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.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.
5. Investigation and research on ticks carrying spotted fever group rickettsia in the border area of Tumen River Basin
Jixu LI ; Roh JONG-YUL ; Park WON-LL ; Wen PIAO ; Guangjun JIN ; Zhonggao WU ; Zhenhai SONG ; Shenghuan QUAN ; Guangming PIAO ; Hao SONG ; Cho SHIN-HYEONG
Chinese Journal of Preventive Medicine 2019;53(11):1130-1135
Objective:
To understand the situation and genotype distribution of spotted fever group rickettsia (SFGR) in the border area of Tumen River Basin in free ticks in Yanbian Korean Autonomous Prefecture (Yanbian Prefecture), Jilin Province.
Methods:
From April to September, 2017, ticks were collected using flagging method from Hunchun, Tumen, Helong and Longjing cities in the Tumen River basin of Yanbian Prefecture.
6.Investigation and research on ticks carrying spotted fever group rickettsia in the border area of Tumen River Basin
Jixu LI ; Roh JONG?YUL ; Park WON?LL ; Wen PIAO ; Guangjun JIN ; Zhonggao WU ; Zhenhai SONG ; Shenghuan QUAN ; Guangming PIAO ; Hao SONG ; Cho SHIN?HYEONG
Chinese Journal of Preventive Medicine 2019;53(11):1130-1135
Objective To understand the situation and genotype distribution of spotted fever group rickettsia (SFGR) in the border area of Tumen River Basin in free ticks in Yanbian Korean Autonomous Prefecture (Yanbian Prefecture), Jilin Province. Methods From April to September, 2017, ticks were collected using flagging method from Hunchun, Tumen, Helong and Longjing cities in the Tumen River basin of Yanbian Prefecture. Outer membrane protein A (ompA) was detected by Polymerase Chain Reaction (PCR), then, the species were identified by gene sequencing and analyzed systematically. The positive rate of pools and MIR(minimum infection rate per 100 ticks,MIR) of SFGR were calculated, and the difference of positive rate of pools among ticks with different characteristics was compared by Chi?square test. Results A total of 3 079 ticks were collected and divided into 536 pools. The positive rate of pools of SFGR nucleic acid was 39.7% (213 pools). The MIR of SFGR was 6.9%.The positive rate of pools of SFGR in Dermacentor silvarum, Haemaphysalis concinna, Haemaphysalis japonica, Haemaphysalis longicornis and Ixodes persulcatus were 80.4% (41/51), 14.0% (25/179), 20.2% (18/89), 78.9% (101/128) and 25.9% (21/81), and the difference was statistically significant (P<0.001). There was statistical difference in the positive rate of pools of SFGR in developmental stages of ticks (P<0.001); the positive rate of pools of female adults, male adults, nymph and larvae were 36.4% (95/261), 34.2% (67/196), 56.3% (40/71) and 7/8, and the MIR was 7.9%, 7.7%, 4.9% and 3.5%. The five genotype was detected which was Candidatus Rickettsia longicornii, Rickettsia raoultii, Rickettsia heilongjiangensis, Candidatus Rickettsia tarasevichiae,Rickettsia monacensis and have 98%-100% homology with known gene sequences. Candidatus Rickettsia longicornii, Rickettsia raoultii, Rickettsia heilongjiangensis and Candidatus Rickettsia tarasevichiae showed close evolutionary relationship with known specie (have 98%-100% homology with known gene sequences); Rickettsia monacensis showed Far from evolutionary relationship with known species (have 98% homology with known gene sequences). Conclusion SFGR infection of ticks is common in the border areas of the Tumen River Basin. There was high diversity in SFGR species and tick species in the areas surveyed.
7.Investigation and research on ticks carrying spotted fever group rickettsia in the border area of Tumen River Basin
Jixu LI ; Roh JONG?YUL ; Park WON?LL ; Wen PIAO ; Guangjun JIN ; Zhonggao WU ; Zhenhai SONG ; Shenghuan QUAN ; Guangming PIAO ; Hao SONG ; Cho SHIN?HYEONG
Chinese Journal of Preventive Medicine 2019;53(11):1130-1135
Objective To understand the situation and genotype distribution of spotted fever group rickettsia (SFGR) in the border area of Tumen River Basin in free ticks in Yanbian Korean Autonomous Prefecture (Yanbian Prefecture), Jilin Province. Methods From April to September, 2017, ticks were collected using flagging method from Hunchun, Tumen, Helong and Longjing cities in the Tumen River basin of Yanbian Prefecture. Outer membrane protein A (ompA) was detected by Polymerase Chain Reaction (PCR), then, the species were identified by gene sequencing and analyzed systematically. The positive rate of pools and MIR(minimum infection rate per 100 ticks,MIR) of SFGR were calculated, and the difference of positive rate of pools among ticks with different characteristics was compared by Chi?square test. Results A total of 3 079 ticks were collected and divided into 536 pools. The positive rate of pools of SFGR nucleic acid was 39.7% (213 pools). The MIR of SFGR was 6.9%.The positive rate of pools of SFGR in Dermacentor silvarum, Haemaphysalis concinna, Haemaphysalis japonica, Haemaphysalis longicornis and Ixodes persulcatus were 80.4% (41/51), 14.0% (25/179), 20.2% (18/89), 78.9% (101/128) and 25.9% (21/81), and the difference was statistically significant (P<0.001). There was statistical difference in the positive rate of pools of SFGR in developmental stages of ticks (P<0.001); the positive rate of pools of female adults, male adults, nymph and larvae were 36.4% (95/261), 34.2% (67/196), 56.3% (40/71) and 7/8, and the MIR was 7.9%, 7.7%, 4.9% and 3.5%. The five genotype was detected which was Candidatus Rickettsia longicornii, Rickettsia raoultii, Rickettsia heilongjiangensis, Candidatus Rickettsia tarasevichiae,Rickettsia monacensis and have 98%-100% homology with known gene sequences. Candidatus Rickettsia longicornii, Rickettsia raoultii, Rickettsia heilongjiangensis and Candidatus Rickettsia tarasevichiae showed close evolutionary relationship with known specie (have 98%-100% homology with known gene sequences); Rickettsia monacensis showed Far from evolutionary relationship with known species (have 98% homology with known gene sequences). Conclusion SFGR infection of ticks is common in the border areas of the Tumen River Basin. There was high diversity in SFGR species and tick species in the areas surveyed.
