Poly-l-arginine grafted PAMAM dendrimers for the brain delivery of Temozolomide in the management of Glioblastoma multiforme: In-vitro and In-vivo evaluation

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Delivery Science and Technology Pub Date : 2025-09-11 DOI:10.1016/j.jddst.2025.107526

Rakesh Kumar Sahoo , Kushagra Nagori , Ajazuddin , Biswajit Naik , Dhaneswar Prusty , Rishi Paliwal , Umesh Gupta

{"title":"Poly-l-arginine grafted PAMAM dendrimers for the brain delivery of Temozolomide in the management of Glioblastoma multiforme: In-vitro and In-vivo evaluation","authors":"Rakesh Kumar Sahoo , Kushagra Nagori , Ajazuddin , Biswajit Naik , Dhaneswar Prusty , Rishi Paliwal , Umesh Gupta","doi":"10.1016/j.jddst.2025.107526","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><div>Glioblastoma multiforme (GBM) is one of the most aggressive and pervasive forms of malignant primary brain tumor. The objective is to develop an energy and receptor independent nanocarrier for the management of GBM.</div></div><div><h3>Methods</h3><div>In the present work, pArg was conjugated on to the surface of PAMAM dendrimers as per the findings of <em>in-silico</em> molecular docking study, followed by TMZ encapsulation. Den-pArg conjugate was synthesized at 1:8 ratio as per binding affinity analysis and successfully characterized by <sup>1</sup>H NMR.</div></div><div><h3>Results</h3><div>The average particle size and entrapment efficiency of TMZ@Den-pArg were 198.72 ± 14.96 nm and 72.12 ± 5.81 %, respectively. TMZ@Den-pArg was biocompatible and showed sustained and controlled drug release up to 48 h in acidic environment. TMZ@Den-pArg resulted in maximum cytotoxic effect against both U87MG and LN229 cells. In comparison to pure TMZ, plasma half-life (t<sub>1/2</sub>) of TMZ@Den-pArg (7.04 ± 0.81 h) was enhanced by almost 3 times in healthy rats. After 4 h of administration, the TMZ@Den-pArg resulted in significantly (p < 0.0001) higher accumulation in cerebrum (28.51 ± 2.12 ng per g of brain) than cerebellum. Den-pArg reduced the drug distribution to heart and kidney.</div></div><div><h3>Conclusions</h3><div>The findings suggested that polyarginine conjugated PAMAM dendrimers can be a potential nanocarrier for the brain delivery of chemotherapeutic agents.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107526"},"PeriodicalIF":4.9000,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Drug Delivery Science and Technology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1773224725009293","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

Abstract

Purpose

Glioblastoma multiforme (GBM) is one of the most aggressive and pervasive forms of malignant primary brain tumor. The objective is to develop an energy and receptor independent nanocarrier for the management of GBM.

Methods

In the present work, pArg was conjugated on to the surface of PAMAM dendrimers as per the findings of in-silico molecular docking study, followed by TMZ encapsulation. Den-pArg conjugate was synthesized at 1:8 ratio as per binding affinity analysis and successfully characterized by ¹H NMR.

Results

The average particle size and entrapment efficiency of TMZ@Den-pArg were 198.72 ± 14.96 nm and 72.12 ± 5.81 %, respectively. TMZ@Den-pArg was biocompatible and showed sustained and controlled drug release up to 48 h in acidic environment. TMZ@Den-pArg resulted in maximum cytotoxic effect against both U87MG and LN229 cells. In comparison to pure TMZ, plasma half-life (t_1/2) of TMZ@Den-pArg (7.04 ± 0.81 h) was enhanced by almost 3 times in healthy rats. After 4 h of administration, the TMZ@Den-pArg resulted in significantly (p < 0.0001) higher accumulation in cerebrum (28.51 ± 2.12 ng per g of brain) than cerebellum. Den-pArg reduced the drug distribution to heart and kidney.

Conclusions

The findings suggested that polyarginine conjugated PAMAM dendrimers can be a potential nanocarrier for the brain delivery of chemotherapeutic agents.

Abstract Image

查看原文本刊更多论文

poly -l-精氨酸移植PAMAM树状大分子用于替莫唑胺脑递送治疗多形性胶质母细胞瘤：体外和体内评估

目的多形性胶质母细胞瘤（GBM）是最具侵袭性和广泛性的原发性恶性脑肿瘤之一。目的是开发一种能量和受体独立的纳米载体，用于治疗GBM。方法根据分子对接研究结果，将pArg偶联到PAMAM树状大分子表面，然后进行TMZ包封。根据结合亲和力分析，以1:8的比例合成了Den-pArg缀合物，并通过1H NMR对其进行了表征。结果TMZ@Den-pArg的平均粒径为198.72±14.96 nm，捕集效率为72.12±5.81%。TMZ@Den-pArg具有生物相容性，并在酸性环境中表现出长达48小时的持续和控制药物释放。TMZ@Den-pArg对U87MG和LN229细胞均产生最大的细胞毒作用。与纯TMZ相比，TMZ@Den-pArg的血浆半衰期（t1/2）（7.04±0.81 h）提高了近3倍。给药4小时后，TMZ@Den-pArg在大脑中的积累量（28.51±2.12 ng / g脑）显著高于小脑（p < 0.0001）。Den-pArg减少了药物在心脏和肾脏的分布。结论聚精氨酸缀合PAMAM树状大分子可能是一种潜在的化学药物脑递送纳米载体。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Drug Delivery Science and Technology 医学-药学

CiteScore

8.00

自引率

8.00%

发文量

879

审稿时长

94 days

期刊介绍： The Journal of Drug Delivery Science and Technology is an international journal devoted to drug delivery and pharmaceutical technology. The journal covers all innovative aspects of all pharmaceutical dosage forms and the most advanced research on controlled release, bioavailability and drug absorption, nanomedicines, gene delivery, tissue engineering, etc. Hot topics, related to manufacturing processes and quality control, are also welcomed.