyst.Results:The results indicated that ABZ and PZQ chemoprophylaxis treatment reduced the wet weight and size of developed cysts 77.3% and 79%,respectively.The corresponding result for the ABZ and PZQ loaded SLNs was 83% and 85%,respectively.Conclusions:This study for the first time demonstrated that ABZ and PZQ loaded SLNs is superior to free ABZ and PZQ for the chemoprophylaxis of CE in mice. 展开更多
关键词 ECHINOCOCCOSIS ALBENDAZOLE PRAZIQUANTEL High pressure homogenization Solid lipid nanoparticles(SLNs)
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Synthetic and nature-derived lipid nanoparticles for neural regeneration 被引量:1
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作者 Yuji S.Takeda Qiaobing Xu 《Neural Regeneration Research》 SCIE CAS CSCD 2015年第5期689-690,共2页
Challenges and opportunities in nerve regeneration: The central nervous system (CNS) has a limited ability to regen- erate. Subsequent to spinal injury, glial scar formation, creat- ed by fibroblasts, neuroglia, mo... Challenges and opportunities in nerve regeneration: The central nervous system (CNS) has a limited ability to regen- erate. Subsequent to spinal injury, glial scar formation, creat- ed by fibroblasts, neuroglia, monocytes, and endothelial cells, inhibits regeneration of the injured nerve. The peripheral nervous system (PNS) has a greater regeneration potential than the CNS; however, the current gold standard of treat- ment for a large nerve defect is still autologous nerve grafts, which require multiple surgeries. For this reason, researchers have been trying to regenerate nervous tissues, including brain, spinal cord. and PeriPheral nerves, for decades. 展开更多
关键词 Synthetic and nature-derived lipid nanoparticles for neural regeneration RVG RNA GENE NGF
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Preparation, optimization, and characterization of chitosancoated solid lipid nanoparticles for ocular drug delivery 被引量:1
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作者 Fengzhen Wang Mingwan Zhang +5 位作者 Dongsheng Zhang Yuan Huang Li Chen Sunmin Jiang Kun Shi Rui Li 《The Journal of Biomedical Research》 CAS CSCD 2018年第6期411-423,共13页
The present study aimed to develop and optimize chitosan coated solid lipid nanoparticles(chitosan-SLNs)encapsulated with methazolamide. Chitosan-SLNs were successfully prepared by a modified oil-in-water emulsificati... The present study aimed to develop and optimize chitosan coated solid lipid nanoparticles(chitosan-SLNs)encapsulated with methazolamide. Chitosan-SLNs were successfully prepared by a modified oil-in-water emulsification-solvent evaporation method with glyceryl monostearate as the solid lipid and phospholipid as the surfactant. Systematic screening of formulation factors was carried out. The optimized formula for preparation was screened by orthogonal design as well as Box-Behnken design with entrapment efficiency, particle size and zeta potential as the indexes. The entrapment efficiency of the optimized formulation(methazolamide-chitosan-SLNs)prepared was(58.5± 4.5)%,Particle size(247.7 ± 17.3) nm and zeta potential(33.5 ±3.9) mV. Transmission electron microscopy showed homogeneous spherical particles in the nanometer range. A prolonged methazolamide in vitro release profile was obtained in the optimized chitosan-SLNs suspension compared with methazolamide solution. No ocular damages were observed in the susceptibility test on albino rabbits. The results suggest that the combination of orthogonal design and Box-Behnken design is efficient and reliable in the optimization of nanocarriers, and chitosanSLNs is a potential carrier for ophthalmic administration. 展开更多
关键词 solid lipid nanoparticle orthogonal design Box-Behnken design ophthalmic administration CHITOSAN
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Solid lipid nanoparticles loading adefovir dipivoxil for antiviral therapy 被引量:1
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作者 Min-wei LI Jing MIAO +2 位作者 Sai-ping JIANG Fu-qiang HU Yong-zhong DU 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2008年第6期506-510,共5页
