The effect of self-assembly conditions on the size of di- and tri-block copolymer micelles: solicitation from response surface methodology

Abstract

The objective of this study was to assess the application of Response Surface Methodology in defining the effect of self-assembly condition on the average diameter of polymeric micelles. Di- and tri-block copolymers of poly(ethylene oxide)-b-poly(α-benzylcarboxylate-ϵ-caprolactone) (PEO-PBCL) and PBCL-b-poly(ethylene glycol)-b-PBCL (PBCL-PEG-PBCL) were synthesized through ring opening polymerization of α-benzyl-ε-carboxylate using MePEO or dihydroxy PEG as initiator, respectively. Polymeric micelles were formed through solubilization of block copolymers in acetone followed by drop-wise addition of this solution to water. Polymer concentration was changed and the intensity mean diameter of self-assembled structures was measured by dynamic light scattering. The experimental data were fitted to a mathematical model. The experimental conditions leading to the production of micelles of certain size (30, 60 or 90 nm for tri-block and 30 nm for di-block copolymers) was predicted. A good match between predicted and experimental data was observed. The results showed it would be possible to obtain micelles of certain size using block copolymers of different molecular weights or obtain micelles of different size at a given block copolymer molecular weight, by manipulating the polymer concentration. These observations show reproducible micelles of defined average diameter can be prepared by co-solvent evaporation by controlling the used polymer concentration.

Nanoencapsulation of Novel Inhibitors of PNKP for Selective Sensitization to Ionizing Radiation and Irinotecan and Induction of Synthetic Lethality

“…15,18 The diameter of polymeric micelles (20−100 nm) is a critical feature of these formulations for tumor accumulation by the enhanced permeability and retention (EPR) effect. 19,20 To further enhance the selectivity for tumor cells, targeting ligands specifically interacting with receptors overexpressed on cancer versus normal cells can be attached to the surfaces of polymeric micelles. 21,22 Epidermal growth factor receptor (EGFR) overexpression is frequently found in tumors such as colorectal, breast, and lung cancer.…”

“…Polymeric micelles are self-assembled amphiphilic block copolymers that are used for encapsulation, sustained release, and targeted delivery of poorly soluble drugs. − In aqueous solution, polymeric micelles consist of a hydrophobic core that can serve as a reservoir for encapsulation and delivery of hydrophobic compounds and a hydrophilic shell that can provide the nanocarrier with stealth properties, preventing its recognition and early elimination by a mononuclear phagocytic system. , The diameter of polymeric micelles (20–100 nm) is a critical feature of these formulations for tumor accumulation by the enhanced permeability and retention (EPR) effect. , …”