Overcoming the Road Blocks: Advancement of Block Copolymer Micelles for Cancer Therapy in the Clinic

Abstract

With countless preclinical studies on block copolymer micelles (BCMs) successfully demonstrating the superiority of these advanced drug delivery formulations over conventional formulations, it remains somehow discouraging that only a few have reached clinical evaluation and practice. With a critical eye, this review aims to compare and summarize the preclinical and clinical data available on several BCM formulations and to identify their primary role in drug delivery as "carrier" or "solubilizer". This review focuses on polymeric micelles that have reached clinical evaluation and/or are being pursued commercially. Where available, we aim to compare the pharmacokinetics, toxicity, and efficacy data obtained in preclinical studies to identify the factors that likely played a key role in a decision to move these formulations forward from the bench to a first-in-human trial. Finally, we summarize clinical data obtained to date, where available, and conclude with the impact that each formulation has had on patients in terms of safety and efficacy.

Imaging modification of colon carcinoma cells exposed to lipid based nanovectors for drug delivery: a scanning electron microscopy investigation

“…In the last decade translational nanomedicine has led to an evolution of drugs therapies, especially those using liposome and micelle based formulation. 42,43 Interesting effects on inhibition of cell proliferation using this class of formulations, as organic so nanovectors for the delivery of 5-FU or also in combination with doxorubicin, were reported. 44,45 In particular, a systematic time-dependent investigation by FE-SEM technique allowed visualization of the interactions between the proposed nanoformulations and the cells, and detection of any possible morphological changes induced by treatment with the drug containing nanovectors for the three selected cell lines.…”

How Does the Encapsulation of Porphyrinic Photosensitizers into Polymer Matrices Affect Their Self‐Association and Dynamic Properties?

“…Numerous polymer structures have been elaborated as potential carrier systems for porphyrinic drug delivery aimed at improving porphyrin stability under physiological conditions and enhancing cell uptake . In particular, biodegradable block copolymer micelles (BCMs) are promising drug‐delivery systems, and their properties have been widely studied . BCMs typically consist of amphiphilic polymer molecules with a hydrophobic block forming the micellar core and a hydrophilic block forming the micellar shell in aqueous solutions.…”

“…[16][17][18][19] In particular, biodegradable block copolymer micelles (BCMs) are promising drug-delivery systems, and their properties have been widely studied. [20][21][22] BCMs typically consist of amphiphilic polymer molecules with ah ydrophobic block formingt he micellar corea nd ah ydrophilic block forming the micellar shell in aqueous solutions. Several properties render the use of BCMs advantageous for drug delivery:1 )due to sizes in the nanometer range, they may increaset umor tissue uptake by the enhanced permeability and retention (EPR) effects of the tumor vasculature; [20] 2) hydrophobic drugs can be accommodated in the core of BCMs and can be transported in the blood;3 )the outer blocks of BCMs consist of hy-Photodynamic therapy (PDT) with porphyrinic photosensitizers largely relies on efficient drug formulations to prevent porphyrin aggregation andt oe nhancewater solubility and stabilityi n physiologic environments.…”

Investigating the influence of aromatic moieties on the formulation of hydrophobic natural products and drugs in poly(2-oxazoline) based amphiphiles

“…[10] These major problems concerning nanoformulations, drug delivery and the advancement of polymeric micelles for clinical cancer therapy were also critically reviewed by other researchers. [11][12][13] Polymer micelles comprising a poly(2-oxazoline) (POx) based amphiphilic triblock copolymer (poly(2-methyl-2-oxazoline)-block-poly(2-butyl-2-oxazoline)-block-poly(2-methyl-2-oxazoline) (PMeOx-b-PBuOx-b-PMeOx ≡ A-pBuOx-A)) constitute an unusual exception.…”