A pentapeptide enabled AL3810 liposome-based glioma-targeted therapy with immune opsonic effect attenuated

AL3810, a molecular dual inhibitor of the vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR), has earned the permission of phase II clinical trial for tumor treatment by China FDA. As a reversible ATP-competitive inhibitor, AL3810 targets ATP-binding site on intracellular region of VEGFR and FGFR, whereas, AL3810 lacking interplay with extracellular region of receptors rendered deficient blood-brain tumor barrier (BBTB) recognition, poor brain penetration and unsatisfactory anti-glioma efficacy. Integrin

The dilemma and breakthrough of oral administration of insulin / 药学学报

Diabetes is characterized by hyperglycemia, resulting from insulin deficiency or resistance, or both. Insulin plays an irreplaceable role in the treatment of diabetes. Subcutaneous injection is the main route of insulin administration, but usually leads to poor compliance and many side effects. Oral insulin is safer and more convenient, which has always been the Holy Grail for people to explore. After oral administration, insulin is absorbed into the hepatic portal vein and transported to the liver, which can activate the normal physiological functions and reduce the risk of hypoglycemia, insulin resistance, and improve patient compliance. However, the gastrointestinal tract has multiple absorption barriers such as chemical barrier, enzyme barrier, and permeation barrier. Due to the physical and chemical properties of insulin, it is difficult to achieve desired oral bioavailability. This article reviews the recent attempts and progress in the field of oral administration of insulin driven by innovative drug delivery technologies and biomaterials, including structural modification, enzyme inhibitors, absorption enhancers, various nanoparticles, liposomes, microspheres, and even microorganisms. Some clinical researches on oral insulin are also introduced.

Gene therapy and delivery strategies for ocular diseases / 药学学报

Gene therapy has obvious advantages in the treatment of ocular diseases due to the unique structure of the eye. In recent years, there are more and more therapeutic gene-based drugs for ophthalmic application in clinical trials. Most of the delivery vectors are adeno-associated virus and administered via intraocular injection, which has potential risks. Traditional remedies, such as topical instillationor systemic administration, have limited therapeutic effects on the diseases in the posterior segment of the eye, where the chemical drugs are hard to reach. This makes the research of new strategies for gene drug delivery extremely urgent. For better understanding of the latest hot topics of ocular gene therapy, this article is prepared to introduce application of gene therapy to the typical ocular diseases and the corresponding gene-based medicines. The absorption routes for gene delivery into eyes and existing barriers are summarized. Finally, the gene delivery strategies are highlighted. The clinical application of ocular gene therapy will be boosted by overcoming the absorbing barriers and reducing the potential pitfalls.

Liposomes and lipid disks traverse the BBB and BBTB as intact forms as revealed by two-step Förster resonance energy transfer imaging

The blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB) prevent drug and nano-drug delivery systems from entering the brain. However, ligand-mediated nano-drug delivery systems have significantly enhanced the therapeutic treatment of glioma. In this study we investigated the mechanism especially the integrity of liposomes and lipid disks while traversing the BBB and BBTB both and . Fluorophores (DiO, DiI and DiD) were loaded into liposomes and lipid disks to form Förster resonance energy transfer (FRET) nano-drug delivery systems. Using brain capillary endothelial cells as a BBB model, we show that liposomes and disks are present in the cytoplasm as their intact forms and traverse the BBB with a ratio of 0.68‰ and 1.67‰, respectively. Using human umbilical vein endothelial cells as BBTB model, liposomes and disks remained intact and traversed the BBTB with a ratio of 2.31‰ and 8.32‰ at 3 h. imaging and immunohistochemical results revealed that liposomes and disks could traverse the BBB and BBTB as intact forms. In conclusion, these observations explain in part the mechanism by which nano-drug delivery systems increase the therapeutic treatment of glioma.

Value of fast track surgery principles in the perioperative management of liver cancer patients after hepatectomy / 中华消化外科杂志

Objective To investigate the value of fast track surgery (FTS) principles in the perioperative management of liver cancer patients after hepatectomy.Methods Forty patients with primary liver cancer who were admitted to the First People's Hospital of Qinzhou from September 2011 to July 2013 were enrolled in this prospective study.All the patients were randomly divided into the FTS group (20 patients) and the control group (20 patients) according to the random number table.The perioperative management of patients in the FTS group was guided by the FTS principles,patients in the control group were managed with traditional methods.The intraoperative condition,time for portal occlusion,operation time,volume of intraoperative blood loss and blood transfusion,time to drainage tube removal,time to flatus and defecation,duration of postoperative hospital stay,expenses,changes of C-reactive protein on postoperative day 1,3,6,recovery of hepatic function and incidence of postoperative complications.All patients were followed up via phone call and out-patient examination till September 2013.All data were analyzed using the t test or chi-square test.The non-normal distribution paramenters were analyzed using the rank sum test.Results All patients were cured with no perioperative death.The time for postoperative drainage tube removal,time to flatus and defecation,duration of postoperative hospital stay and expenses were (2.3 ± 1.0)days,(2.5 ±0.5)days,(3.1 ±0.7)days,(7.0 ±0.8)days and (3.6 ±0.3) × 104 yuan in the FTS group,and (4.6 ± 0.7) days,(4.3 ± 0.7) days,(4.8 ± 0.4) days,(8.5 ± 0.9) days and (4.1 ± 0.3) ×104 yuan,with significant differences between the 2 groups (t =0.74,0.34,1.70,0.23,0.57,P ＜ 0.05).The levels of C-reactive proteins at postoperative day 1,3,6 were (56 ±7)mg/L,(122 ±7)mg/L and (35 ±7)mg/L in the FTS group,and (198 ± 24) mg/L,(137 ± 5) mg/L and (49 ± 8) mg/L,with significant differences between the 2 groups (F =64.91,P ＜0.05).The levels of prealbumin at postoperative day 1,3,6 were (196 ± 14) mg/L,(243 ± 17) mg/L,(260 ± 10) mg/L in the FTS group,and (198 ± 24) mg/L,(199 ± 16) mg/L and (245 ± 7) mg/L in the control group,with significant differences between the 2 groups (F =22.69,P ＜ 0.05).The levels of alanine transaminase at postoperative day 1,3,6 were (379 ±34)U/L,(166 ± 12)U/L,(49 ± 14)U/L in the FTS group,and (367 ±75)U/L,(210 ±28)U/L,(197 ±22)U/L in the control group,with significant differences between the 2 groups (F =4.51,P ＜ 0.05).One patient was complicated with peritoneal effusion and 1 with thoracic effusion in the FTS group; 4 patients was complicated with peritoneal effusion,3 with thoracic effusion,4 with pulmonary infection and 2 with incisional infection in the control group,with no significant difference in the complication between the 2 groups (x2 =0.78,1.11,4.44,2.11,P ＞ 0.05).All the patients were followed up for 2-24 months,no patients received reoperation or re-admitted to the hospital due to complications.Conclusion The application of FTS principle in the perioperative management of liver cancer patients after hepatectomy is safe and effective,it could alleviate the post-operative stress reaction and accelerate the recovery of liver function and patients' condition.