SBIR Phase I: Lipoleosomes as Carriers for Topical Ibuprofen

SBIR 第一阶段：脂质体作为外用布洛芬的载体

• 批准号: 1647292
• 负责人: Eric Morrison
• 金额: $ 22.5万
• 依托单位: Dynation L. L. C.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-15 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1647292&HistoricalAwards=false
• 关键词: SBIR; Phase; Lipoleosomes; Carriers; Topical

This SBIR Phase I project addresses a critical need in medicine ? the ability to deliver drugs selectively to parts of the body that need medication. Targeted drug delivery improves patient outcomes by treating tissues locally while reducing overall exposure and side effects elsewhere. For example, a cream or lotion type product which moves anti-inflammatory drugs through skin specifically to an affected joint is better than taking a pill which medicates the entire body. Nanoparticles, especially liposomes (nanometer size water balloons consisting of a fatty wall surrounding an aqueous interior) are useful for targeted drug delivery because of their ability to move through biological barriers including skin. Unfortunately, use of liposomes is limited because the drug carrying capacity is too small, especially for water insoluble drugs. Lipoleosomes are a new type of liposome with a much greater carrying capacity for drugs. The objective of this project is to make lipoleosomes with ibuprofen, a water-insoluble drug and demonstrate the ability to move ibuprofen through skin for localized treatment of joints and muscles. This will be valuable for developing a lotion product to treat arthritis and injuries while avoiding stomach problems.The creation of lipoleosomes resulted from a remarkable discovery ? that under certain conditions, flat fatty layers (lipid bilayers) existing in microemulsions can be reshaped by hydration into spherical liposome form. Because microemulsion lipid bilayers can contain large amounts of water-insoluble (hydrophobic) compounds (easily up to 65%), so can the product liposomes. Previously, hydrophobic drug content of liposomes rarely exceeded 5%. In light of the extraordinarily greater drug capacity, the new liposomes were named lipoleosomes, indicating a liposome into which organic compounds (oleo) have been inserted. It is a scientific curiosity that some microemulsion lipid layers reshape to give membrane structures because in the past, hydration had only been known to give filled emulsion droplets which do not have the important biological features of liposomes. In this project, the quality and yield of lipoleosomes and their biological characteristics will be improved by understanding the influence of precursor microemulsion properties and processing conditions. This will result in the availability of new, biologically effective lipoleosomal ibuprofen compositions and methods of synthesis, plus physical and biometric data that supports submission of a new drug application for a topical ibuprofen lotion or cream. Establishing lipoleosomes as a new type of nanoparticle has implications for many other drugs and for routes of administration other than dermal.

这个 SBIR 第一阶段项目解决了医学上的关键需求？将药物选择性地输送到需要药物的身体部位的能力。 靶向药物输送通过局部治疗组织来改善患者的治疗效果，同时减少其他地方的总体暴露和副作用。例如，将抗炎药物通过皮肤输送到受影响的关节的霜剂或乳液类产品比服用治疗全身的药丸更好。纳米颗粒，特别是脂质体（由围绕水性内部的脂肪壁组成的纳米尺寸的水球）可用于靶向药物递送，因为它们能够穿过包括皮肤在内的生物屏障。不幸的是，脂质体的使用受到限制，因为药物承载能力太小，特别是对于水不溶性药物。 脂质体是一种新型脂质体，具有更大的药物承载能力。 该项目的目标是用布洛芬（一种水不溶性药物）制造脂质体，并展示布洛芬通过皮肤移动以对关节和肌肉进行局部治疗的能力。这对于开发治疗关节炎和损伤同时避免胃部问题的乳液产品非常有价值。脂质体的产生源于一项非凡的发现？在一定条件下，微乳液中存在的扁平脂肪层（脂质双层）可以通过水合重塑为球形脂质体形式。由于微乳液脂质双层可以含有大量的水不溶性（疏水性）化合物（很容易高达 65%），因此脂质体产品也可以含有大量的水不溶性（疏水性）化合物。此前，脂质体的疏水性药物含量很少超过5%。鉴于药物容量非常大，新的脂质体被命名为脂质体，表示其中插入了有机化合物（oleo）的脂质体。 科学上的好奇心在于，一些微乳液脂质层重塑以形成膜结构，因为在过去，人们只知道水合作用会产生填充的乳液液滴，而这种乳液液滴不具有脂质体的重要生物学特征。在该项目中，通过了解前体微乳液性质和加工条件的影响，将提高脂质体的质量和产量及其生物学特性。这将导致新的、生物有效的脂质体布洛芬组合物和合成方法的可用性，以及支持提交局部布洛芬洗剂或乳膏的新药申请的物理和生物测定数据。将脂质体建立为一种新型纳米颗粒对许多其他药物和除皮肤以外的给药途径具有影响。