Hybrid lipopolymer vesicle drug delivery and release systems

Hybrid lipopolymer vesicles are membrane vesicles that can be self-assembled on both the micro-and nano-scale.On the nanoscale,they are potential novel smart materials for drug delivery systems that could combine the relative strengths of liposome and polymersome drug delivery systems without their respective weaknesses.However,little is known about their properties and how they could be tailored.Currently,most methods of investigation are limited to the microscale.Here we provide a brief review on hybrid vesicle systems with a specific focus on recent developments demonstrating that nanoscale hybrid vesicles have different properties from their macroscale counterparts.

Factors associated with trigger digit following carpal tunnel release

BACKGROUND Trigger digit is a common disorder of the hand associated with carpal tunnel syndrome.Carpal tunnel release(CTR)surgery may be a risk factor for trigger digit development;however,the association between surgical approach to CTR and postoperative trigger digit is equivocal.AIM To investigate patient risk factors for trigger digit development following either open carpal tunnel release(OCTR)or endoscopic carpal tunnel release(ECTR).METHODS This retrospective chart analysis evaluated 967 CTR procedures from 694 patients for the development of postoperative trigger digit.Patients were stratified according to the technique utilized for their CTR,either open or endoscopic.The development of postoperative trigger digit was evaluated at three time points:within 6 mo following CTR,between 6 mo and 12 mo following CTR,and after 12 mo following CTR.Firth’s penalized likelihood logistic regression was conducted to evaluate sociodemographic and patient comorbidities as potential independent risk factors for trigger digit.Secondary regression models were conducted within each surgical group to reveal any potential interaction effects between surgical approach and patient risk factors for the development of postoperative trigger digit.RESULTS A total of 47 hands developed postoperative trigger digit following 967 CTR procedures(4.9%).In total,64 digits experienced postoperative triggering.The long finger was most commonly affected.There was no significant difference between the open and endoscopic groups for trigger digit development at all three time points following CTR.Furthermore,there were no significant independent risk factors for postoperative trigger digit;however,within group analysis revealed a significant interaction effect between gender and surgical approach(P=0.008).Females were more likely to develop postoperative trigger digit than males after OCTR(OR=3.992),but were less likely to develop postoperative trigger digit than males after ECTR(OR=0.489).CONCLUSION Patient comorbidities do not influence the development of trigger digit following CTR.Markedly,gender differences for postoperative trigger digit may depend on surgical approach to CTR.

Size-transformable nanoparticles with sequentially triggered drug release and enhanced penetration for anticancer therapy

There are several limitations to the application of nanoparticles in the treatment of cancer,including their low drug loading,poor colloidal stability,insufficient tumor penetration,and uncontrolled release of the drug.Herein,gelatin/laponite(LP)/doxorubicin(GLD)nanoparticles are developed by crosslinking LP with gelatin for doxorubicin delivery.GLD shows high doxorubicin encapsulation efficacy(99%)and strong colloidal stability,as seen from the unchanged size over the past 21 days and reduced protein absorption by 48-fold compared with unmodified laponite/doxorubicin nanoparticles.When gelatin from 115 nm GLD reaches the tumor site,matrix metallopeptidase-2(MMP-2)from the tumor environment breaks it down to release smaller 40 nm LP nanoparticles for effective tumor cell endocytosis.As demonstrated by superior penetration in both in vitro three-dimensional(3D)tumor spheroids(138-fold increase compared to the free drug)and in vivo tumor models.The intracellular low pH and MMP-2 further cause doxorubicin release after endocytosis by tumor cells,leading to a higher inhibitory potential against cancer cells.The improved anticancer effectiveness and strong in vivo biocompatibility of GLD have been confirmed using a mouse tumor-bearing model.MMP-2/pH sequentially triggered anticancer drug delivery is made possible by the logical design of tumor-penetrating GLD,offering a useful method for anticancer therapy.

Formation strategies,mechanism of intracellular delivery and potential clinical applications of pH-sensitive liposomes

pH-sensitive liposomes are designed to specifically triggered release the loaded drugs in response to the change of pH in the surrounding serum.So pH-sensitive liposomes can effectively deliver drug or gene fragments into the cytoplasm via the endocytotic pathway.Furthermore,pH-sensitive liposomes can be successfully used in clinical if they enable the encapsulated drugs to be targeted to pathological tissues(such as primary tumors,metastases,local ischemia,inflammation and infection)of the body in which pH is less than the normal physiological value.That’s the reason why a growing amount of literatures described the development and applications of pH-sensitive liposomes to improve the therapeutic index of the encapsulated active ingredients.In this review,the commonly used pH-sensitive molecules for pH-sensitive liposome and the mechanisms of intracellular delivery of pH-sensitive liposomes were addressed.Besides,the potential clinical applications were fully discussed in detail with an expectation to contribute to the clinical research of pH-sensitive liposomes.

Hair follicles as a target structure for nanoparticles

For at least two decades,nanoparticles have been investigated for their capability to deliver topically applied substances through the skin barrier.Based on findings that nanoparticles are highly suitable for penetrating the blood--brain barrier,their use for drug delivery through the skin has become a topic of intense research.In spite of the research efforts by academia and industry,a commercial product permitting the nanoparticle-assisted delivery of topically applied drugs has not yet been developed.However,nanoparticles of approximately 600 nm in diameter have been shown to penetrate fficiently into the hair fllieles where they can be stored for several days.The successful loading of nanoparticles with drugs and their triggered release inside the hair fllile may present an ideal method for localized drug delivery.Depending on the particle size,such a method would permit targeting specific structures in the hair fllicles such a stem ells or immune cells or blood vessels found in the vicinity of the hair follicles.

ROS-responsive thioether-containing hyperbranchede polymer micelles for light-triggered drug releas

As a kind of promising drug carriers,smart polymers have attracted much attention due to the effective and controlled drug release in target cells.Herein,a reactive oxygen species(ROS)-responsive thioether-containing amphiphilic hyperbranched polymer prepared from MTPA and TMPTGE(HBPMT)is synthesized from 3-(methylthio)propylamine(MTPA)and trimethylolpropane triglycidyl ether(TMPTGE)by the amine-epoxy click reaction via A2+B3 onepot approach.Benefiting from its inherent amphiphilic nature,HBPMT can selfassemble into stable micelles in water.Triggered by H_(2)O_(2),these micelles can be dissociated rapidly because hydrophobic thioether segments in their cores are oxidized into hydrophilic sulfoxide or sulfone groups.Additionally,the ROS produced by photosensitizer under light irradiation can also play the same role of H_(2)O_(2).Such HBPMT micelles can be utilized to encapsulate anticancer drug paclitaxel(PTX)and photosensitizer chlorin e6(Ce6)simultaneously for drug delivery and control release.The methyl thiazolyl tetrazolium assay toward MCF-7 tumor cells(a human breast adenocarcinoma cell line)indicates that these micelles encapsulated with PTX and Ce6 exhibit a significant combinational efficacy of cell proliferation inhibition,which means the promising potential for synergistic chemo-photodynamic cancer therapy.Such a novel nanocarrier based on amphiphilic to hydrophilic transition would provide a candidate for controlled drug release and cancer combination therapy.