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.
"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). "
[Show abstract][Hide abstract] ABSTRACT: Abstract Novel aptamer-functionalized polyethylene glycol-polylactic acid (PEG-PLA) (APP) micelles were developed with the objective to target the transferrin receptor on brain endothelial cells. Flurbiprofen, a potential drug for therapeutic management of Alzheimer's disease (AD), was loaded into the APP micelles using the co-solvent evaporation method. Results indicated that 9.03% (w/w) of flurbiprofen was entrapped in APP with good retention capacity in vitro. Targeting potential of APPs was investigated using the transferring receptor-expressing murine brain endothelial bEND5 cell line. APPs significantly enhanced surface association of micelles to bEND5 cells as quantified by fluorescence spectroscopy. Most importantly, APPs significantly enhanced intracellular flurbiprofen delivery when compared to unmodified micelles. These results suggest that APP micelles may offer an effective strategy to deliver therapeutically effective flurbiprofen concentrations into the brain for AD patients.
Journal of Microencapsulation 03/2013; 30(7). DOI:10.3109/02652048.2013.778907 · 1.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Two polymeric excipients, typically used in enabling drug delivery approaches, are Gelucire 44/14 (a product of Gattefosse s.a, St Priest, France) and polysorbate 80; these are known to improve solubility of poorly water-soluble drugs and, hence, increase their effective bioavailability. In addition to the use of Gelucire 44/14 and polysorbate 80 as excipients in drugs, they are also widely used as cosmetic and food additives. In general, complex structures and compositions of drug excipients impact performance of the formulation in vivo and consequently affect drug absorption. Therefore, a comparison between excipients from different suppliers and batches to batch would provide an indication of the impact on drug product performance and also the study of the effectiveness of the system and any problems associated with the formulation. In this study, high resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) is used to compare two different batches of Gelucire 44/14 and polysorbate 80. With the high resolving power of FTICR MS, it was possible to differentiate between batches of excipients from differences in the identified components. The improved resolution offered by FTICR MS allowed assignment of four polymeric series differences in the two batches of polysorbate 80 and the presence of one compound and three polymeric series differences in the two batches of Gelucire 44/14. The increase in the number of components assigned in the excipients batch using FTICR-MS, compared to the numbers previously assigned by lower resolution TOF MS, underlines the importance of high resolution techniques in analysis of highly complex mixtures.
[Show abstract][Hide abstract] ABSTRACT: To develop poly(amino acid)s with temperature-sensitivity, a series of polyaspartamides with isopropylamide and hydroxyalkylamide pendant groups were synthesized by a successive aminolysis reaction of polysuccinimide. The structure of the resulting polymers was examined by 1H NMR and FT-IR. The polyaspartamide derivatives self-assembled into nanoparticles in water and showed sharp temperature-responsive phase transition behaviour. The phase transition temperature (Tp) could be modulated by the hydrophilic–hydrophobic balance of the copolymer controlled by altering the composition of both pendants. Besides, an antitumor agent, doxorubicin, was successfully loaded into the polymeric nanoparticles via a dialyzing method. The drug release profile was temperature-dependent accelerating significantly above the Tp and decelerating below the Tp. This easily prepared polymeric nanoparticle with excellent biocompatibility and tunable temperature responsiveness has significant potential for controlled drug release applications.
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