Layer-by-layer nanocarriers for highly efficient solubilization of insoluble drug

层层纳米载体可高效溶解不溶性药物

基本信息

  • 批准号:
    8204760
  • 负责人:
  • 金额:
    $ 32.5万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-01-11 至 2013-12-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): By combining the recent developments in engineering of multifunctional pharmaceutical nanocarriers and in preparing novel types of polymeric coatings using the layer-by-layer (LbL) technology, we expect to obtain new dosage forms of poorly soluble drugs and meet the unmet need for stable nanocolloids of such drugs suitable for parental administration. There exist serious problems with currently used micellar carriers for poorly soluble drugs: (a) low loading efficacy of the drug (usually below 5% wt); (b) impossibility to apply the same protocol for different drugs; (c) difficulties in controlling the drug release rate; (d) scaling up the technology; (e) insufficient stability. On the other hand, there exists an approach to assemble polyelectrolyte multilayer shells on various particles through the LbL process based on an alternate adsorption of oppositely charged polyelectrolytes. We plan LbL coatings to make stable aqueous colloids of poorly soluble drugs with high stability, controllable release rate, and very high content (up to 90% wt) of the active drug. For this, aqueous suspensions of poorly soluble drugs with micron range particles are subjected to ultrasonication to bring their size to the nano level, and stabilized drug nanoparticles in solution are formed by applying the LbL coating. We hypothesize that the formation of LbL shell around drug nanoparticles will result in stable drug preparations with high content of an active drug. By varying the charge density on polymers and/or the number of coating cycles, particles with a different surface charge and different composition of the coat can be prepared to control drug release rate. The use of a reactive polymer to form the "outer" surface layer will allow for the attachment of specific ligands or reporter groups and other moieties of interest to drug nanoparticles. The proposal pursues the following specific aims: (1) To prepare stable nanocolloids of poorly soluble drugs - paclitaxel (PCT), and camptothecin (CPT) - with a size of 100-to-200 nm, drug content of above 75% wt, and controllable drug release rate by using the LbL technology; (2) To prepare drug LbL nanocolloids with attached polyethylene glycol (for increased longevity), cancer-specific monoclonal antibody 2C5 or TAT peptide (TATp), for cancer targeting or intracellular penetration; (3) To investigate the properties, cytoxicity, interaction with cells, and cellular uptake and intracellular distribution of non-targeted and targeted LbL nanocolloids of PCT, and CPT in cancer cells in vitro; (4) To investigate the properties of non-targeted and targeted LbL drug nanocolloids in vivo in mice with experimental tumors; and (5) To prepare TATp-modified LbL nanocolloids of PCT, and CPT and study the effect of TATp-mediated intracellular delivery of drug nanocolloids on drug efficiency both in vitro and in vivo. This proposal will develop a novel platform for making stable targeted and non-targeted nanocolloids of poorly soluble drugs with high drug content and enhanced drug bioavailability. PUBLIC HEALTH RELEVANCE: We plan to obtain new dosage forms of poorly soluble drugs suitable for parenteral administration by applying the layer-by-layer (LbL) technology by assembling polyelectrolyte multilayer shells on various particles through the process of an alternate adsorption of oppositely charged polyelectrolytes. This will result in stable aqueous colloids of poorly soluble drugs with high stability, controllable release rate, and very high content (up to 90% wt) of the active drug. By varying the charge density on polymers and/or the number of coating cycles, particles with a controlled surface charge and different composition of the coat can be prepared to control drug release rate. The use of a reactive polymer to form the "outer" surface layer will allow for the attachment of specific ligands or reporter groups and other moieties of interest to drug nanoparticles. The approach will be applied to several poorly soluble anticancer drugs, and the nanocolloids obtained will be additionally modified by various ligands to make them long-circulating, targeted, and capable of intracellular penetration.
描述(由申请人提供):通过结合多功能药物纳米载体工程和使用逐层(LbL)技术制备新型聚合物涂层的最新发展,我们期望获得难溶性药物的新剂型,并满足对适用于胃肠外给药的此类药物的稳定纳米胶体的未满足需求。 目前使用的用于难溶性药物的胶束载体存在严重的问题:(a)药物的低负载效率(通常低于5%wt);(B)不可能对不同的药物应用相同的方案;(c)难以控制药物释放速率;(d)按比例放大技术;(e)稳定性不足。另一方面,存在一种通过基于带相反电荷的聚电解质的交替吸附的LbL过程在各种颗粒上组装多层壳的方法。我们计划LbL涂层,使稳定的水胶体的难溶性药物具有高稳定性,可控的释放速率,和非常高的含量(高达90%wt)的活性药物。为此,将具有微米范围颗粒的难溶性药物的水性悬浮液进行超声处理以使其尺寸达到纳米水平,并通过施加LbL涂层形成溶液中的稳定药物纳米颗粒。 我们假设在药物纳米颗粒周围形成LbL壳将导致具有高含量活性药物的稳定药物制剂。通过改变聚合物上的电荷密度和/或包衣循环次数,可以制备具有不同表面电荷和不同包衣组成的颗粒,以控制药物释放速率。使用反应性聚合物形成“外”表面层将允许特定配体或报告基团和其他感兴趣的部分连接到药物纳米颗粒。 本发明的具体目标是:(1)利用LbL技术制备难溶性药物紫杉醇(PCT)和喜树碱(CPT)的稳定纳米胶体,其粒径为100-200 nm,药物含量大于75%wt,药物释放速率可控;(2)制备了聚乙二醇修饰的药物LbL纳米胶体(用于延长寿命)、癌症特异性单克隆抗体2C 5或达特肽(TATp),用于癌症靶向或细胞内渗透;(3)研究PCT和CPT的非靶向和靶向LbL纳米胶体的性质、细胞毒性、与细胞的相互作用以及在体外癌细胞中的细胞摄取和细胞内分布;(4)研究非靶向和靶向LbL药物纳米胶体在实验性肿瘤小鼠体内的性质;(5)制备三磷酸腺苷(TATP)修饰的PCT和CPT纳米胶体LbL,并研究TATP介导的纳米胶体细胞内给药对体内外药物效率的影响。 该提案将开发一种新的平台,用于制备具有高药物含量和增强药物生物利用度的难溶性药物的稳定靶向和非靶向纳米胶体。 公共卫生关系:我们计划通过应用逐层(LbL)技术,通过交替吸附带相反电荷的聚电解质的过程,在各种颗粒上组装多层壳,从而获得适用于胃肠外给药的难溶性药物的新剂型。这将产生具有高稳定性、可控释放速率和非常高的活性药物含量(高达90%wt)的难溶性药物的稳定水性胶体。通过改变聚合物上的电荷密度和/或包衣循环次数,可以制备具有受控表面电荷和不同包衣组成的颗粒,以控制药物释放速率。使用反应性聚合物形成“外”表面层将允许特定配体或报告基团和其他感兴趣的部分连接到药物纳米颗粒。该方法将应用于几种难溶性抗癌药物,获得的纳米胶体将通过各种配体进行额外修饰,使其具有长循环、靶向和细胞内渗透能力。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Vladimir P Torchilin其他文献