Herein,solid lipid nanoparticles(SLN)were proposed as a new drug delivery system for adefovir dipivoxil(ADV). The octadecylamine-fluorescein isothiocynate(ODA-FITC)was synthesized and used as a fluorescence maker to b... Herein,solid lipid nanoparticles(SLN)were proposed as a new drug delivery system for adefovir dipivoxil(ADV). The octadecylamine-fluorescein isothiocynate(ODA-FITC)was synthesized and used as a fluorescence maker to be incorporated into SLN to investigate the time-dependent cellular uptake of SLN by HepG2.2.15.The SLN of monostearin with ODA-FITC or ADV were prepared by solvent diffusion method in an aqueous system.About 15 wt%drug entrapment efficiency(EE)and 3 wt% drug loading(DL)could be reached in SLN loading ADV.Comparing with free ADV,the inhibitory effects of ADV loaded in SLN on hepatitis B surface antigen(HBsAg),hepatitis B e antigen(HBeAg)and hepatitis B virus(HBV)DNA levels in vitro were significantly enhanced. 展开更多
关键词 Adefovir dipivoxil (ADV) Solid lipid nanoparticles (SLN) Octadecylamine-fluorescein isothiocynate (ODA-FITC) Hepatitis B virus (HBV)
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Storage Stability of Alpha-Lipoic Acid-loaded Lipid Nanoparticles
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作者 唐金国 夏强 刘光煜 《过程工程学报》 CAS CSCD 北大核心 2010年第2期332-338,共7页
Alpha-lipoic acid-loaded lipid nanoparticles(ALA-LNs) were prepared by high pressure homogenization method.The influences of storage conditions such as time and temperature on the physical and chemical storage stabili... Alpha-lipoic acid-loaded lipid nanoparticles(ALA-LNs) were prepared by high pressure homogenization method.The influences of storage conditions such as time and temperature on the physical and chemical storage stability of ALA-LNs were studied in details.The stability was evaluated by particle size and polydispersity index,morphology of ALA-LNs,and capacity of ALA loading.The dilution and pH stability of ALA-LNs suspensions were also studied.After three months storage,the mean size of ALA-LNs at 4 and 40 ℃ was increased by 2.68% and 3.62% compared with the original size,respectively.ALA-LNs stored at 40 ℃ had ellipsoid shape and the mean size was about 152 nm(SD=23.6).The loading capacity of ALA at 40 ℃ was much higher than those stored at other two temperatures.The good dilution and pH stability were also demonstrated.The sample had good fluidity even at 4 ℃. 展开更多
关键词 alpha-lipoic acid lipid nanoparticles storage stability particle size particle morphology
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Bovine Serum Albumin Loaded Solid Lipid Nanoparticles Prepared by Double Emulsion Method
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作者 LI Zhen LI Xin-wei ZHENG Li-qiang LIN Xiao-hong GENG Fei YU Li 《Chemical Research in Chinese Universities》 SCIE CAS CSCD 2010年第1期136-141,共6页
Solid lipid nanoparticles loaded with bovine serum albumin(BSA) were prepared by a double emulsion method. As the mass fraction of the model drug BSA increased from 0 to 15%, the particle size gradually increased. T... Solid lipid nanoparticles loaded with bovine serum albumin(BSA) were prepared by a double emulsion method. As the mass fraction of the model drug BSA increased from 0 to 15%, the particle size gradually increased. The physical stability of the nanoparticles was investigated by zeta potential measurement and they were shown to be quite stable. Fluorescence spectroscopy confirmed that the loaded position of BSA was on the interface between the inner aqueous phase and the solid lipid phase. Both Fourier-transform infrared spectroscopy and circular dichroism spectra indicate that BSA in the nanoparticles was not destroyed, but the secondary structure was disrupted slightly. 展开更多
关键词 Solid lipid nanoparticle Double emulsion Bovine serum albumin Drug model
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Evaluation of atherosclerotic lesions in cholesterol-fed mice during treatment with paclitaxel in lipid nanoparticles: a magnetic resonance imaging study
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作者 Aline D. Lima Ning Hua +1 位作者 Raul C. Maranhao James A. Hamilton 《The Journal of Biomedical Research》 CAS CSCD 2017年第2期116-121,共6页
Cholesterol-core nanoparticles (LDE) have been shown to be recognized by low-density lipoprotein receptors (LDLR) after administration; therefore, LDE is an ideal vehicle to deliver drug with targeting property. P... Cholesterol-core nanoparticles (LDE) have been shown to be recognized by low-density lipoprotein receptors (LDLR) after administration; therefore, LDE is an ideal vehicle to deliver drug with targeting property. Paclitaxel, when incorporated into LDE, promotes atherosclerosis regression with reduced drug toxicity in rabbits through LDLR. Here, we tested whether LDE-paclitaxel could still be effective in reducing diet-induced atherosclerosis in a mouse model without LDLR. Nineteen LDLR knockout male mice were fed 1% cholesterol for 12 weeks. Then, 12 animals received 4-weekly intraperitoneal LDE-paclitaxel (4 mg/kg) while 7 controls received saline solution. On week 12 and 16, in vivo MR/of the aortic roots was performed. Aorta macroscopy was made after euthanasia. Reduction ofatherosclerotic lesions was observed. LDE-paclitaxel treatment resulted in reduction of wall area (14%) and stenosis (22%) by MR/and 33% by macroscopy. Thus, LDE-paclitaxel may produce pharmacological effects through LDE uptake by mechanisms other than LDLR. 展开更多
