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Wei-Jie Cheng,1,* Shyr-Yi Lin,2,3,* Kuo-Hsiang Chuang,4,5,* Michael Chen,4 Hsiu-O Ho,1 Ling-Chun Chen,6 Chien-Ming Hsieh,1 Ming-Thau Sheu1 1School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan; 2Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 3Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 4Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan; 5PhD Program in Clinical Drug Development of Chinese Herbal Medicine, Taipei Medical University, Taipei, Taiwan; 6Department of Biotechnology and Pharmaceutical Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan*These authors contributed equally to this workCorrespondence: Chien-Ming Hsieh; Ming-Thau Sheu, Email cmhsieh@tmu.edu.tw; mingsheu@tmu.edu.twIntroduction: Approximately 15%~30% of breast cancers have gene amplification or overexpression of the human epidermal growth factor receptor 2 (HER2), resulting in the chemotherapy resistance, a more-aggressive phenotype and poor prognosis.Methods: We propose a strategy of nanocarriers co-loaded with docetaxel (DTX) and pictilisib (PIC) at a synergistic ratio and non-covalently bound with dual anti-HER2 epitopes bispecific antibodies (BsAbs: anti-HER2-IV/methoxy-polyethylene glycol (mPEG) and anti-HER2-II/methoxy-PEG) for synergistic targeting to overcome the therapeutic dilemmas of the resistance for HER2-targetable chemodrugs. DTX/PIC-loaded nanocarriers (D/P_NCs) were prepared with single emulsion methods and characterized using dynamic light scattering analysis, and the drug content was assayed by high-performance liquid chromatographic method. The integrity and function of BsABs were evaluated using sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) and enzyme-linked immunosorbent assay (ELISA). The in vitro cell studies and in vivo breast t

Wen-Ting Cheng,1,&ast; Hsiu-O Ho,1,&ast; Shyr-Yi Lin,2,3 Der-Zen Liu,4 Ling-Chun Chen,5 Ming-Thau Sheu1 1School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan, Republic of China; 2Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, Republic of China; 3Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China; 4Graduate Institute of Biomedical Materials and Engineering, Taipei Medical University, Taipei, Taiwan, Republic of China; 5Department of Biotechnology and Pharmaceutical Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan, Republic of China&ast;These authors contributed equally to this workCorrespondence: Ming-Thau SheuSchool of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 11031, Taiwan, Republic of ChinaTel/Fax +886 2 2377 1942Email mingsheu@tmu.edu.twLing-Chun ChenDepartment of Biotechnology and Pharmaceutical Technology, Yuanpei University of Medical Technology, No. 306, Yuanpei Street, Hsinchu, 30015, Taiwan, Republic of ChinaTel/Fax +886 2 2377 1942Email d8801004@mail.ypu.edu.twPurpose: Therapeutic efficacy of pancreatic adenocarcinomas (PACs) with combined therapy of carfilzomib (CFZ) and paclitaxel (PTX) co-loaded in human serum albumin (HSA) nanoparticles (NPs) was examined.Methods: CFZ and PTX were encapsulated individually or combined into HSA NPs by a simple reverse self-assembly method developed to achieve an optimal combination ratio for synergistic therapy. CFZ or/and PTX loaded HSA nanoparticles were physically characterized and the evaluation of combination index, drug release, pharmacokinetic, anti-tumor, and biodistribution studies were conducted.Results: All resultant drug-loaded HSA NPs were spherical with a particle size of < 150 nm and a zeta potential of − 21.1∼− 23.0 mV. Drug loadin

Wei-Jie Cheng,1,* Shyr-Yi Lin,2,3,* Michael Chen,4 Ling-Chun Chen,5 Hsiu-O Ho,1 Kuo-Hsiang Chuang,4,6 Ming-Thau Sheu1 1School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan; 2Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 3Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 4PhD Program in Clinical Drug Development of Chinese Herbal Medicine, Taipei Medical University, Taipei, Taiwan; 5Department of Biotechnology and Pharmaceutical Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan; 6Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan*These authors contributed equally to this workCorrespondence: Kuo-Hsiang Chuang; Ming-Thau Sheu Email khchuang@tmu.edu.tw; mingsheu@tmu.edu.twPurpose: This study was aimed at developing the trispecific antibodies (anti-EGFR/anti-FAP/anti-mPEG, TsAb) or dual bispecific antibodies (anti-EGFR/anti-mPEG and anti-FAP/anti-mPEG) docetaxel (DTX)-loaded mPEGylated lecithin-stabilized micelles (mPEG-lsbPMs) for improving the targeting efficiency and therapeutic efficacy.Methods: mPEG-lsbPMs were simply prepared via thin film method. The trispecific antibodies or bispecific antibodies bound the mPEG-lsbPMs by anti-mPEG Fab fragment. The formulations were characterized by DLS and TEM; in vitro and in vivo studies were also conducted to evaluate the cellular uptake, cell cytotoxicity and therapeutic efficacy.Results: The particle sizes of mPEG-lsbPMs with or without the antibodies were around 100 nm; the formulations showed high encapsulation efficiencies of 97.12%. The TsAb and dual bispecific antibodies were fabricated and demonstrated their targeting ability. Two EGFR-overexpressed cell lines (HT-29 and MIA PaCa-2) were co-cultured with FAP-overexpressed WS1 cells (HT-29/WS1; MIA PaCa-2/WS1) to mimic a tumor coexisting in the tumor

Hong-Liang Lin,1 Wen-Ting Cheng,2 Ling-Chun Chen,3 Hsiu-O Ho,2 Shyr-Yi Lin,4,5 Chien-Ming Hsieh2 1School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, Republic of China; 2School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan, Republic of China; 3Department of Biotechnology and Pharmaceutical Technology, Yuanpei University of Medical Technology, Hsinchu 30015, Taiwan, Republic of China; 4Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan, Republic of China; 5Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan, Republic of ChinaCorrespondence: Shyr-Yi Lin; Chien-Ming Hsieh 250 Wu-Hsing Street, Taipei 11031, Taiwan, Republic of ChinaTel +886-2-27361661 ext 6112Fax +886-2-23771942Email sylin@tmu.edu.tw; cmhsieh@tmu.edu.twObjective: This study was intended to utilize lecithin-based mixed polymeric micelles (lbMPMs) for enhancing the solubility and bioavailability of honokiol and magnolol to resolve the hindrance of their extreme hydrophobicity on the clinical applications.Methods: Lecithin was selected to increase the volume of the core of lbMPMs, thereby providing a greater solubilization capacity. A series of amphiphilic polymers (sodium deoxycholate [NaDOC], Cremophor®, and Pluronic® series) were included with lecithin for screening and optimization.Results: After preliminary evaluation and subsequentially optimization, two lbMPMs formulations composed of honokiol/magnolol:lecithin:NaDOC (lbMPMs[NaDOC]) and honokiol/magnolol:lecithin:PP123 (lbMPMs[PP123]) in respective ratios of 6:2:5 and 1:1:10 were optimally obtained with the mean particle sizes of 80– 150 nm, encapsulation efficacy (EEs) of > 90%, and drug loading (DL) of > 9.0%. These lbMPMs efficiently stabilized honokiol/magnolol in phosphate-buffered