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Overcoming oral insulin delivery barriers: application of cell penetrating peptide and silica-based nanoporous

Huining HE, Junxiao YE, Jianyong SHENG, Jianxin WANG, Yongzhuo HUANG, Guanyi CHEN, Jingkang WANG, Victor C YANG

《化学科学与工程前沿（英文）》 2013年 第7卷 第1期   页码 9-19 doi: 10.1007/s11705-013-1306-9

摘要： Oral insulin delivery has received the most attention in insulin formulations due to its high patient compliance and, more importantly, to its potential to mimic the physiologic insulin secretion seen in non-diabetic individuals. However, oral insulin delivery has two major limitations: the enzymatic barrier that leads to rapid insulin degradation, and the mucosal barrier that limits insulin’s bioavailability. Several approaches have been actively pursued to circumvent the enzyme barrier, with some of them receiving promising results. Yet, thus far there has been no major success in overcoming the mucosal barrier, which is the main cause in undercutting insulin’s oral bioavailability. In this review of our group’s research, an innovative silica-based, mucoadhesive oral insulin formulation with encapsulated-insulin/cell penetrating peptide (CPP) to overcome both enzyme and mucosal barriers is discussed, and the preliminary and convincing results to confirm the plausibility of this oral insulin delivery system are reviewed. In vitro studies demonstrated that the CPP-insulin conjugates could facilitate cellular uptake of insulin while keeping insulin’s biologic functions intact. It was also confirmed that low molecular weight protamine (LMWP) behaves like a CPP peptide, with a cell translocation potency equivalent to that of the widely studied TAT. The mucoadhesive properties of the produced silica-chitosan composites could be controlled by varying both the pH and composition; the composite consisting of chitosan (25 wt-%) and silica (75 wt-%) exhibited the greatest mucoadhesion at gastric pH. Furthermore, drug release from the composite network could also be regulated by altering the chitosan content. Overall, the universal applicability of those technologies could lead to development of a generic platform for oral delivery of many other bioactive compounds, especially for peptide or protein drugs which inevitably encounter the poor bioavailability issues.

关键词： insulin     cell penetrating peptide     mucoadhesive composites     oral delivery    

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A Double-Layer Polysaccharide Hydrogel (DPH) for the Enhanced Intestine-Targeted Oral Delivery of Probiotics

Wen-Can Huang,Wenjie Wang,Wei Wang,Yanan Hao,Changhu Xue,Xiangzhao Mao,

《工程（英文）》 doi: 10.1016/j.eng.2023.05.024

摘要： Transplantation of probiotics to the intestine can positively regulate the gut microbiota, thereby promoting the immune system and treating various diseases. However, the harsh gastrointestinal environment and short retention time in the gastrointestinal tract significantly limit the bioavailability and intestinal colonization of probiotics. Herein, we present a double-layer polysaccharide hydrogel (DPH) in the form of a double-layer structure composed of a carboxymethyl cellulose (CMCL) supramolecular inner layer and a dialdehyde alginate (DAA) cross-linked carboxymethyl chitosan (CMCS) outer layer. This double-layer structure allows DPH to encapsulate and deliver probiotics in a targeted manner within the body. In the stomach, the cage structure of the DPH is closed, and the outer layer absorbs surrounding liquids to form a barrier to protect the probiotics from gastric fluids. In the intestine, the cage structure opens and disintegrates, releasing the probiotics. Thus, DPH endows probiotics with excellent intestine-targeted delivery, improved oral bioavailability, enhanced gastrointestinal tract tolerance, and robust mucoadhesion capacity. The encapsulated probiotics exhibit almost unchanged bioactivity in the gastrointestinal tract before release, as well as improved oral delivery. In particular, probiotics encapsulated by DPH exhibit 100.1 times higher bioavailability and 10.6 times higher mucoadhesion than free probiotics in an animal model 48 h post-treatment. In addition, with a remarkable ability to survive and be retained in the intestine, probiotics encapsulated by DPH show excellent in vitro and in vivo competition with pathogens. Notably, DAA-mediated dynamic crosslinking not only maintains the overall integrity of the hydrogels but also controls the release timing of the probiotics. Thus, it is expected that encapsulated substances (probiotics, proteins, etc.) can be delivered to specific sites of the intestinal tract by means of DPH, by controlling the dynamic covalent crosslinking.

