A Comparative Evaluation of Hydroxycamptothecin Drug Nanorods With and Without Methotrexate Prodrug Functionalization for Drug Delivery

Abstract

We developed a novel self-targeted multi-drug co-delivery system based on rod-shaped 10-hydroxycamptothecin (CPT) nanoanticancer drug (CPT NRs) followed by a surface functionalization with self-targeting PEGylated lipid-conjugated methotrexate (MTX) pro-anticancer drug. The self-targeting effect and in vitro cell viability of the MTX-PEG-CPT NRs on HeLa cells were demonstrated by comparative cellular uptake and MTT assay of the PEG-CPT NRs. In vitro studies showed the feasibility of using this high drug-loading MTX-PEG-CPT NRs in self-targeted drug delivery, controlled-/sustained-release, and synergistic cancer therapy. More importantly, this work would stimulate interest in the use of PEGylated lipid-conjugated MTX by introducing an early-phase tumor-targeting role and then driving a late-phase anticancer role for the highly convergent design of nanomulti-drug, which may advantageously offer a new and simple strategy for simultaneously targeting and treating FA receptor-overexpressing cancer cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s11671-016-1599-y) contains supplementary material, which is available to authorized users.

Nanoparticles Based on Novel Carbohydrate-Functionalized Polymers

“…Although the conjugation of pharmaceutical agents with PEG has brought significant improvements such as an increased solubility in water, prolonged liberation rates, and reduction of toxicity, problems such as the necessity for high doses and drug resistance are still awaiting resolution. Multi-therapy presents itself as a viable solution since polymeric pro-drugs are able to form nanoparticles that are able to encapsulate a different drug, allowing the reduction of administered doses, and consequently an increased therapeutic efficiency [39][40][41].…”

“…Carbon spectrum confirmed these results, mainly by the presence of the anomeric carbon at 98.8 ppm and triazole signal at 124.9 ppm. Matrix-Assisted Laser Desorption/Ionization with Time-of-Flight analyser (MALDI-TOF) mass spectrum presented a medium mass/charge of 1512, where the expected value was 1401 m/z., which result is within the range for (C 2 H 4 O) n H 2 O, with n = 21-24. therapy presents itself as a viable solution since polymeric pro-drugs are able to form nanoparticles that are able to encapsulate a different drug, allowing the reduction of administered doses, and consequently an increased therapeutic efficiency [39][40][41]. Esterification of coumarin 3-carboxylic acid with PEG using N,N-dicyclohexylcarbodiimide (DCC), and catalytic 4-dimethylaminepyridine (DMAP, Scheme 7) afforded the fluorescent polymer 17 in excellent yield.…”

Lipidic Liquid Crystalline Cubic Phases and Magnetocubosomes as Methotrexate Carriers

“…In light of the systemic side effects of anticancer drugs, the design of drug carriers is very important. There are several methods for limiting MTX toxicity through its administration by means of carriers or targeting carriers, e.g., liposomes [7,8], silica materials [9,10], lipid nanoparticles [11,12], chitosan nanoparticles [13], polymeric micelles with magnetic nanoparticles [14], nanorods [15], implants [16], and nanogels [17,18].…”

Hybrid delivery systems for methotrexate-lipidic liquid crystalline cubic phases and cubosomes with magnetic nanoparticles

“…[3][4][5][6] In view of the systemic side-effects of anticancer drugs, the design of drug carriers is very important. There are several methods for limiting MTX toxicity through its administration by means of carriers or targeting carriers, e.g., liposomes [7,8], silica materials [9,10], lipid nanoparticles [11,12], chitosan nanoparticles [13], polymeric micelles with magnetic nanoparticles [14], nanorods [15], implants [16] and nanogels [17,18].…”