SBIR Phase I: Lipoleosomes as Carriers for Topical Ibuprofen

这个SBIR第一阶段项目解决了医学方面的关键需求？有选择地将药物输送到需要药物治疗的身体部位的能力。靶向给药通过局部治疗组织，同时减少其他地方的总体暴露和副作用，改善患者的预后。例如，一种面霜或乳液类产品将抗炎药物通过皮肤专门转移到受影响的关节，比服用治疗全身的药片要好。纳米颗粒，特别是脂质体(纳米大小的水球，由包裹在水中的脂肪壁组成)对于靶向药物输送是有用的，因为它们能够穿透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，因为载药量太小，特别是对水不溶性药物。脂质体是一种新型的脂质体，具有更大的载药能力。该项目的目标是用布洛芬制成脂质体，布洛芬是一种水不溶药物，并展示了布洛芬通过皮肤进行局部治疗关节和肌肉的能力。这对于开发一种在治疗关节炎和损伤的同时避免胃部问题的乳液产品将是有价值的。脂质体的产生源于一项非凡的发现？在一定条件下，微乳中存在的扁平脂肪层(脂双层)可以通过水合作用重塑为球形脂质体。由于微乳液脂双层可能含有大量不溶于水的(疏水)化合物(很容易高达65%)，所以产品脂质体也可以。此前，脂质体中的疏水药物含量很少超过5%。鉴于极大的药物容量，新的脂质体被命名为脂微体，表明有机化合物(油)已被插入其中的脂质体。一些微乳脂层重塑形成膜结构，这是科学上的好奇，因为在过去，人们只知道水合作用得到的是填充的乳液滴，而不具有脂质体的重要生物学特性。在本项目中，通过了解前驱体微乳性质和工艺条件的影响，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供应，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，对许多其他药物和皮肤以外的给药途径都有意义。

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.