关键词： Polysaccharides     Chitosan     Hydrogels     Oral delivery     Intestine-targeted    

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Factors related to compliance with oral analgesic treatment of inpatients with chronic pain

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《医学前沿（英文）》 2015年 第9卷 第3期   页码 374-379 doi: 10.1007/s11684-015-0411-1

摘要：

This study aimed to determine the relationship between the different factors of analgesic therapy and the compliance of chronic pain inpatients. We prospectively investigated 100 consecutive inpatients with non-cancer chronic pain who were hospitalized to receive oral analgesic treatment in the Pain Department of West China Hospital from May 2013 to October 2013. Patients who completed the treatment plan were recorded as good compliance, whereas patients who partly completed or even refused the treatment were recorded as moderate or non-compliance, respectively. A total of 73 (73.7%), 17 (17.1%), and 9 (9.2%) patients showed good, moderate, and non-compliance, respectively. Univariate analyses showed significantly better compliance among farmers, patients educated in college or above, with family income of<3000 CNY, and with severe or moderate pain than those employed and unemployed (P=0.02), patients educated below college (P=0.013), with family income of≥3000 CNY (P=0.025), and with mild pain (P<0.001), respectively. Logistic regression analysis showed that the family income of≥3000 CNY (OR: 2.50, 95%CI: 1.65–4.51, P=0.021) and mild pain (OR: 1.27, 95%CI: 1.03–3.31, P=0.016) were associated with moderate or non-compliance with oral analgesic treatment. In conclusion, the low compliance with oral treatment of analgesics was found in Chinese inpatients with chronic pain and compliance was negatively associated with family income and degree of pain of patients.

关键词： chronic pain     inpatient     oral paregoric drugs     compliance    

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Oral product input to the GI tract: GIS an oral product performance technology

Gordon L. Amidon, Yasuhiro Tsume

《化学科学与工程前沿（英文）》 2017年 第11卷 第4期   页码 516-520 doi: 10.1007/s11705-017-1658-7

摘要： The patient receives a pharmaceutical product, not a drug. The pharmaceutical products are formulated with a drug, an active ingredient to produce the maximum therapeutic effect after oral absorption. Therefore, it is the product we must optimize for the patients. In order to assure the safety and efficacy of pharmaceutical products, we need an predictive tool for oral product performance in patients. Currently, we are a surprisingly long way from accomplishing that objective. If the 20th century was the ‘age of the drug’, i.e., the ‘magic bullet’, the 21st century must become the ‘age of the guided missile’, i.e., the delivery system, including the form of the active pharmaceutical ingredient (API) (‘drug’). The physical form of the drug and the delivery system must be optimized to maximize the therapeutic benefits of pharmaceutical products for humans. Oral immediate release (IR) dosage forms cannot be optimal for all drugs or likely even any drugs (APIs). Still, the formulation of pharmaceutical products has to be optimized for patients. But how do we optimize oral delivery of drugs? It is usually through ‘trial and error’, in humans! We need a better way to optimize the oral dosage forms. We have suggested to select different dissolution methodologies for this optimization based on BCS Subclasses. In this article, we present the predicted drug dissolution profile of ketoconazole as a model drug from our laboratory utilizing a gastrointestinal simulator (GIS), which is an adaptation of the ASD system. GIS consists of three chambers representing stomach, duodenum, and jejunum, to create the human gastrointestinal tract-like environment and enable the control the gastric emptying rate. This dissolution system allows the monitoring of the drug dissolution phenomena and the observation of the supersaturation and the precipitation of pharmaceutical products, which is useful information to predict dissolution of pharmaceutical products. This system can provide the actual input needed to accurately predict the input into the systemic circulation required by many of the absorption prediction packages available today.

