Poloxamer 407 based-nanoparticles for controlled release of methotrexate

Abstract

Poloxamer 407 (P407)-based nanoparticles were produced by the high pressure homogenization method for the encapsulation and delivery of methotrexate (MTX), aiming intravenous therapeutic applications. The surface of these nanoparticles was functionalized by conjugation of P407 with folic acid (FA) or with MTX, which served as targeting ligand agents. MTX-P407 conjugate was also developed to increase the final drug cargo. Two hydrophobic derivatives of MTX, MTX di-ethylated ester (MTX-OEt) and the ionic complex MTX-dimethyldioctadecylammonium bromide (MTX-DODAB) were produced and entrapped onto P407-based nanoparticles. All formulations developed revealed a monodisperse character comprising small and narrow nanoparticles (< 100 nm). P407 nanoparticles (functionalized with FA) and MTX-P407 nanoparticles, both loaded with MTX-OEt, demonstrated a slow drug release profile. The effect of lipase from Aspergillus oryzae on the hydrolysis of the linkage between the P407 and MTX, and consequent MTX release profile, was also evaluated. We observed a controlled and slow release of MTX (< 50% of release after 11 days) in the presence of enzyme. These MTX-P407 nanoparticles loaded with MTX-OEt induced a great effect against Caco-2 cancer cells (≈40% of cell death after 72 h of incubation), demonstrating higher efficiency than the free MTX at the same concentration.

Microfluidic Technology for the Production of Hybrid Nanomedicines

“…This is valid not only for droplet microfluidics, now widely applied to high-throughput screenings [41][42][43][44][45], but also for NMed preparations. Triblock polymers such as Pluronics ® have been demonstrated to be safe and biocompatible [46,47] and are frequently used as stabilizers during the formation of NMeds both in benchtop [48][49][50][51] and in microfluidic based protocols [52][53][54][55]. For this reason, we standardized the use of Pluronic ® F68 as already exploited in our optimized benchtop methods to be used with the microfluidic device.…”

A Critical Review of the Use of Surfactant-Coated Nanoparticles in Nanomedicine and Food Nanotechnology

“… [ 399 ] Enhancement of anti-cancer activity Methotrexate-poloxamer 407 conjugate, folic acid-poloxamer 407 conjugate Vegetable oil 91.3 ± 24.4 Methotrexate Caco-2 cells Vegetable oil nanoparticles coated with methotrexate-poloxamer 407 conjugate showed a stronger anticancer effect compared to the group coated with Folic acid-poloxamer 407 conjugate. [ 400 ] Enhancement of anti-cancer activity Polysorbate 80 Poly (butyl cyanoacrylate) 210 ± 10.01 nm Doxorubicin Male Wistar rats imigrated glioblastoma tissue (intraperitoneal administration) Rats administered with polysorbate 80 coated poly (butyl cyanoacrylate) nanoparticles containing doxorubicin survived for more than 180 days (post tumor implantation). [ 401 ] Enhancement of anti-cancer activity Poloxamer 188 Human IgG 140.2 ± 2.4 nm Albino male Wistar rats (160–180 g), metastatic models of chemically induced non-small cell lung cancer (intravenous administration of A549 cells) Nanoparticles consisting of human IgG and poloxamer 188 were prepared by encapsulating siRNA.…”

A Quantum Mechanics and Molecular Mechanics Study of the Effects of Different Solvents and Temperatures on the Connections of Methotrexate Derivatives Anticancer Drug to Nanotubes Carriers

“…Various modifications in the glutamic acid moiety have been reported with the aim of decreasing the formation rate of poly-γ-glutamates in normal cells; they include: substitution of γ-carboxyl with amide or peptide groups and replacement of glutamic acid with other amino acids; these steps have been taken with the goal of generating a new class of antitumor agents. We prepared several MTX derivatives containing R-or γ-substituted glutamic acids [32]. The lysine and ornithine derivatives were synthesized from MTX, and both derivatives had selfsame bindings [33].…”