关键词 atherosclerosis treatment lipid solid nanoparticles emulsions PACLITAXEL MRI drug targeting
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β-Lactoglobulin stabilized lipid nanoparticles enhance oral absorption of insulin by slowing down lipolysis 被引量:1
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作者 Lu Li Suticha Chunta +3 位作者 Xianzi Zheng Haisheng He Wei Wu Yi Lu 《Chinese Chemical Letters》 SCIE CAS CSCD 2024年第4期287-291,共5页
Lipid-based nanocarriers have staged a remarkable comeback in the oral delivery of proteins and peptides, but delivery efficiency is compromised by lipolysis. β-Lactoglobulin(β-lg) stabilized lipid nanoparticles, in... Lipid-based nanocarriers have staged a remarkable comeback in the oral delivery of proteins and peptides, but delivery efficiency is compromised by lipolysis. β-Lactoglobulin(β-lg) stabilized lipid nanoparticles, including nanoemulsions(NE@β-lg) and nanocapsules(NC@β-lg), were developed to enhance the oral absorption of insulin by slowing down lipolysis due to the protection from β-lg. Cremophor EL stabilized nanoemulsions(NE@Cre-EL) were prepared and set as a control. The lipid nanoparticles produced mild and sustained hypoglycemic effects, amounting to oral bioavailability of 3.0% ± 0.3%, 7.0% ± 1.1%, and7.7% ± 0.8% for NE@Cre-EL, NE@β-lg, and NC@β-lg, respectively. Aggregation-caused quenching(ACQ)probes enabled the identification of intact nanoparticles, which were used to investigate the in vivo and intracellular fates of the lipid nanoparticles. In vitro digestion/lipolysis and ex vivo imaging confirmed delayed lipolysis from β-lg stabilized lipid nanoparticles. NC@β-lg was more resistant to intestinal lipolysis than NE@β-lg due to the Ca^(2+)-induced crosslinking. Live imaging revealed the transepithelial transport of intact nanoparticles and their accumulation in the liver. Cellular studies confirmed the uptake of intact nanoparticles. Slowing down lipolysis via food proteins represents a good strategy to enhance the oral absorption of lipid nanoparticles and thus co-formulated biomacromolecules. 展开更多
关键词 Β-LACTOGLOBULIN lipid nanoparticles Oral absorption INSULIN LIPOLYSIS Aggregation-caused quenching
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Modeling on in vivo disposition and cellular transportation of RNA lipid nanoparticles via quantum mechanics/physiologically-based pharmacokinetic approaches
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作者 Wei Wang Shiwei Deng +1 位作者 Jinzhong Lin Defang Ouyang 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2024年第10期4591-4607,共17页
The lipid nanoparticle(LNP)has been so far proven as a strongly effective delivery system for mRNA and siRNA.However,the mechanisms of LNP's distribution,metabolism,and elimination are complicated,while the transp... The lipid nanoparticle(LNP)has been so far proven as a strongly effective delivery system for mRNA and siRNA.However,the mechanisms of LNP's distribution,metabolism,and elimination are complicated,while the transportation and pharmacokinetics(PK)of LNP are just sparsely investigated and simply described.This study aimed to build a model for the transportation of RNA-LNP in Hela cells,rats,mice,and humans by physiologically based pharmacokinetic(PBPK)and quantum mechanics(QM)models with integrated multi-source data.LNPs with different ionizable lipids,particle sizes,and doses were modeled and compared by recognizing their critical parameters dominating PK.Some interesting results were found by the models.For example,the metabolism of ionizable lipids was first limited by the LNP disassembly rate instead of the hydrolyzation of ionizable lipids;the ability of RNA release from endosomes for three ionizable lipids was quantitively derived and can predict the probability of RNA release.Moreover,the biodegradability of three ionizable lipids was estimated by the QM method and the is generally consistent with the result of PBPK result.In summary,the transportation model of RNA LNP among various species for the first time was successfully constructed.Various in vitro and in vivo pieces of evidence were integrated through QM/PBPK multi-level modeling.The resulting new understandings are related to biodegradability,safety,and RNA release ability which are highly concerned issues of the formulation.This would benefit the design and research of RNA-LNP in the future. 展开更多
