伤口治疗用载药微针的研究进展

在伤口治疗过程中,因皮肤屏障的限制,药物在角质层积聚使得治疗效率低。微针是治疗伤口的一种新型药物递送系统,可刺穿皮肤的表皮层,将药物送入真皮层,从而发挥促进伤口愈合的作用。该文综述了近几年国内外用于伤口治疗的微针系统,根据微针负载的药物对研究进行分类,并讨论了微针系统在促进伤口愈合方面的优势,总结了微针用于治疗伤口的未来前景和挑战。     

皮肤感染治疗药开发的利弊

皮肤和皮肤结构感染是最常见的细菌感染，但与呼吸道和泌尿道感染相比其发生率较低。因此，与此有关的处方占总抗菌药处方的比例不大，亦即皮肤感染治疗对抗感染药总销售额的贡献较小。然而，皮肤感染也是为数不多的未满足治疗需求在增长的细菌感染领域之一。目前，大多数治疗皮肤感染的产品都不是主要定位于这类疾病，而是用途广泛的广谱抗菌药。     

眼用微针药物递送系统研究进展

由于眼睛特殊的生理结构,眼部疾病(包括眼前段和眼后段)的治疗一直是充满挑战的。传统的给药方式,如局部给药和全身给药,生物利用度低,难以达到治疗效果。临床常用的眼部注射给药,虽可克服生物膜屏障,但一系列严重的不良反应使患者的耐受性差。微针,是一种微创无痛且具有穿透性的给药方式,可将药物递送至眼前段和眼后段,在眼部疾病的应用中受到了广泛的关注。目前,用于眼部药物递送的微针主要有涂布微针、中空微针和可溶微针3类,本文分别概述了3类眼用微针的代表性研究,分析各类微针的特点,为微针在眼部药物递送中的扩大应用提供参考。     

生物可降解微针的研究进展

微针给药是一种新型的经皮给药方式,可在皮肤上创造微米级的药物运输通道,增强皮肤对药物尤其是大分子药物的渗透性,且不会到达神经分布丰富的皮肤深层组织。生物可降解微针是以生物可降解材料为基质制作出的微针,除具有一般微针的优点,其具有的生物可降解特性解决了微针一旦断裂于皮肤内难以处理这一难题。因此生物可降解微针有望成为经皮给药的理想载体。本文对生物可降解微针的特点、制作方法、基质的选择、在经皮给药系统中的应用以及存在的问题等进行了概述。     

微针技术的研究进展

微针以微机电系统(m icroelectro-mechani-cal systems,MEMS)技术为基础,在近年来发展迅速。本文主要介绍微针的制备方法,插入皮肤的机制,微针给药的特点以及微针的应用,详细介绍了微针在经皮给药中的应用。由于微针给药可以避免胃肠道对药物的降解作用和肝脏的首过效应等口服给药的缺点,并可消除注射给药时引起的疼痛,随着其发展不断完善,微针给药将会有广阔的应用前景。     

经皮载药微针的现代研究进展

本研究以“微针”和“microneedles”为关键词,检索2017—2022年中国知网(CNKI)和PubMed数据库中的相关文献,从微针载体的结构研究、制备方法、药效学研究及临床应用研究四方面进行综述。在两大数据库中共检索得到有效文献1 040篇。其中,微针结构的研究包含固体微针、涂层微针、可溶性微针、水凝胶微针及中空微针;微针的制备方法包括微模塑法、拉延光刻法及3D打印法;微针载体的药效学研究涵盖对皮肤类、代谢类、免疫类及眼部疾病的治疗;微针的临床应用研究包括疫苗、射频疗法及生物诊断研究等。结合药物制剂新技术,开发新的经皮微针给药系统是微针未来研究的主要方向,本研究为进一步开发微针透皮给药制剂提供参考,以期为微针相关研究提供参考和借鉴。     

可分离微针研究进展

可分离微针属于可溶性微针的一种,应用于皮肤后其针尖与背衬可快速分离,有效减少了微针的佩戴时间以及提高了给药效率,是一种新型透皮给药系统,因此近年来成为研究热点。目前国内外已经开发出多种形式的可分离微针,体内外研究证实可分离微针具有广阔的应用前景。本文概述了当前可分离微针的特点与分类,以期对后续可分离微针的开发与应用提供参考。     

金因肽局部治疗糖尿病皮肤感染的临床观察

皮肤感染是糖尿病的常见并发症之一.患者由于血糖高及周围神经血管病变,皮肤黏膜容易发生感染,且损伤后不易自愈,严重影响患者的日常生活.因此,在全身降糖抗炎治疗的同时,如何进行皮肤糜烂或溃疡的快速愈合,是医生与患者共同关注的问题.金因肽的成分是重组人表皮生长因子(Recombinant human epidermal growth factor,rhEGF,)具有加快上皮修复的功能,我们应用金因肽联合内科全身治疗糖尿病皮肤感染患者收到了令人满意的效果,现报告如下.     