关键词： GIS     in vivo predictive dissolution     ketoconazole     BCS subclassification     supersaturation    

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Bone regeneration by stem cell and tissue engineering in oral and maxillofacial region

Zhiyuan Zhang

《医学前沿（英文）》 2011年 第5卷 第4期   页码 401-413 doi: 10.1007/s11684-011-0161-7

摘要： Clinical imperatives for the reconstruction of jaw bone defects or resorbed alveolar ridge require new therapies or procedures instead of autologous/allogeneic bone grafts. Regenerative medicine, based on stem cell science and tissue engineering technology, is considered as an ideal alternative strategy for bone regeneration. In this paper, we review the current choices of cell source and strategies on directing the osteogenic differentiation of stem cells. The preclinical animal models for bone regeneration and the key translational points to clinical success in oral and maxillofacial region are also discussed. We propose comprehensive strategies based on stem cell and tissue engineering researches, allowing for clinical application in oral and maxillofacial region.

关键词： bone regeneration     animal models     translational strategies     oral and maxillofacial region    

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Chinese expert consensus on oral drugs for the treatment of mature B-cell lymphomas (2020 edition)

《医学前沿（英文）》 2022年 第16卷 第5期   页码 815-826 doi: 10.1007/s11684-021-0891-0

摘要： Oral drugs such as ibrutinib play an important role in the treatment of mature B-cell lymphoma (BCL) due to their reliable efficacy, manageable safety, high accessibility, and convenience for use. Still, no guidelines or consensus focusing on oral drug therapies for BCL is available. To provide a reference of oral agent-based treatment for mature BCL, a panel of experts from the Lymphocyte Disease Group, Chinese Society of Hematology, Chinese Medical Association conducted an extensive discussion and reached a consensus on oral drugs for Chinese BCL patients on the basis of the current application status of oral drugs in China, combined with the latest authoritative guidelines in the world and current research reports. This consensus reviewed the application of oral drugs in the treatment of BCL and the latest research and provided appropriate recommendations on the use of oral drugs for indolent or aggressive BCL patients. With the deepening of research and the development of standardized clinical applications, oral medications will bring better treatment to BCL patients, enabling more patients to benefit from them.

关键词： B-cell lymphoma     oral drug     targeted therapy     immunotherapy     COVID-19 pandemic    

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Meta-analysis of the risk factors of breast cancer concerning reproductive factors and oral contraceptive

Qiong DAI MD, Bei LIU MD, Yukai DU MM,

《医学前沿（英文）》 2009年 第3卷 第4期   页码 452-458 doi: 10.1007/s11684-009-0080-z

摘要： The authors performed a meta-analysis of case-control studies that addressed whether reproductive factors and oral contraceptive use were associated with breast cancer by searching the MEDLINE, PubMed, Proquest, Embase, ScienceDirect, African Healthline, BMJ Health Intelligence and Chinese Periodical net databases for all English-language and Chinese-language papers published from January 1, 1997 to December 31, 2007. A total of 15 studies calculating pool ORs indicated that menopausal age >50yr [odds ratio (OR), 1.39; 95% confidence interval (CI), 1.22―1.57] and oral contraceptive use (OR, 2.12*, “*”: summary OR was adjusted; 95% CI, 1.24―3.62) were correlated with the increase in breast cancer risk while the summary OR based on number of full-term pregnancies ≥1 (OR, 0.63*; 95% CI, 0.60―0.68) and breast-feeding (OR, 0.76; 95% CI, 0.64―0.90) indicated no association with breast cancer risk. The correlation was statistically significant. Menopausal age >50yr and oral contraceptive use are positively correlated with an increase in breast cancer risk while breast-feeding and number of full-term pregnancies ≥1 are protective factors.

