Polymeric micelles from poly(ethylene glycol)–poly(amino acid) block copolymer for drug and gene delivery

Abstract

Dramatic advances in biological research have revealed the mechanisms underlying many diseases at the molecular level. However, conventional techniques may be inadequate for direct application of this new knowledge to medical treatments. Nanobiotechnology, which integrates biology with the rapidly growing field of nanotechnology, has great potential to overcome many technical problems and lead to the development of effective therapies. The use of nanobiotechnology in drug delivery systems (DDS) is attractive for advanced treatment of conditions such as cancer and genetic diseases. In this review paper for a special issue on biomaterial research in Japan, we discuss the development of DDS based on polymeric micelles mainly in our group for anti-cancer drug and gene delivery, and also address our challenges associated with developing polymeric micelles as super-functionalized nanodevices with intelligent performance.

Peptide-Based Polymer Therapeutics

“…The hydrophilic palisade helps the system to stay unrecognised along blood circulation. PEG is usually selected as the shell-forming segment because of its physicochemical characteristics, including high water solubility through steric stabilisation, significant chain mobility, lower toxicity and a stealth effect on the polymeric micelles preventing the adsorption of proteins [122]. Polymeric micelles have demonstrated good stability at low concentrations, adequate size for systemic drug delivery, useful out-shell emplacement for active targeting and feasibility for multiple drug incorporation towards combination therapy applications [123].…”

“…The future of these systems implies novelties in their design, such as cross-linking by reversible bonds with stimuli-responsive futures at the site of action [134] and the inclusion of targeting moieties which could enhance cellular uptake, in particular diseased cells through receptor-mediated endocytosis. All these systems are defined as a second generation of polymer therapeutics where their intrinsic characteristics may further improve the therapeutic index and reduce side effects [122].…”

Polymer–metal complex nanoparticles-containing cisplatin and amphiphilic block copolymer for anticancer drug delivery

“…The incorporation of citric acid blocks into the polycaprolactone chain ends was confirmed by the elimination of resonance from the hydroxyl terminations of PCL at 3.6 ppm and appearance of a new resonance from the CH 2 of citryl units located in terminal groups of CH 2 -COOH at 2.6-3 ppm in the 1 H NMR spectrum of copolymer. Compositions of the block copolymers were determined by 1 H NMR in d 6 -DMSO from peak intensity ratios of methylene protons of terminal citryl units (CH 2 -COOH: a quartet at 2.62-2.77 ppm) and methylene protons next to the oxygen of PCL chain (CH 2 -O: a triplet at 4 ppm). From 1 H NMR of PCA-b-PCL-b-PCA in D 2 O, complete loss of characteristic resonance originating from CL was found due to the suppressed molecular motion of the aggregated hydrophobic PCL chains in the inner cores which offered one of the evidences that PCA-PCL-PCA copolymers can associate to form micellar structure in the water.…”

“…Therefore, many efforts have been devoted to develop a DDS aimed at increasing the blood circulation period and accumulation in solid tumors. [6][7][8] The association of cisplatin with long-circulating nano-sized carriers like polymer conjugates, liposomes, micelles and dendrimers alters drug pharmacokinetics and results in increased drug accumulation in tumors, based on the 'enhanced permeability and retention' (EPR) effect. The EPR effect is a result of leaky capillaries adjacent to solid tumors and a lack of a lymphatic system for the drainage of drugs back to the systemic circulation.…”

“…The resultant micelles incorporating cisplatin were shown to have favorable pharmacokinetics, tumor-specific accumulation, improved antitumor activity and reduced nonspecific side effects, relative to the free drug. [6,24,25] Polymer micelles with crosslinked ionic cores formed from poly (ethylene oxide)-bpoly methacrylate anions (PEO-b-PMA) were employed for the preparation of polymer-cisplatin conjugates. The drug content in the cross-linked micelles was determined to be 22% (w/w).…”