8.Diagnostic value of MSCT in cystic lung cancer with ground glass opacity
Chuyi CAI ; Hao GU ; Guangyou HE ; Junjie FANG ; Jiapei SHI ; Zhonggao JIN
Journal of Practical Radiology 2018;34(2):203-206
Objective To study the diagnostic value of MSCT in cystic lung cancer with ground glass opacity(GGO),and improve understanding of the disease as well as diagnostic accuracy.Methods 2 1 cases of pathologically confirmed cystic lung cancer with GGO were analyzed retrospectively,all patients were examined by MSCT.CT features of the GGO and the cysts,including bronchovascular convergence sign,speculation sign,pleural indentation sign,lobulation,thickness and uniformity of the cyst wall,septa and the location of the lesion were analyzed.Results The image findings of the 21 cases of the cystic lung cancer with GGO included:bronchovasular convergence sign in 6 cases(28.6%),speculation sign in 10 cases(47.7%),pleural indentation sign in 12 cases(57.1%),lobulation in 8 cases(38.1%),10 cases(47.7%)showed pure GGO.The cyst wall was(1.7±0.9)mm in thickness and the cyst was (13.2±7.0)mm in diameter.Cyst wall was uniform in 9 cases(42.9%),septa was seen in 14 cases(66.7%),cysts of 16 cases(76.1%)were located in the upper lobes of the lung,1 case(4.7%)had distinctly mediastinal lymph node metastasis.Air-fluid lever,mural nodule or intrapulmonary metastasis were not present in any of the cases.Conclusion The majority of the cystic lung cancer with GGO are adenocarcinoma.In addition of the interference of its prominent cystic features on MSCT,the cystic lung cancer have characteristics of lung cancer with GGO.By analyzing its CT features,diagnostic accuracy can be improved before operation.
9.The value of MSCT in differentiating low-or high-risk thymomas and thymic carcinomas with maximum diameter equal or less than 3 cm
Aijing LI ; Zhonggao JIN ; Yuning PAN ; Yinhua JIN ; Yijiao WU ; Hongbin ZHANG ; Jianjun ZHENG
Journal of Practical Radiology 2017;33(10):1524-1527,1568
Objective To evaluate the diagnostic value of MSCT in the differentiation of thymic epithelial tumours (TET)with the maximum diameter equal or less than 3 cm.Methods A retrospective analysis of pathological and imaging data of 56 patients with pathologically confirmed TET with the maximum diameter equal or less than 3 cm was performed.According to the 2004 WHO classification,56 TETs were classified as low-risk thymomas(types A/AB/B1),high-risk thymomas (types B2/B3)and thymic carcinomas (type C).The CT manifestations of TET in each group,including shape of tumor,tumor edge (smooth or spiculate protuberance), presence of small nodule around tumor,enhancement degree,pleura invasion and fat space around tumor,were analyzed retrospectively.The differences in the CT manifestations among three types were compared using chi-square test.If the sample number was too small, Fisher 's exact test was used.Results Compared with high-risk thymomas (23 cases)and thymic carcinomas (6 cases),regular round shape was more often observed in low-risk thymomas (27 cases)(χ2 =73,P <0.001;χ2 =116,P <0.001)and the mediastinum-lung interface was more likely to bulge (χ2 = 3.41,P =0.046;χ2 =7.39,P =0.01).Blurred edge,spiculate protuberance and pleural invasion and so on were significantly more common in high-risk thymomas and thymic carcinomas (P <0.001)and they were the most common in thymic carcinomas (χ2 =11.5,P =0.009).There was a significant difference between type B2 thymomas and thymic carcinomas (χ2 =31.52, P <0.001),however there was no significant difference between type B3 thymomas and thymic carcinomas (χ2 =6.96,P =0.07). Conclusion MSCT can accurately show the shape of tumor,tumor edge,presence of small nodule around tumor,enhancement degree,pleura invasion,which can predict the histologic type of thymomas and also can provide information for preoperative diagnosis and prognosis evaluation.
10.Nanocarrier-mediated co-delivery of chemotherapeutic drugs and gene agents for cancer treatment.
Lin KANG ; Zhonggao GAO ; Wei HUANG ; Mingji JIN ; Qiming WANG
Acta Pharmaceutica Sinica B 2015;5(3):169-175
The efficacy of chemotherapeutic drug in cancer treatment is often hampered by drug resistance of tumor cells, which is usually caused by abnormal gene expression. RNA interference mediated by siRNA and miRNA can selectively knock down the carcinogenic genes by targeting specific mRNAs. Therefore, combining chemotherapeutic drugs with gene agents could be a promising strategy for cancer therapy. Due to poor stability and solubility associated with gene agents and drugs, suitable protective carriers are needed and have been widely researched for the co-delivery. In this review, we summarize the most commonly used nanocarriers for co-delivery of chemotherapeutic drugs and gene agents, as well as the advances in co-delivery systems.

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