Dalbavancin for the treatment of acute bacterial skin and skin structure infections

Introduction: Acute bacterial skin and skin structure infections (ABSSSI) have increased in incidence and severity. The involvement of resistant organisms, particularly methicillin-resistant Staphylococcus aureus, presents additional challenges. The lipoglycopeptide dalbavancin has a prolonged half-life, high protein binding, and excellent tissue levels which led to its development as a once-weekly treatment for ABSSSI. In the pivotal DISCOVER 1 and DISCOVER 2 trials, dalbavancin proved non-inferior to vancomycin followed by linezolid when used sequentially for ABSSSI, forming the basis for its recent approval in the US and Europe for ABSSSI.

Areas covered: A literature search of published pharmacologic and clinical data was conducted to review the chemistry, pharmacodynamics, and pharmacokinetics of dalbavancin. We also discuss its development process, highlighting efficacy and safety data from pertinent clinical trials and the role it could play in the current clinical landscape.

Expert opinion: DISCOVER 1 and DISCOVER 2 demonstrated dalbavancin’s non-inferiority to vancomycin followed by linezolid for ABSSSI and confirmed its safety and tolerability. They were among the first trials to use new, early primary efficacy endpoints, and dalbavancin was among the first agents designated a Qualified Infectious Disease Product for expedited review. Dalbavancin may prove to be a valuable option for ABSSSI patients in whom conventional therapy is limited.     

Site-specific drug delivery in the skin for the localized treatment of skin diseases

ABSTRACT

Introduction: Due to the well-organized structure and barrier function of the skin, it is generally difficult for drugs applied directly on the surface of skin to reach their expected site of action. Accordingly, site-specific drug delivery in the skin has been increasingly explored to facilitate the treatment of skin diseases and reduce the systemic toxicity.

Area covered: An overview of the generally used sites for drug delivery in the skin is herein presented. Different strategies including particle-based carriers, physical technologies, and chemical approaches are discussed with regards to their potential application in site-specific drug delivery in the skin.

Expert opinion: Particle-based carriers are of particular significance for the enhancement of drug delivery in the skin. Although no recommendation can be made regarding which type of carriers can provide better skin penetration, the lipid-based colloidal systems appear to be favored due to their compatibility. In addition, the physical technologies provide unique advantages in delivering hydrophilic macromolecules for the skin immunization. As a new class of permeation enhancers, skin penetrating peptides are gaining more attention in drug delivery to skin cells. For the design of robust site-specific drug delivery systems, the impacts of diseased state and drug properties should not be disregarded.     

Localized delivery of a lipophilic proteasome inhibitor into human skin for treatment of psoriasis

Purpose: Pentaerythritol tetrakis (3,5-di-tert-butyl-4-hydroxyhydrocinnamate) (PTTC) is a cinnamate tetraester with proteasome inhibitor activity, which may be used as a topical treatment in psoriasis, but has a computed log?P of 23. The objective of this in vitro study was to determine the intradermal delivery, skin irritation and potential efficacy of PTTC in treating psoriasis.

Methods: Solubility studies were performed to find a suitable vehicle for PTTC. Permeation studies were performed with microneedle-treated skin. A cell culture irritation test was dosed with a positive control, negative control and PTTC. An MTT assay was performed to evaluate cell viability and irritancy. Psoriatic cell culture was also dosed with PTTC and IL-6 levels were determined by ELISA.

Results: Solubility was greatest in dimethyl sulfoxide and ethyl pyruvate, with dimethyl sulfoxide delivering a greater amount (2343.41?±?384.26?µg) into stratum corneum. PTTC alone as well as topical PTTC emulsion formulation were found to be non-irritant with cell viability of 69.0?±?5.64% and 74.6?±?5.03%, respectively. Treatment with neat PTTC slightly reduced IL-6 levels and PTTC emulsion significantly reduced IL-6 levels to 92.53?±?12.74?pg/ml compared to basal levels (141.69?±?8.41?pg/ml).

Conclusion: PTTC can be delivered intradermally to potentially treat psoriasis.     

Clinical and pharmacokinetic drug evaluation of delafloxacin for the treatment of acute bacterial skin and skin structure infections

Introduction: In the era of multi-drug resistant pathogens, the adequate treatment of skin and skin structure infections remains a challenge for clinicians. Delafloxacin, with its broad spectrum against Gram-positive, Gram-negative and anaerobic organisms, represents a new therapeutic option in this setting, especially when coverage of methicillin-resistant Staphylococcus aureus is required in the empirical or targeted approach.

Areas covered: In this drug evaluation, the Authors have reviewed the pharmacokinetic and pharmacodynamic characteristics of delafloxacin. In addition, recent data on clinical efficacy and safety from clinical trials have been included.