Vladimir P Torchilin的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Vladimir P Torchilin', 18)}}的其他基金

Lipid-dendrimer micellar nanocarriers for siRNA/drug co-delivery in MDR cancer
用于 MDR 癌症中 siRNA/药物共递送的脂质树枝状聚合物胶束纳米载体
  • 批准号:
    9005996
  • 财政年份:
    2015
  • 资助金额:
    $ 32.5万
  • 项目类别:
Multifunctional matrix metalloprotease-2-sensitive anti-cancer nanopreparations
多功能基质金属蛋白酶2敏感抗癌纳米制剂
  • 批准号:
    8701689
  • 财政年份:
    2014
  • 资助金额:
    $ 32.5万
  • 项目类别:
Multifunctional matrix metalloprotease-2-sensitive anti-cancer nanopreparations
多功能基质金属蛋白酶2敏感抗癌纳米制剂
  • 批准号:
    8833261
  • 财政年份:
    2014
  • 资助金额:
    $ 32.5万
  • 项目类别:
Layer-by-layer nanocarriers for highly efficient solubilization of insoluble drug
层层纳米载体可高效溶解不溶性药物
  • 批准号:
    7785335
  • 财政年份:
    2010
  • 资助金额:
    $ 32.5万
  • 项目类别:
Center for Translational Cancer Nanomedicine
转化癌症纳米医学中心
  • 批准号:
    8327154
  • 财政年份:
    2010
  • 资助金额:
    $ 32.5万
  • 项目类别:
Center for Translational Cancer Nanomedicine
转化癌症纳米医学中心
  • 批准号:
    8134375
  • 财政年份:
    2010
  • 资助金额:
    $ 32.5万
  • 项目类别:
Center for Translational Cancer Nanomedicine
转化癌症纳米医学中心
  • 批准号:
    7976256
  • 财政年份:
    2010
  • 资助金额:
    $ 32.5万
  • 项目类别:
Combination Anticancer Nanopreparations of Novel Proapoptotic Drug and siRNA
新型促凋亡药物与 siRNA 联合抗癌纳米制剂
  • 批准号:
    7984269
  • 财政年份:
    2010
  • 资助金额:
    $ 32.5万
  • 项目类别:
Layer-by-layer nanocarriers for highly efficient solubilization of insoluble drug
层层纳米载体可高效溶解不溶性药物
  • 批准号:
    8012286
  • 财政年份:
    2010
  • 资助金额:
    $ 32.5万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    7984282
  • 财政年份:
    2010
  • 资助金额:
    $ 32.5万
  • 项目类别:

相似海外基金

Étude des interactions de sorption et de séquestration de polluants sur des alginates
海藻酸盐污染物吸附与封存相互作用研究
  • 批准号:
    571945-2022
  • 财政年份:
    2022
  • 资助金额:
    $ 32.5万
  • 项目类别:
    University Undergraduate Student Research Awards
Engineering an Islet Thread from zwitterionically modified alginates for type 1 diabetes
利用两性离子改性藻酸盐设计胰岛丝,用于治疗 1 型糖尿病
  • 批准号:
    9910390
  • 财政年份:
    2018
  • 资助金额:
    $ 32.5万
  • 项目类别:
Engineering an Islet Thread from zwitterionically modified alginates for type 1 diabetes
利用两性离子改性藻酸盐设计胰岛丝,用于治疗 1 型糖尿病
  • 批准号:
    10402773
  • 财政年份:
    2018
  • 资助金额:
    $ 32.5万
  • 项目类别:
ALGIPRO - Alginates by Production Scale Fermentation and Epimerisation
ALGIPRO - 通过生产规模发酵和差向异构化生产海藻酸盐
  • 批准号:
    102148
  • 财政年份:
    2016
  • 资助金额:
    $ 32.5万
  • 项目类别:
    Collaborative R&D
Bioactive Alginates and Obesity
生物活性藻酸盐与肥胖
  • 批准号:
    BB/G00563X/1
  • 财政年份:
    2008
  • 资助金额:
    $ 32.5万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了