Arginine-stabilized mPEG-PDLLA (50/50) polymeric micelles of docetaxel by electrostatic mechanism for tumor-targeted delivery

Abstract

Arginine-stabilized, docetaxel-loaded polymeric micelles (AR-DTX-PM) were prepared to enhance the physical stability of micelles and control the degradation of docetaxel (DTX). Amphiphilic diblock copolymers, methoxy-(Polyethylene Glycol)-block-Poly (D, L-lactide) (mPEG-PDLLA) were synthesized and used for the formulation of lyophilized DTX-PM powders. The micelles were found to have diameters of 20–30?nm with narrow polydispersity, and the entrapment efficiency was 90–100%. The accumulative release of AR-DTX-PM was higher than that of glucose-dispersed DTX-PM (Glu-DTX-PM). The results of both physical and chemical stability studies showed that the concentration of arginine required for optimum stability was 2.0?mg/ml. Preliminary investigation of the mechanisms of stabilization by arginine suggested that it is due to the electrostatic interaction as well as hydrogen bonds between DTX and arginine. The acute toxicity studies demonstrated that AR-DTX-PM was better tolerated in beagle dogs than DTX injection. However, the pharmacokinetic studies revealed no significant difference in C_max and AUC of AR-DTX-PM compared to DTX injection. When AR-DTX-PM was administrated at a dose of 30?mg/kg, the antitumor effect was stronger than that of commercial DTX injection at 10?mg/kg, and the increase of administration dose did not cause higher toxicity. The in vivo imaging test showed that the residence time of AR-DTX-PM at tumor sites was longer than its commercial formulation. In a word, it is expected that AR-DTX-PM can reduce systemic toxicity while retaining antitumor efficacy in cancer patients.     

The clinical effects of sodium hyaluronate,polyethylene glycol,and dextran-70 eye drops in relieving dry eye after phacoemulsification

To compare the clinical efficacy of sodium hyaluronate eye drops, polyethylene glycol eye drops, and compound dextran eye drops in the treatment of dry eye after phacoemulsification of cataract.A total of 99 patients with dry eye after cataract phacoemulsification combined with intraocular lens implantation were treated in our hospital. Patients were divided into group A (sodium hyaluronate eye drops), group B (polyethylene glycol eye drops), and group C (dextran-70 eye drops). The clinical effect, tear film breakup time, basic tear secretion, corneal staining score, dry eye symptom score, and the incidence of ocular irritation were assessed.On the 3rd, 15th, 30th, and 60th day after operation, the tear film breakup time, corneal staining score, Schirmer I test, and dry eye symptom score in group A and group B were better than those in group C (P < .05). In addition, there were no significant differences in tear breakdown time, corneal staining score, Schirmer I test, and dry eye symptom score between group A and group B (P > .05). At 3 days to 60 days after operation, the incidence of dry eye in group A (12.12%) and group B (18.18%) was lower than that in group C (39.39%), and the incidence of dry eye in group A was significantly lower than that in group B (P < .05).The effect of sodium hyaluronate eye drops elicited a greater beneficial impact as compared to polyethylene glycol eye drops and dextran-70 eye drops.     

Operative treatments for osteochondral lesions of the talus in adults: A systematic review and meta-analysis

Purpose:This systematic review aimed to identify the available evidence regarding the comparative effectiveness and safety of various operative treatments in adult patients with osteochondral lesions of the talus (OLT).Materials and methods:The PubMed, Embase, ISI Web of Knowledge, and the Cochrane Controlled Trial Register of Controlled Trials were searched from their inception date to September 2019. Two reviewers selected the randomized controlled trials (RCTs) and non-RCTs assessing the comparative effectiveness and safety of various operative treatments for OLT. The meta-analysis was performed using Revman 5.3.Results:Eight studies (1 RCT and 7 non-RCTs) with 375 patients were included in this review. The difference in the American Orthopaedic Foot and Ankle Society (AOFAS) score between the cartilage repair and replacement was not significant. The cartilage regeneration with or without cartilage repair had significant superiority in improving the AOFAS score compared with the cartilage repair. The difference in the magnetic resonance observation of cartilage repair tissue score between the cartilage repair and replacement and between cartilage repair and cartilage repair plus regeneration was significant.Conclusions:Cartilage regeneration and cartilage repair plus regeneration had significant superiority in improving the ankle function and radiological evaluation of OLT, although the trials included did not have high-level evidence. Moreover, which treatment between the 2 was safer could not be addressed in this review as most of the trials did not report the safety outcome. Further studies are needed to define the best surgical option for treating OLT.     