关键词： meta-analysis     breast cancer     risk factors     reproductive factors     oral contraceptive use    

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Biodegradable polymethacrylic acid grafted psyllium for controlled drug delivery systems

Ranvijay KUMAR, Kaushlendra SHARMA

《化学科学与工程前沿（英文）》 2013年 第7卷 第1期   页码 116-122 doi: 10.1007/s11705-013-1310-0

摘要： Polymethacrylic acid (PMA) was synthesized on the backbone of psyllium (Psy) by a microwave assisted method to prepare polymeric grafted materials designated as (Psy- -PMA). Various grades of Psy- -PMA were prepared by changing the degree of grafting from 35%–58% and the materials were then made into tablets. Swelling and biodegradability studies of the tablets were carried out. Acetyl salicylic acid was incorporated in the various Psy- -PMA samples and tablets were prepared to study the in vitro drug release in acidic (pH= 4), neutral (pH= 7), and basic (pH= 9) media. In the acidic medium, the swelling was more than 1300%. In addition, the biodegradable Psy- -PMA had the highest drug release in the acidic medium. This may be attributed to Fickian diffusion since the drug and the medium in which it was released have the same acidic nature.

关键词： psyllium     acetyl salicylic acid     in-vitro drug release     swelling     biodegradation    

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Engineering platelet-mimicking drug delivery vehicles

Quanyin Hu, Hunter N. Bomba, Zhen Gu

《化学科学与工程前沿（英文）》 2017年 第11卷 第4期   页码 624-632 doi: 10.1007/s11705-017-1614-6

摘要： Platelets dynamically participate in various physiological processes, including wound repair, bacterial clearance, immune response, and tumor metastasis. Recreating the specific biological features of platelets by mimicking the structure of the platelet or translocating the platelet membrane to synthetic particles holds great promise in disease treatment. This review highlights recent advancements made in the platelet-mimicking strategies. The future opportunities and translational challenges are also discussed.

关键词： drug delivery     platelets     nanomedicine     bio-inspired     biomimetic    

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Gene delivery into isolated

Nan Zheng, Ziyuan Song, Yang Liu, Lichen Yin, Jianjun Cheng

《化学科学与工程前沿（英文）》 2017年 第11卷 第4期   页码 521-528 doi: 10.1007/s11705-017-1612-8

摘要： The application of gene delivery materials has been mainly focused on mammalian cells while rarely extended to plant engineering. Cationic polymers and lipids have been widely utilized to efficiently deliver DNA and siRNA into mammalian cells. However, their application in plant cells is limited due to the different membrane structures and the presence of plant cell walls. In this study, we developed the cationic, -helical polypeptide that can effectively deliver DNA into both isolated protoplasts and intact leaves. The PPABLG was able to condense DNA to form nanocomplexes, and they exhibited significantly improved transfection efficiencies compared with commercial transfection reagent Lipofectamine 2000 and classical cell penetrating peptides such as poly(L-lysine), HIV-TAT, arginine9, and poly(L-arginine). This study therefore widens the utilities of helical polypeptide as a unique category of gene delivery materials, and may find their promising applications toward plant gene delivery.

关键词： α-helical polypeptide     plant gene delivery     protoplast     intact leaves     transfection    

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Introduction to the special issue of the 2009 International Symposium on Crystal Engineering & Drug Delivery

Zhijian CHEN, Wei LI,

《化学科学与工程前沿（英文）》 2010年 第4卷 第1期   页码 1-1 doi: 10.1007/s11705-009-0306-2

摘要：
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Controlled drug delivery systems: the next 30 years

