ResearchPad - expert-review https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[加速肺康复外科,需要精准治疗吗?]]> https://www.researchpad.co/article/5c0528d6d5eed0c48489d102 加速康复外科(enhanced recovery after surgery, ERAS)理念已得到医护的认可,多学科协作是ERAS实践的前提。但现有临床方案实施效果却差异很大,原因何在呢?分析主要原因是统一方案不一定适应于所有手术患者,是否存在“过度医疗”呢?换言之,ERAS是否也需要精准治疗呢?本文主要以肺手术后的加速肺康复(enhanced lung recovery after surgery, ELRAS)为例,分析ERAS精准治疗的必要性及达到的临床效果。一是术前需要肺康复训练的患者人群界定要准确(高危因素的评估标准要精准),肺康复训练为核心,以降低术后并发症为目的;二是术前有明确症状的患者,术前肺康复训练方案也应精准,以控制症状和改善患者生活质量为目的;三是术前无症状及严重相关伴随疾病患者,以优化围手术期流程(精准去掉不必要的操作)为主,以提高患者住院舒适度和缩短平均住院日为目的。总之,加速肺康复外科不是做“加法”而是做“减法”。

]]>
<![CDATA[L-Type amino acid transporter 1 as a target for drug delivery]]> https://www.researchpad.co/article/N0a1405f3-90ba-43a5-86f8-b994dcf292f9

Our growing understanding of membrane transporters and their substrate specificity has opened a new avenue in the field of targeted drug delivery. The L-type amino acid transporter 1 (LAT1) has been one of the most extensively investigated transporters for delivering drugs across biological barriers. The transporter is predominantly expressed in cerebral cortex, blood-brain barrier, blood-retina barrier, testis, placenta, bone marrow and several types of cancer. Its physiological function is to mediate Na+ and pH independent exchange of essential amino acids: leucine, phenylalanine, etc. Several drugs and prodrugs designed as LAT1 substrates have been developed to improve targeted delivery into the brain and cancer cells. Thus, the anti-parkinsonian drug, L-Dopa, the anti-cancer drug, melphalan and the anti-epileptic drug gabapentin, all used in clinical practice, utilize LAT1 to reach their target site. These examples provide supporting evidence for the utility of the LAT1-mediated targeted delivery of the (pro)drug. This review comprehensively summarizes recent advances in LAT1-mediated targeted drug delivery. In addition, the use of LAT1 is critically evaluated and limitations of the approach are discussed.

]]>
<![CDATA[Topical Drug Delivery to the Posterior Segment of the Eye: Addressing the Challenge of Preclinical to Clinical Translation]]> https://www.researchpad.co/article/5c131e8cd5eed0c484992739

Topical delivery of therapeutics to the posterior segment of the eye remains the “holy grail” of ocular drug delivery. As an example, anti–vascular endothelial growth factor biologics, such as ranibizumab, aflibercept, and bevacizumab, are delivered by intravitreal injection to treat neovascular age-related macular degeneration and, although these drugs have revolutionized treatment of the disease, less invasive alternatives to intravitreal injection are desired. Multiple reports in the literature have demonstrated topical delivery of both small and large molecules to the back of the eye in small animal models. Despite this progress, successful translation to larger species, and ultimately humans, has yet to be demonstrated. Selection of animal models with relevant ocular anatomy and physiology, along with appropriate experimental design, is critical to enable more relevant feasibility assessments and increased probability of successful translation.

]]>
<![CDATA[Sheddable Coatings for Long-Circulating Nanoparticles]]> https://www.researchpad.co/article/5b7d6a98463d7e3491c3d6a5

Nanoparticles, such as liposomes, polymeric micelles, lipoplexes and polyplexes are frequently studied as targeted drug carrier systems. The ability of these particles to circulate in the bloodstream for a prolonged period of time is often a prerequisite for successful targeted delivery. To achieve this, hydrophilic ‘stealth’ polymers, such as poly(ethylene glycol) (PEG), are used as coating materials. Such polymers shield the particle surface and thereby reduce opsonization by blood proteins and uptake by macrophages of the mononuclear phagocyte system. Yet, after localizing in the pathological site, nanoparticles should deliver their contents in an efficient manner to achieve a sufficient therapeutic response. The polymer coating, however, may hinder drug release and target cell interaction and can therefore be an obstacle in the realization of the therapeutic response. Attempts have been made to enhance the therapeutic efficacy of sterically stabilized nanoparticles by means of shedding, i.e. a loss of the coating after arrival at the target site. Such an ‘unmasking’ process may facilitate drug release and/or target cell interaction processes. This review presents an overview of the literature regarding different shedding strategies that have been investigated for the preparation of sterically stabilized nanoparticulates. Detach mechanisms and stimuli that have been used are described.

]]>
<![CDATA[In Vivo Methods for the Assessment of Topical Drug Bioavailability]]> https://www.researchpad.co/article/5b7d89a1463d7e7c2c629b73

This paper reviews some current methods for the in vivo assessment of local cutaneous bioavailability in humans after topical drug application. After an introduction discussing the importance of local drug bioavailability assessment and the limitations of model-based predictions, the focus turns to the relevance of experimental studies. The available techniques are then reviewed in detail, with particular emphasis on the tape stripping and microdialysis methodologies. Other less developed techniques, including the skin biopsy, suction blister, follicle removal and confocal Raman spectroscopy techniques are also described.

]]>
<![CDATA[The Need for Restructuring the Disordered Science of Amorphous Drug Formulations]]> https://www.researchpad.co/article/5b41d20c463d7e0d6b4fc57d

The alarming numbers of poorly soluble discovery compounds have centered the efforts towards finding strategies to improve the solubility. One of the attractive approaches to enhance solubility is via amorphization despite the stability issue associated with it. Although the number of amorphous-based research reports has increased tremendously after year 2000, little is known on the current research practice in designing amorphous formulation and how it has changed after the concept of solid dispersion was first introduced decades ago. In this review we try to answer the following questions: What model compounds and excipients have been used in amorphous-based research? How were these two components selected and prepared? What methods have been used to assess the performance of amorphous formulation? What methodology have evolved and/or been standardized since amorphous-based formulation was first introduced and to what extent have we embraced on new methods? Is the extent of research mirrored in the number of marketed amorphous drug products? We have summarized the history and evolution of amorphous formulation and discuss the current status of amorphous formulation-related research practice. We also explore the potential uses of old experimental methods and how they can be used in tandem with computational tools in designing amorphous formulation more efficiently than the traditional trial-and-error approach.

]]>