1.Versatile flexible micelles integrating mucosal penetration and intestinal targeting for effectively oral delivery of paclitaxel.
Chao LIU ; Wei LIU ; Yanhong LIU ; Hongxia DUAN ; Liqing CHEN ; Xintong ZHANG ; Mingji JIN ; Minhu CUI ; Xiuquan QUAN ; Libin PAN ; Jiachun HU ; Zhonggao GAO ; Yan WANG ; Wei HUANG
Acta Pharmaceutica Sinica B 2023;13(8):3425-3443
The extremely low bioavailability of oral paclitaxel (PTX) mainly due to the complicated gastrointestinal environment, the obstruction of intestinal mucus layer and epithelium barrier. Thus, it is of great significance to construct a coordinative delivery system which can overcome multiple intestinal physicochemical obstacles simultaneously. In this work, a high-density PEGylation-based glycocholic acid-decorated micelles (PTX@GNPs) was constructed by a novel polymer, 9-Fluorenylmethoxycarbonyl-polyethylene glycocholic acid (Fmoc-PEG-GCA). The Fmoc motif in this polymer could encapsulate PTX via π‒π stacking to form the core of micelles, and the low molecular weight and non-long hydrophobic chain of Fmoc ensures the high-density of PEG. Based on this versatile and flexible carriers, PTX@GNPs possess mucus trapping escape ability due to the flexible PEG, and excellent intestine epithelium targeting attributed to the high affinity of GCA with apical sodium-dependent bile acid transporter. The in vitro and in vivo results showed that this oral micelle could enhance oral bioavailability of PTX, and exhibited similar antitumor efficacy to Taxol injection via intravenous route. In addition, oral PTX@GNPs administered with lower dosage within shorter interval could increase in vivo retention time of PTX, which supposed to remodel immune microenvironment and enhance oral chemotherapy efficacy by synergistic effect.
2.Research advances in peptide‒drug conjugates.
Liming GONG ; Heming ZHAO ; Yanhong LIU ; Hao WU ; Chao LIU ; Shuangyan CHANG ; Liqing CHEN ; Mingji JIN ; Qiming WANG ; Zhonggao GAO ; Wei HUANG
Acta Pharmaceutica Sinica B 2023;13(9):3659-3677
Peptide‒drug conjugates (PDCs) are drug delivery systems consisting of a drug covalently coupled to a multifunctional peptide via a cleavable linker. As an emerging prodrug strategy, PDCs not only preserve the function and bioactivity of the peptides but also release the drugs responsively with the cleavable property of the linkers. Given the ability to significantly improve the circulation stability and targeting of drugs in vivo and reduce the toxic side effects of drugs, PDCs have already been extensively applied in drug delivery. Herein, we review the types and mechanisms of peptides, linkers and drugs used to construct PDCs, and summarize the clinical applications and challenges of PDC drugs.
3.The influence of the gut microbiota on the bioavailability of oral drugs.
Xintong ZHANG ; Ying HAN ; Wei HUANG ; Mingji JIN ; Zhonggao GAO
Acta Pharmaceutica Sinica B 2021;11(7):1789-1812
Due to its safety, convenience, low cost and good compliance, oral administration attracts lots of attention. However, the efficacy of many oral drugs is limited to their unsatisfactory bioavailability in the gastrointestinal tract. One of the critical and most overlooked factors is the symbiotic gut microbiota that can modulate the bioavailability of oral drugs by participating in the biotransformation of oral drugs, influencing the drug transport process and altering some gastrointestinal properties. In this review, we summarized the existing research investigating the possible relationship between the gut microbiota and the bioavailability of oral drugs, which may provide great ideas and useful instructions for the design of novel drug delivery systems or the achievement of personalized medicine.
4.Recent advances in drug delivery systems for targeting cancer stem cells.