Yeonhee YUN,Byung Kook LEE,Kinam PARK

《化学科学与工程前沿（英文）》 2014年 第8卷 第3期   页码 276-279 doi: 10.1007/s11705-014-1426-x

摘要： The drug delivery scientists need to reexamine the advances made during the past 60 years, analyze our current abilities, and design the future technologies that will propel us to achieve the next level of drug delivery technologies. History shows that the first generation (1G) of drug delivery research during 1950–1980 was quite productive, while the second generation (2G) technologies developed during 1980–2010 were not as prolific. The ultimate goal of drug delivery research is to develop clinically useful formulations to treat various diseases. Effective drug delivery systems can be developed by overcoming formulation barriers and/or biological barriers. The engineering approach has a limit in solving the problem, if biological difficulties are not clearly identified and understood. The third generation (3G) drug delivery systems will have to focus on understanding the biological barriers so that they can be overcome by engineering manipulation of the drug delivery systems. Advances in the next 30 years will be most accelerated by starting open dialogues without any preconceived ideas on drug delivery technologies. The new generation of drug delivery scientists needs to be aware of the successes and limitations of the existing technologies to design the new technologies for meaningful advances in the future.

关键词： drug delivery     history     formulation barriers     nanotechnology     clinical product    

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Relative expression of PTTG and bFGF in oral squamous cell carcinoma and Tca8113

Yumei DING BM , Lili CHEN MD , Bo CHENG PhD , Handong ZHANG MM ,

《医学前沿（英文）》 2009年 第3卷 第3期   页码 357-362 doi: 10.1007/s11684-009-0046-1

摘要： The purpose of this study was to investigate the expression of pituitary tumor transforming gene (PTTG) and basic fibroblast growth factor (bFGF) in oral squamous cell carcinoma (OSCC) and tongue cancer cell line Tca8113, as well as their effects on each other. We detected PTTG protein and bFGF in OSCC tissues from 56 cases using the streptavidin-biotin peroxidase (S-P) method; additionally, after being treated with different concentrations of anti bFGF or PTTG antibody, PTTG or bFGF expression in Tca8113 was examined by immunocytochemistry. The results were as follows: (1) Positive rates of PTTG protein and bFGF were 78.2% and 67.3% in OSCC, respectively, which were significantly higher than those in normal mucosal tissues (<0.05). PTTG protein was significantly up-regulated in poorly and moderately differentiated tumors compared to well differentiated tumors (<0.05), and there was also a significant difference between tumors with lymph node metastasis and tumors without lymph node metastasis (<0.05). PTTG protein expression was positively correlated with bFGF ( = 0.382, <0.05); (2) PTTG protein emitted strong fluorescence in Tca8113, and it decreased after being treated with anti-bFGF antibody. Anti-PTTG antibody also had an inhibitive effect on bFGF expression. In summary, the overexpression of PTTG protein is closely related with OSCC differentiation and lymph node metastasis. PTTG protein expression conforms to bFGF in OSCC tissues and Tca8113 cells. Detection of both PTTG and bFGF may help to judge the degree of malignancy and prognosis of patients with OSCC.

关键词： carcinoma     squamous cell     pituitary tumor transforming gene (PTTG) protein     basic fibroblast growth factor    

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Bioorthogonal chemistry based on-demand drug delivery system in cancer therapy

《化学科学与工程前沿（英文）》 2023年 第17卷 第4期   页码 483-489 doi: 10.1007/s11705-022-2227-2

摘要： Benefiting from the advantage of taking place in biological environments without interfering with an innate biochemical process, the bioorthogonal reaction that commonly contains the “bond formation” and “bond cleavage” system has been widely used in targeted therapy for a variety of tumors. Herein, several prominent cases based on the bioorthogonal reaction that tailoring the metabolic glycoengineering tactics to modified cells for cancer immunotherapy, and the innovative tactics for reducing the metal ions’ toxic and side effects with microneedle patches will be highlighted. Based on these applications, the complexities, potential pitfalls, and opportunities of bioorthogonal chemistry in future cancer therapy will be evaluated.

