This study aimed to encapsulate an anti-VEGF nanobody (Nb) within niosome nanoparticles (NNPs) to enhance its circulation half life. Key parameters such as encapsulation efficiency, stability, Nb release, cytotoxicity, and cell migration inhibition in HUVEC cells were evaluated, along with pharmacokinetic studies in mice. Nb-loaded NNPs (Nb-NNPs) were successfully prepared with an encapsulation efficiency of 78.3 ± 3.2% and demonstrated stability over one month. assays revealed that Nb-NNPs enhanced cytotoxicity and significantly reduced cell migration in HUVEC cells compared to free Nb ( < 0.05). Pharmacokinetic studies in mice demonstrated a dramatically reduced elimination rate constant (0.025 h vs. 0.843 h) and an extended terminal half life (27.721 h vs. 0.822 h), indicating slower clearance and prolonged systemic presence. In conclusion, these findings underscore the potential of Nb-NNPs to provide sustained and potent therapeutic effects, contributing valuable insights for advancing targeted therapeutic strategies.
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http://dx.doi.org/10.1080/02652048.2024.2443435 | DOI Listing |
J Microencapsul
December 2024
Venom and Biotherapeutics Molecules Laboratory, Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
This study aimed to encapsulate an anti-VEGF nanobody (Nb) within niosome nanoparticles (NNPs) to enhance its circulation half life. Key parameters such as encapsulation efficiency, stability, Nb release, cytotoxicity, and cell migration inhibition in HUVEC cells were evaluated, along with pharmacokinetic studies in mice. Nb-loaded NNPs (Nb-NNPs) were successfully prepared with an encapsulation efficiency of 78.
View Article and Find Full Text PDFElife
June 2024
MOE Key Laboratory of Bioinformatics, State Key Laboratory of Molecular Oncology, School of Pharmaceutical Sciences, Tsinghua University, Beijing, China.
Accurate prediction of the structurally diverse complementarity determining region heavy chain 3 (CDR-H3) loop structure remains a primary and long-standing challenge for antibody modeling. Here, we present the H3-OPT toolkit for predicting the 3D structures of monoclonal antibodies and nanobodies. H3-OPT combines the strengths of AlphaFold2 with a pre-trained protein language model and provides a 2.
View Article and Find Full Text PDFInt J Pharm
June 2024
Biotechnology Research Centre, Venom and Biotherapeutics Molecules Laboratory, Pasteur Institute of Iran, Iran. Electronic address:
Blindness in the elderly is often caused by age-related macular degeneration (AMD). The advanced type of AMD known as neovascular AMD (nAMD) has been linked to being the predominant cause of visual impairment in these people. Multiple neovascular structures including choroidal neovascular (CNV) membranes, fluid exudation, hemorrhages, and subretinal fibrosis, are diagnostic of nAMD.
View Article and Find Full Text PDFBioeng Transl Med
March 2024
School of Pharmaceutical Sciences, Beijing Frontier Research Center for Biological Structure, and Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education) Tsinghua University Beijing People's Republic of China.
Intravitreal (IVT) injection of anti-vascular endothelial growth factor (anti-VEGF) has greatly improved the treatment of many retinal disorders, including wet age-related macular degeneration (wAMD), which is the third leading cause of blindness. However, frequent injections can be difficult for patients and may lead to various risks such as elevated intraocular pressure, infection, and retinal detachment. To address this issue, researchers have found that IVT injection of anti-VEGF proteins at their maximally viable concentration and dose can be an effective strategy.
View Article and Find Full Text PDFBioeng Transl Med
November 2023
School of Pharmaceutical Sciences, Beijing Advanced Innovation Center for Structural Biology, and Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education) Tsinghua University Beijing People's Republic of China.
Wet age-related macular degeneration (wet AMD) is the most common cause of blindness, and chronic intravitreal injection of anti-vascular endothelial growth factor (VEGF) proteins has been the dominant therapeutic approach. Less intravitreal injection and a prolonged inter-injection interval are the main drivers behind new wet AMD drug innovations. By rationally engineering the surface residues of a model anti-VEGF nanobody, we obtained a series of anti-VEGF nanobodies with identical protein structures and VEGF binding affinities, while drastically different crystallization propensities and crystal lattice structures.
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