关键词 lipid nanoparticle RNA Ionizable lipid In vivo transportation Endosomal escape Metabolism Quantum mechanics Physiologically-based pharmacokinetics
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Lipid nanoparticles deliver mRNA to the blood-brain barrier
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作者 Yanina Kuzminich Avraham Shakked +13 位作者 Randi Calkins Sebastian Rudden Camille Jones Jessie Doan Bora Jang Elisa Schrader Echeverri Ryan Zenhausern Liming Lian David Loughrey Hannah E.Peck Rachelle Wiese Dorothy Koveal Philip J.Santangelo James E.Dahlman 《Nano Research》 SCIE EI CSCD 2024年第10期9126-9134,共9页
Lipid nanoparticles(LNPs)have delivered RNA to hepatocytes in patients after intravenous administration.These clinical data support efforts to design LNPs that transfect cells in the central nervous system(CNS).Howeve... Lipid nanoparticles(LNPs)have delivered RNA to hepatocytes in patients after intravenous administration.These clinical data support efforts to design LNPs that transfect cells in the central nervous system(CNS).However,delivery to the CNS has been difficult,in large part because quantifying on-target delivery alongside common off-target cell types in adult mice remains challenging.Here we report methods to isolate different cell types from the CNS,and subsequently present mRNA delivery readouts using a liver-detargeted LNP.These data suggest that LNPs without targeting ligands can transfect cerebral endothelial cells in mice after intravenous administration.Given the difficulty of crossing the blood-brain barrier,they also underscore the value of quantifying delivery in the CNS with cell-type resolution instead of whole-tissue resolution. 展开更多
关键词 lipid nanoparticle MRNA NANOMEDICINE central nervous system blood-brain barrier
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M1-polarized macrophage-derived cellular nanovesicle-coated lipid nanoparticles for enhanced cancer treatment through hybridization of gene therapy and cancer immunotherapy
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作者 Ha Eun Shin Jun-Hyeok Han +6 位作者 Seungyong Shin Ga-Hyun Bae Boram Son Tae-Hyung Kim Hee Ho Park Chun Gwon Park Wooram Park 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2024年第7期3169-3183,共15页
Optimum genetic delivery for modulating target genes to diseased tissue is a major obstacle for profitable gene therapy.Lipid nanoparticles(LNPs),considered a prospective vehicle for nucleic acid delivery,have demonst... Optimum genetic delivery for modulating target genes to diseased tissue is a major obstacle for profitable gene therapy.Lipid nanoparticles(LNPs),considered a prospective vehicle for nucleic acid delivery,have demonstrated efficacy in human use during the COVID-19 pandemic.This study introduces a novel biomaterial-based platform,M1-polarized macrophage-derived cellular nanovesicle-coated LNPs(M1-C-LNPs),specifically engineered for a combined gene-immunotherapy approach against solid tumor.The dual-function system of M1-C-LNPs encapsulates Bcl2-targeting siRNA within LNPs and immune-modulating cytokines within M1 macrophage-derived cellular nanovesicles(M1-NVs),effectively facilitating apoptosis in cancer cells without impacting T and NK cells,which activate the intratumoral immune response to promote granule-mediating killing for solid tumor eradication.Enhanced retention within tumor was observed upon intratumoral administration of M1-C-LNPs,owing to the presence of adhesion molecules on M1-NVs,thereby contributing to superior tumor growth inhibition.These findings represent a promising strategy for the development of targeted and effective nanoparticle-based cancer genetic-immunotherapy,with significant implications for advancing biomaterial use in cancer therapeutics. 展开更多
关键词 Genetic-immunotherapy M1 macrophage-derived cellular nanovesicles lipid nanoparticles(LNPs) Gene therapy siRNA Cancer immunotherapy Solid tumor Tumor microenvironment(TME)
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