关键词： bioorthogonal reaction     cancer therapy     metabolic glycoengineering     bioorthogonal catalytic patch    

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Effect of the new maternity insurance scheme on medical expenditures for caesarean delivery in Wuxi,

null

《医学前沿（英文）》 2016年 第10卷 第4期   页码 473-480 doi: 10.1007/s11684-016-0479-

摘要：

Aiming to control rising medical expenditures and help improve China’s healthcare systems, this study examined whether a cap-based medical insurance scheme with shared financial interest between the insurance and healthcare providers is effective in containing hospitals’ C-section medical expenditures. We used 6547 caesarean delivery case records from a teaching tertiary-level general public hospital located in Wuxi, China (2004–2013), and used the Chow test to investigate the possibility of significant variation in mean medical expenditures for caesarean deliveries pre- and post-reform. We also used paired sample t-tests and linear regression models to compare the mean medical expenditures between insured and uninsured women undergoing caesarean delivery during the post-reform period. After the scheme’s implementation, medical expenditures for caesarean deliveries declined and the medical expenditures of women covered by the scheme were significantly lower than those of uninsured patients. These findings indicated the scheme’s effectiveness in minimizing caesarean delivery expenditures. The cap-based medical insurance scheme with shared financial interest between insurance and healthcare providers would likely steer healthcare providers’ behaviors in a more cost-effective direction.

关键词： maternity insurance scheme     financial incentive     caesarean delivery     medical expenditure     China    

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标题 作者 时间 类型 操作

Overcoming oral insulin delivery barriers: application of cell penetrating peptide and silica-based nanoporous

Huining HE, Junxiao YE, Jianyong SHENG, Jianxin WANG, Yongzhuo HUANG, Guanyi CHEN, Jingkang WANG, Victor C YANG

期刊论文

A Double-Layer Polysaccharide Hydrogel (DPH) for the Enhanced Intestine-Targeted Oral Delivery of Probiotics

Wen-Can Huang,Wenjie Wang,Wei Wang,Yanan Hao,Changhu Xue,Xiangzhao Mao,

期刊论文

Factors related to compliance with oral analgesic treatment of inpatients with chronic pain

null

期刊论文

Oral product input to the GI tract: GIS an oral product performance technology

Gordon L. Amidon, Yasuhiro Tsume

期刊论文

Bone regeneration by stem cell and tissue engineering in oral and maxillofacial region

Zhiyuan Zhang

期刊论文

Chinese expert consensus on oral drugs for the treatment of mature B-cell lymphomas (2020 edition)

期刊论文

Meta-analysis of the risk factors of breast cancer concerning reproductive factors and oral contraceptive

Qiong DAI MD, Bei LIU MD, Yukai DU MM,

期刊论文

Biodegradable polymethacrylic acid grafted psyllium for controlled drug delivery systems

Ranvijay KUMAR, Kaushlendra SHARMA

期刊论文

Engineering platelet-mimicking drug delivery vehicles

Quanyin Hu, Hunter N. Bomba, Zhen Gu

期刊论文

Gene delivery into isolated

Nan Zheng, Ziyuan Song, Yang Liu, Lichen Yin, Jianjun Cheng

期刊论文

Introduction to the special issue of the 2009 International Symposium on Crystal Engineering & Drug Delivery

Zhijian CHEN, Wei LI,

期刊论文

Controlled drug delivery systems: the next 30 years

Yeonhee YUN,Byung Kook LEE,Kinam PARK

期刊论文

Relative expression of PTTG and bFGF in oral squamous cell carcinoma and Tca8113

Yumei DING BM , Lili CHEN MD , Bo CHENG PhD , Handong ZHANG MM ,

期刊论文

Bioorthogonal chemistry based on-demand drug delivery system in cancer therapy

期刊论文

Effect of the new maternity insurance scheme on medical expenditures for caesarean delivery in Wuxi,

null

期刊论文