The efficacy of moxibustion and acupuncture therapy for ankylosing spondylitis: A protocol for an overview of systematic reviews and meta-analysis

Background:Ankylosing spondylitis is a complex and progressive autoimmune inflammatory disease with a worldwide prevalence ranging up to 0.9%. Several systematic reviews and meta-analyses of traditional Chinese medicine alternative therapies, such as acupuncture or moxibustion, have demonstrated the effectiveness of moxibustion and acupuncture in the treatment of ankylosing spondylitis. However, there is no relevant literature to comprehensively evaluate the evidence. The purpose of this overview is to synthesize and evaluate the reliability of evidence generated in the systematic review (SR) and meta-analysis of moxibustion and acupuncture as a primary or complementary therapy for patients with ankylosing spondylitis.Methods:PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, Chinese VIP Information, Wanfang Database, and Chinese Biomedical Literature Database were searched for systematic reviews and meta-analysis that review the efficacy of acupuncture or moxibustion as the primary treatment for patients with Ankylosing Spondylitis. The literature published before August 2020 will be selected. Additionally, the relevant SRs and meta-analyses that unpublished or ongoing will be searched in PROSPERO and INPLASY. The methodological guidelines for overviews will be used to review and extract data by 2 reviewers, and their will do it independently. Methodology quality will be analyzed by the assessment of multiple systematic reviews-2and the risk of bias by POBIS. For the included studies, we will adopt the following results as primary evaluation indicators: effective rate, visual analogue scale and bath AS disease activity index. Reviewers will assess the certainty of evidence by Grading of Recommendations Assessment, Development and Evaluation.Results:The results will be published in a peer-reviewed journal.Conclusion:This overview will provide comprehensive evidence of moxibustion and acupuncture for patients with Ankylosing Spondylitis.     

Toujie Quwen granule used with conventional western therapy for coronavirus disease 2019: A protocol for systematic review and meta-analysis

Background:Coronavirus disease 2019 (COVID-19) is an epidemic infectious disease resulted from 2019 novel coronavirus (2019-nCoV). Up till now, COVID-19 has swept globally. Currently, due to many high-profiled benefits, clinical studies on Toujie Quwen granule (TJQW) have been increasing. The aim of the study is to assess the efficacy and safety of TJQW used with conventional western therapy for COVID-19.Methods:Relevant randomized controlled trials (RCTs) were searched in Chinese and English databases, and the search time is January 2020 to May 2021. English databases include PubMed, Embase, Web of Science, and the Cochrane Library. Chinese databases include CNKI, WF, VIP, and CBM. The international clinical trial registration platform and the Chinese clinical trial registration platform of controlled trials will be searched by us from January 2020 to May 2021. According to the inclusion and exclusion criteria, screening literature, extraction data will be conducted by 2 researchers independently. Statistical analysis will be conducted using the RevMan 5.3.5 software. After screening the literature based on the inclusion and exclusion criteria, The Recommendation, Assessment, Development, and Evaluation (GRADE) system will be used to evaluate the quality of each result.Results:This study will provide the evidence for TJQW to be used with conventional western therapy for COVID-19.Conclusion:The efficacy and safety of TJQW used with conventional western therapy for COVID-19 will be assessed.INPLASY registration number:INPLASY202150038