2022 journal article

Tissue-reactive drugs enable materials-free local depots

JOURNAL OF CONTROLLED RELEASE, 343, 142–151.

By: S. Pandit n, S. Palvai n, N. Massaro n, J. Pierce n  & Y. Brudno n 

author keywords: Sustained release; Materials-free delivery; Paclitaxel; Pancreatic cancer; Extracellular matrix; N-hydroxysuccinimide ester
MeSH headings : Animals; Cell Line, Tumor; Drug Delivery Systems; Drug Liberation; Hydrogels; Mice; Paclitaxel; Pancreatic Neoplasms / drug therapy
TL;DR: It is demonstrated that locally injected TRAPs create dispersed, stable intratumoral depots deep within mouse and human pancreatic tumor tissues, and had better solubility than free paclitaxel and enabled sustained in vitro and in vivo drug release. (via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being (Web of Science; OpenAlex)
Source: Web Of Science
Added: May 2, 2022

Local, sustained drug delivery of potent therapeutics holds promise for the treatment of a myriad of localized diseases while eliminating systemic side effects. However, introduction of drug delivery depots such as viscous hydrogels or polymer-based implants is highly limited in stiff tissues such as desmoplastic tumors. Here, we present a method to create materials-free intratumoral drug depots through Tissue-Reactive Anchoring Pharmaceuticals (TRAPs). TRAPs diffuse into tissue and attach locally for sustained drug release. In TRAPs, potent drugs are modified with ECM-reactive groups and then locally injected to quickly react with accessible amines within the ECM, creating local drug depots. We demonstrate that locally injected TRAPs create dispersed, stable intratumoral depots deep within mouse and human pancreatic tumor tissues. TRAPs depots based on ECM-reactive paclitaxel (TRAP paclitaxel) had better solubility than free paclitaxel and enabled sustained in vitro and in vivo drug release. TRAP paclitaxel induced higher tumoral apoptosis and sustained better antitumor efficacy than the free drug. By providing continuous drug access to tumor cells, this material-free approach to sustained drug delivery of potent therapeutics has the potential in a wide variety of diseases where current injectable depots fall short.