Hongxia DUAN ; Yanhong LIU ; Zhonggao GAO ; Wei HUANG
Acta Pharmaceutica Sinica B 2021;11(1):55-70
Cancer stem cells (CSCs) are a subpopulation of cancer cells with functions similar to those of normal stem cells. Although few in number, they are capable of self-renewal, unlimited proliferation, and multi-directional differentiation potential. In addition, CSCs have the ability to escape immune surveillance. Thus, they play an important role in the occurrence and development of tumors, and they are closely related to tumor invasion, metastasis, drug resistance, and recurrence after treatment. Therefore, specific targeting of CSCs may improve the efficiency of cancer therapy. A series of corresponding promising therapeutic strategies based on CSC targeting, such as the targeting of CSC niche, CSC signaling pathways, and CSC mitochondria, are currently under development. Given the rapid progression in this field and nanotechnology, drug delivery systems (DDSs) for CSC targeting are increasingly being developed. In this review, we summarize the advances in CSC-targeted DDSs. Furthermore, we highlight the latest developmental trends through the main line of CSC occurrence and development process; some considerations about the rationale, advantages, and limitations of different DDSs for CSC-targeted therapies were discussed.
5.Multifunctional oral delivery systems for enhanced bioavailability of therapeutic peptides/proteins.
Ying HAN ; Zhonggao GAO ; Liqing CHEN ; Lin KANG ; Wei HUANG ; Mingji JIN ; Qiming WANG ; You Han BAE
Acta Pharmaceutica Sinica B 2019;9(5):902-922
In last few years, therapeutic peptides/proteins are rapidly growing in drug market considering their higher efficiency and lower toxicity than chemical drugs. However, the administration of therapeutic peptides/proteins is mainly limited in parenteral approach. Oral therapy which was hampered by harsh gastrointestinal environment and poorly penetrating epithelial barriers often results in low bioavailability (less than 1%-2%). Therefore, delivery systems that are rationally designed to overcome these challenges in gastrointestinal tract and ameliorate the oral bioavailability of therapeutic peptides/proteins are seriously promising. In this review, we summarized various multifunctional delivery systems, including lipid-based particles, polysaccharide-based particles, inorganic particles, and synthetic multifunctional particles that achieved effective oral delivery of therapeutic peptides/proteins.
6.Preservation technique of internal iliac artery in performing endovascular aortic repair
Yongquan GU ; Yiren LIU ; Lianrui GUO ; Jianming GUO ; Zhu TONG ; Xixiang GAO ; Jian ZHANG ; Zhonggao WANG
Journal of Interventional Radiology 2017;26(2):184-187
Endovascular aortic repair (EVAR) has been the main treatment means for abdominal aortic aneurysm.It has become an expert consensus that in the case of abdominal aortic aneurysm that is complicated by iliac aneurysm,the preservation of internal iliac artery is necessary because it can prevent the occurrence of gluteal muscle ischemnia,sigmoid ischemia,male sexual dysfunction and other complications.In recent years,with the continuous updating of the endovascular devices it has become possible to retain the internal iliac artery in the performance of EVAR.At present,the reconstruction of internal iliac artery in EVAR includes a variety of techniques,including intraluminal iliac branched device (IBD) technique,sandwich technique,common iliac artery covered-stent bell-bottom (BBT) technique,external iliac artery-internal iliac artery intraluminal shunt technique (reverse chimney technique),and spring coil embolism technique.This article aims to make a summary of all the above mentioned techniques.
7.Percutaneous endovascular aorta repair under local anesthesia with no use of any contrast agent for abdominal aortic aneurysm: initial experience in one patient
Zhu TONG ; Yongquan GU ; Lianrui GUO ; Xixiang GAO ; Jianming GUO ; Chengchao ZHANG ; Liqiang LI ; Jian ZHANG ; Zhonggao WANG
Journal of Interventional Radiology 2017;26(7):594-596
Objective To evaluate the feasibility of endovascular aortic repair (EVAR) under local anesthesia without using any contrast agent for abdominal aortic aneurysm in patients with high allergic risk to contrast agent.Methods Under local anesthesia and with no use of any contrast,percutaneous EVAR was performed in a patient with abdominal aortic aneurysm who carried high allergic risk to contrast agent.Results Percutaneous EVAR was successfully accomplished.Postoperative follow-up MRI examination showed that the abdominal aortic aneurysm was completely isolated with no endoleak.The blood flow was unobstructed in the covered stent,and bilateral renal arteries were well visualized.Conclusion For the treatment of abdominal aortic aneurysm in patients who are highly allergic to contrast agent and who have contraindications to general anesthesia,percutaneous EVAR performed under local anesthesia and using no contrast agent is safe and effective.Strict observation of indications and sufficient preoperative evaluation of clinical conditions is the key to ensure a successful operation.
