Supramolecular assemblies based on copolymers of PEG600 and functionalized aromatic diesters for drug delivery applications

J Am Chem Soc. 2004 Sep 1;126(34):10640-4. doi: 10.1021/ja039651w.

Abstract

A chemoenzymatic approach has been developed to synthesize poly(ethylene glycol)-based amphiphilic copolymers under mild reaction conditions that self-assemble in aqueous media to form polymeric nanomicelles in the range of 20-50 nm. The supramolecular organization of polymeric nanomicelles was studied by 1H NMR longitudinal relaxation time (T1) and light scattering techniques (static and dynamic). Interestingly, the enzyme novozyme-435 plays an important role in controlling the polymerization and distribution of polymer chains, which is critical for the formation of nanomicelles with unimodal distributions. The methodology developed is highly flexible as it allows the introduction of various functionalities in the polymeric nanomicelles. These self-organized nanomicelles are highly efficient drug delivery vehicles for hydrophobic and partially hydrophilic drugs, both transdermally and orally, as they have the ability to encapsulate guest molecules during self-organization. In vivo studies by encapsulating anti-inflammatory agents (aspirin and naproxen) in these polymeric nanomicelles and by applying topically resulted in significant reduction in inflammation. The % reduction in inflammation using polymeric nanomicelles containing aspirin and naproxen was 62 and 64%, respectively.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Aspirin / administration & dosage
  • Aspirin / chemistry*
  • Chemistry, Pharmaceutical
  • Drug Delivery Systems / methods*
  • Enzymes, Immobilized
  • Fungal Proteins
  • Hydrophobic and Hydrophilic Interactions
  • Inflammation / drug therapy
  • Lipase / chemistry
  • Mice
  • Micelles
  • Nanotechnology
  • Polyesters / chemical synthesis*
  • Polyesters / chemistry
  • Polyethylene Glycols / chemical synthesis*
  • Polyethylene Glycols / chemistry
  • Spectrophotometry, Ultraviolet

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Enzymes, Immobilized
  • Fungal Proteins
  • Micelles
  • Polyesters
  • Polyethylene Glycols
  • Novozyme 435
  • Lipase
  • Aspirin