Interaction between Drug Loaded Polyaspartamide-Polylactide-Polysorbate Based Micelles and Cell Membrane Models: A Calorimetric Study

Dipartimento di Scienze del Farmaco, Università degli Studi di Catania , Viale A. Doria 6, 95125 Catania, Italy.
Molecular Pharmaceutics (Impact Factor: 4.38). 06/2011; 8(3):642-50. DOI: 10.1021/mp100445k
Source: PubMed


Amphiphilic biodegradable copolymers, for their ability to self-assemble into micelle-like aggregates, with a suitable loading capacity, are of emerging interest for the delivery of water-insoluble drugs. α,β-Poly[(N-hydroxyethyl)-dl-aspartamide] (PHEA) is suitable to obtain amphiphilic graft copolymers. These copolymers can be obtained starting from PHEA-ethylenediamine (PHEA-EDA) which is functionalized with polysorbate 80 (PS₈₀, like targeting residues to the brain) and polylactide (PLA, like hydrophobic chains) in order to obtain polymeric micelles of PHEA-EDA-PS₈₀-PLA potentially useful to release drugs to the central nervous system. In this paper, the interaction and absorption of PHEA-EDA-PS₈₀-PLA micelles loaded with (R)-flurbiprofen with biomembrane models, represented by multilamellar or unilamellar vesicles made of dimyristoylphosphatidylcholine, are investigated by means of differential scanning calorimetry technique. (R)-Flurbiprofen is the single enantiomer of the racemate flurbiprofen; the capacity of this nonsteroidal anti-inflammatory drug to reduce risk of Alzheimer's disease has been recently reported. Drug release from the micelles to the lipid vesicles has been investigated in simulated physiological fluid, and it resulted to be affected by the biomembrane model.

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    • "Because the micellar size is one of the properties which greatly influence the circulation time and organ distribution (Gaucher et al., 2005), we set the feeding ratio as 10% in the next step of experiments in order to narrow down the distribution of micellar size and improve the drug utilization efficiency. The results showed that the solubilization capacity of flurbiprofen was improved greatly (about 9%, Table 1), which is around two-fold compared to polyaspartamide–polylactide–polysorbate-based micelle-like aggregates (4%) reported previously (Sarpietro et al., 2011). "
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