Expert opinion: Delafloxacin represents an attractive therapeutic option due to a broad antimicrobial and favorable pharmacokinetic and pharmacodynamic profile. Several in vitro studies have demonstrated the low potential for resistance selection if used in empirical regimens. Delafloxacin is a promising candidate for the treatment of Gram-positive infections, especially if co-infection with other pathogens is suspected. This is because of the very low MIC of the agent for Gram-positive (including MRSA) and anaerobic bacteria and because of the wide spectrum of activity against Gram-negative organisms. For these interesting microbiological and PK/PD characteristics we expect future uses of this drug in other indications such as diabetic foot infection, osteomyelitis, prosthetic joint infections, abdominal infections and central nervous system infections.     

Clinical safety and tolerability of tedizolid phosphate in the treatment of acute bacterial skin and skin structure infections

Background: We evaluated safety and tolerability of tedizolid phosphate at the 200-mg once-daily dose approved for 6-day treatment of skin and skin-structure infections.

Research design and methods: Clinical adverse event (AE) and laboratory data were pooled across completed clinical studies (13 phase 1, two phase 2, and two phase 3), for all participants who received ≥1 dose of tedizolid 200 mg, linezolid 600 mg (phase 3 only), or placebo (phase 1 only).

Results: 1280 participants received tedizolid (phase 1: n = 355; phase 2/3: n = 925). In total, 13% received >6 doses of tedizolid (range: 7–21); in phase 2/3, 94% of participants received ≥5 doses (range: 5–10). Drug-related AEs occurred in 27% of participants (most commonly gastrointestinal reactions in 13% of participants and headache in 4%). Most AEs were mild-moderate in severity; <1% of participants discontinued treatment due to AEs. Tedizolid and linezolid had similar frequency, severity, and types of drug-related AEs. Tolerability in clinically important subpopulations (obese, n = 346; elderly, n = 99; renal impairment, n = 40; hepatic disease/impairment, n = 294) appeared comparable to the overall population.

Conclusions: Tedizolid, given orally or intravenously at 200 mg, has a favorable safety profile. Clinical trial and postmarketing experience with treatment ≥7 days is limited.     

Oritavancin for acute bacterial skin and skin structure infections

Introduction: Inpatient treatment of acute bacterial skin and skin structure infections (ABSSSIs) exerts a significant economic burden on the healthcare system. Oritavancin is a concentration-dependent, rapid bactericidal agent approved for the treatment of ABSSSIs. Its prolonged half-life with one-time intravenous (i.v.) dosing offers a potential solution to this burden. In addition, oritavancin represents an alternative therapy for Streptococci and multidrug-resistant Gram-positive bacteria including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. Animal models have also shown promising results with oritavancin for other disease states including those that require long courses of i.v. therapy.

Areas covered: This review covers oritavancin’s basic chemistry, spectrum of activity, pharmacodynamics/pharmacokinetics and efficacy in clinical trials, and provides expert opinion on future directions. To compose this review, a search of PubMed was performed, and articles written in the English language were selected based on full text availability.

Expert opinion: If oritavancin is proven to be a cost-effective strategy for outpatient treatment and prevents complications of prolonged i.v. therapy, it will be sought as an alternative antibiotic therapy for ABSSSIs. In addition, further clinical data demonstrating efficacy in Gram-positive infections requiring prolonged therapy such as endocarditis and osteomyelitis could support oritavancin’s success in the current market.     

微针技术在经皮给药中的应用

微针是经皮给药的物理促渗方法之一,有着很好的市场前景。本文介绍微针的透皮促渗机制、促进药物经皮渗透的因素、复合技术以及微针在大分子经皮促渗中的应用。     

Dissolving microneedles for enhanced local delivery of capsaicin to rat skin tissue

Capsaicin-loaded dissolving microneedles (DMNs) were prepared to investigate the analgesic effect of capsaicin on the skin. The dimensions of each microneedle (MN) were as follows: diameter of the basement, 17?mm; length, 500?μm; and width, 300?μm. The average capsaicin content in the DMNs loaded with a low and high dose of capsaicin was 8.8?±?0.5?mg and 12.5?±?0.4?mg. Almost all the capsaicin, 99.3?±?4.1% and 99.7?±?2.2% for low-dose and high-dose DMNs were released within 20?min. High amounts of capsaicin were recovered with 102.8?±?0.1% of capsaicin after storage at 23?°C for 90 days. The pharmacological activity of capsaicin DMNs was compared to that of capsaicin cream as a positive control, by measuring the idiospasm of depilated rat skin. The time required to achieve 50% idiospasm suppression was 26.3?±?1.9?min and 53.0?±?2.3?min for low-dose and high-dose DMNs. A pharmacokinetic study showed high tissue capsaicin levels of 660.2?±?120.6 and 1805.3?±?218.1?μg/g wet weight for low-dose and high-dose DMNs at 5?min after administration. The results suggest that DMNs could exert a rapid local analgesic action on the skin.