Smart Lidocaine Gels for Pain Management

描述(由申请人提供)：这项第一阶段的提案旨在开发一种独特的纳米结构智能利多卡因凝胶，用于特定部位的疼痛治疗。设计和测试这种凝胶系统的假设是基于最近的两项发现。(1)含有麻醉药利多卡因和以Pluronic为基础的嵌段共聚物(聚环氧乙烷-b-聚环氧丙烷-b-聚环氧乙烷)混合物的药物智能凝胶，可以通过共聚物的组成和浓度进行微调，以在体温附近具有热可逆凝胶行为。这些特性将使利多卡因分子能够持续和受控释放，并可促进现场部署途径(例如，低压喷洒、注射或局部涂层)。(2)基于聚电解质复合体(例如，壳聚糖和海藻酸盐的混合物)形成的微观生物可吸收药物颗粒(微米和亚微米尺寸)的动态形成可以提供长达数十天的利多卡因持续释放。为了验证上述假设，提出了三个具体目标，以验证该方法的科学价值和技术可行性。具体目标1：表征和优化利多卡因-Pluronic智能凝胶和含有利多卡因的聚电解质复合微粒的治疗混合物，这些微粒具有持续释放利多卡因的能力(从几天到几周甚至几个月)。具体目标2：体外评估利多卡因-Pluronic智能凝胶、含有利多卡因的聚电解质复合颗粒和含有这种复杂颗粒的智能凝胶的混合物的治疗效果。具体目的3：采用热板法和甩尾法两种大鼠模型测定利多卡因智能凝胶的体内相对有效性。所提出的系统的优势在于其通过在损伤部位控制和持续释放局部麻醉剂来管理疼痛的能力。慢性疼痛的持续性可能会影响个人生活的许多不同方面，从生理变化到社会和经济变化。这项提议旨在开发一种独特的用于止痛的智能利多卡因凝胶。所提出的系统的优势在于其通过在损伤部位控制和持续释放局部麻醉剂来管理疼痛的能力。

DESCRIPTION (provided by applicant): This Phase I proposal aims to develop a unique class of nanostructured smart lidocaine gels for site-specific pain management. The hypothesis for the design and testing of this gel system is based on two recent findings. (1) Medicated smart gels, containing lidocaine (an anesthetic drug) and mixtures of pluronic-based block copolymers (poly (ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide)) in water, can be fine-tuned by copolymer composition and concentration to possess thermo reversible gelation behavior near the body temperature. Such characteristics will enable the sustained and controlled release of lidocaine molecules and can facilitate site deployment pathways (e.g. low pressure spraying, injection or topical coating). (2) The dynamic formation of microscopic bioabsorbable medicated particles (micron and submicron sizes) based on polyelectrolyte complex formation (e.g., mixtures based on chitosan and alginate) can provide a sustained release of lidocaine to tens of days. To test the above hypothesis, three specific aims have been proposed to verify the scientific merits and technical feasibility of the approach. Specific Aim 1: Characterize and optimize therapeutic mixtures of lidocaine-pluronic smart gels and lidocaine containing polyelectrolyte complex particles with sustained lidocaine release capability (from days to weeks or perhaps even months). Specific Aim 2: In vitro assessments of the therapeutic efficacies of mixtures of lidocaine-pluronic smart gels, lidocaine-containing polyelectrolyte complex particles, and smart gels containing such complex particles. Specific Aim 3: Determination of the relative in vivo efficacies of lidocaine-containing smart gels by using two rat models based on the hot-plate test and the tail-flick test. The strength of the proposed system is its ability to manage pain through controlled and sustained release of local anesthetics at the injury site. The persistence of chronic pain can affect many different aspects of personal life, ranging from the physiological to societal and financial changes. This proposal aims to develop a unique class of smart lidocaine gels for pain management. The strength of the proposed system is its ability to manage pain through controlled and sustained release of local anesthetics at the injury site.