Formulation of Fenretinide Nanoparticles for Enhanced Bioavailability

芬维A胺纳米颗粒的制剂可增强生物利用度

• 批准号: 8536879
• 负责人: Levon Bostanian
• 金额: $ 10.47万
• 依托单位: XAVIER UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8536879
• 关键词: Adverse effects; Applications Grants; Basic Science; Biological Availability; Biological Products; Caco-2 Cells; Cancer Patient; Cell Line; Cell membrane; Cell model; Childhood; Classification; Data; Development; Differential Scanning Calorimetry; Disease; Dosage Forms; Dose; Drug Delivery Systems; Drug Formulations; Electron Microscope; Evaluation; Exhibits; Faculty; Fenretinide; Fostering; Funding; Human; In Vitro; Incidence; Innovative Therapy; Intestines; Laboratories; Literature; Malignant Neoplasms; Mentors; Methods; Microscopy; Minority; Modeling; Morphology; Nanotechnology; Neoplasms; Neuroblastoma; Oral; Oral Administration; Particle Size; Patients; Permeability; Pharmaceutical Preparations; Plasma; Preparation; Principal Investigator; Property; Public Health; Publications; Recurrent disease; Relapse; Reporting; Research; Research Activity; Research Design; Residual Tumors; Retinoids; Scanning; Solubility; Staging; Students; Sympathetic Nervous System; System; Testing; Therapeutic; Training Programs; Translational Research; Universities; Work; X ray diffraction analysis; absorption; base; cancer therapy; capsule; compliance behavior; improved; in vitro activity; in vivo; innovation; interdisciplinary approach; member; nano; nanoparticle; novel; outcome forecast; particle; pressure; programs; skills; therapeutic effectiveness; water solubility

DESCRIPTION (provided by applicant): Neuroblastoma, a neoplasm of the sympathetic nervous system, is the second most common malignant tumor in childhood. In recent years, prognosis for patients with this neoplasm has improved, but the overall 5- year survival is still less than 60% because of fatal relapses of the disease. However, the incidence of fatal relapses can be reduced by adding innovative therapy to eradicate the residual disease. Complete eradication of the residual disease requires long-term treatment during the early stages. Fenretinide, a synthetic retinoid, is the focus of long-term treatment for complete eradication of the disease. The drug has been successfully tested for antitumor activity in vitro and in vivo. However, the potential of fenretinide as a long-term treatment for childhood neuroblastoma is limited by its poor water solubility and poor bioavailability following oral administration. The overall objective of this project is to develop fenretinide nanoparticles. The central hypothesis i that the bioavailability of fenretinide will be significantly enhanced due to the small size of the nanoparticles and their enhanced ability to penetrate cell membranes. The following four specific aims delineate the step-wise approach towards the testing of the central hypothesis. Specific Aim 1. Preparation of nanoparticle formulations. Two different nanoparticle formulations will be prepared using a laboratory nanospray dryer and a high pressure homogenizer, respectively. Specific Aim 2. Characterization of the nanoparticles. Specific Aim 3. Evaluation of the in vitro drug release. Specific Aim 4. Evaluation of the intestinal permeability of fenretinide using a Caco-2 cell model. The proposed research is innovative, in our opinion, because there are no reports in the literature of using the Nano Spray Dryer or high pressure homogenizer to produce nanoparticles of fenretinide. We expect that the bioavailability of fenretinide will be enhanced by its formulation in the form of nanoparticles, and as a result, lower doses of the drug will be needed to achieve therapeutic plasma concentrations. Lowering the drug dose will also reduce the incidence of adverse side effects and enhance patient compliance. The proposed project will help the principal investigator develop his skills in nanotechnology and the formulation of nanoparticles of drug substances. It will help him enhance his publication record and, therefore, strengthen his ability to submit competitive grant applications. The proposed project will also increase the exposure of minority students to research by working in conjunction with a training program funded by the Center of Excellence program at the university, which requires the mentor to be a faculty member involved in research.

描述（由申请人提供）：神经母细胞瘤是一种交感神经系统的肿瘤，是儿童第二常见的恶性肿瘤。近年来，该肿瘤患者的预后有所改善，但由于疾病的致命复发，总体5年生存率仍低于60%。然而，致命性复发的发生率可以通过添加创新疗法来根除残留的疾病来降低。彻底根除残留疾病需要在早期阶段进行长期治疗。芬拉啶是一种合成类维甲酸，是彻底根除这种疾病的长期治疗重点。该药物已成功地在体外和体内进行了抗肿瘤活性试验。然而，芬维啶作为儿童神经母细胞瘤长期治疗的潜力受到口服给药后水溶性差和生物利用度差的限制。该项目的总体目标是开发芬维甲酸纳米颗粒。中心假设是，芬瑞啶的生物利用度将显著提高，由于小尺寸的