SBIR Phase I: Lipoleosomes as Carriers for Topical Ibuprofen

这个SBIR第一阶段项目解决了医学上的一个关键需求？选择性地将药物输送到需要药物的身体部位的能力。 靶向药物递送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来改善患者的结果。例如，将抗炎药物通过皮肤专门移动到受影响的关节的霜或乳液类型的产品比服用整个身体的药丸更好。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气球）可用于靶向药物递送，因为它们能够移动通过包括皮肤的生物屏障。不幸的是，脂质体的使用受到限制，因为药物携带能力太小，特别是对于水不溶性药物。 脂质体是一种新型的脂质体，具有更大的载药能力。 该项目的目的是用布洛芬（一种水不溶性药物）制造脂质体，并证明布洛芬通过皮肤进行关节和肌肉局部治疗的能力。这将是有价值的发展洗剂产品，以治疗关节炎和伤害，同时避免胃病。在一定条件下，存在于微乳液中的扁平脂肪层（脂质双层）可以通过水合作用重新成形为球形脂质体形式。由于微乳液脂质双层可含有大量的水不溶性（疏水性）化合物（很容易高达65%），因此产品脂质体也是如此。以前，脂质体的疏水性药物含量很少超过5%。鉴于这种新的脂质体具有非常大的药物容量，因此将其命名为脂质体，表明其中插入了有机化合物（油）的脂质体。 一些微乳液脂质层重塑以产生膜结构是科学上的好奇心，因为在过去，仅已知水合作用产生不具有脂质体的重要生物学特征的填充的乳液液滴。在本项目中，将通过了解前体微乳液性质和加工条件的影响来提高脂质体的质量和产量及其生物学特性。这将导致新的、生物学上有效的脂质体布洛芬组合物和合成方法的可用性，加上支持提交用于局部布洛芬洗剂或乳膏的新药申请的物理和生物计量数据。建立脂质体作为一种新型的纳米颗粒对许多其他药物和皮肤以外的给药途径有影响。

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.