8.Preliminary study on selective usage of embolic protection device during SilverHawk atherectomy to prevent distal embolization
Lianrui GUO ; Yongquan GU ; Lixing QI ; Shijun CUI ; Yingfeng WU ; Zhu TONG ; Jianming GUO ; Yixia QI ; Shengjia YANG ; Xixiang GAO ; Jian ZHANG ; Zhonggao WANG
Journal of Chinese Physician 2017;19(12):1768-1771
Objective To explore the clinical effectiveness and safety of selective usage of embolic protection device to prevent distal embolization during SilverHawk atherectomy for atherosclerotic femoropo-pliteal artery disease. Methods From Jan 2014 to December 2015, 45 femoropopliteal artery atherosclerot-ic patients were treated with SilverHawk atherectomy and selective embolic protection device (EPD). The indication for EPD was instent restenosis, highly calcified lesion, suspicious of thrombosis, ulcerated le-sion, and single below-the-knee runoff. All cases who met the indication were treated with atherectomy and EPD, and those who did not meet the indication were treated with or without EPD according to the patient's choice. The embolic related complications were analyzed. Results Twenty three out of 45 patients who met the EPD indication were all treated with SilverHawk atherectomy under EPD protection, filter captured deb-ris in 17 patients (73. 9%) of the patients. The other 22 patients who did not meet the indication were di-vided into 2 groups according to the patient's choice of EPD usage, 11 were treated by atherectomy with EPD and 11 without EPD. One case out of 11 unindicated patients without EPD suffered a tibioperoneal trunk embolization and restored with catheter aspiration. For 1/11 (9. 1%) unindicated cases with EPD protec-tion, the filter captured embolization. There was a significant difference of distal embolization rate between the indicated and unindicated patients (χ2 =19. 368,P =0. 000). All filters were retrieved successfully without any distal embolization and any complications except arterial spasm occurred in 2 patients and re-stored well with nitroglycerin. Conclusions It is safe and effective for selective usage of embolic protection device to prevent distal embolization during SilverHawk atherectomy for atherosclerotic femoropopliteal artery disease.
9.Preliminary study on atherectomy for treatment of Tosaka class Ⅲ in-stent restenosis in femoropo-pliteal artery
Xixiang GAO ; Yongquan GU ; Lianrui GUO ; Zhu TONG ; Yang LI ; Jianming GUO ; Jianxin LI ; Jian ZHANG ; Zhonggao WANG
Journal of Chinese Physician 2017;19(12):1776-1778
Objective o investigate the clinical efficacy of atherectomy in the treatment of Tosaka class Ⅲ in-stent restenosis in the femoropopliteal artery. Methods From June 2013 to December 2015, 33 restenotic lesions after femoropopliteal artery stenting were retrospectively analyzed by clinical information including technical success rate, incidence of complications, improvement of postoperative symptoms and objective indicators, and target vessel patency. Results To January 2016, twenty-eight cases were followed up. The average follow-up time was 17. 9 months. Five cases were lost. The follow-up rate was 84. 9%. The technical success rate was 100%. The patency rate was 79. 9% at 6 months and 65. 8% at 1 year after surgery. Conclusions Atherectomy is safe and effective for treatment of Tosaka classⅢin-stent restenosis in femoropopliteal artery with good short-term and medium-term efficacy.

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