TY - JOUR
T1 - Enhanced stability of PEG- block -poly(N -hexyl stearate l -aspartamide) micelles in the presence of serum proteins
AU - Diezi, Thomas A.
AU - Bae, Younsoo
AU - Kwon, Glen S.
PY - 2010/8/2
Y1 - 2010/8/2
N2 - Polyethylene glycol-phospholipid micelles form a major class of nanocarriers in pharmacy and medicine due to proven capability in drug solubilization, sustained drug release, and evidence for targeted drug delivery in vivo. In this report, we have prepared micelles composed of PEG-block-poly(N-hexyl stearate l-aspartamide) (PEG-b-PHSA), having nine stearic acid side chains, and have studied their stability in the presence of serum proteins by FoÌ̂rster resonance energy transfer (FRET) experiments. In the presence of serum albumin, alpha and beta globulins, or gamma globulins, there are minimal changes in FRET over two hours in vitro, indicating integrity of PEG-b-PHSA micelles. In contrast, 1,2-distearoyl-sn-glycero-3- phosphoethanolamine-N-[amino(polyethylene glycol)-5000] (PEG-DSPE) micelles lose FRET over two hours in vitro, especially in the presence of alpha and beta globulins, indicating the disruption of PEG-DSPE micelles and leakage of fluorescent probes. Owing to the aliphatic nature of DSPE and PHSA, both PEG-b-PHSA and PEG-DSPE micelles efficiently solubilize amphotericin B (AmB), a poorly water-soluble antifungal agent used to combat systemic mycoses. However, only PEG-b-PHSA micelles gradually liberate AmB in the presence of alpha and beta globulins, based on time-dependent changes in the self-aggregation state of AmB, monitored by UV/vis spectroscopy. PEG-b-PHSA micelles are remarkably stable in the presence of serum proteins and a more stable alternative for poorly water-soluble drugs, which have been solubilized by PEG-DSPE micelles.
AB - Polyethylene glycol-phospholipid micelles form a major class of nanocarriers in pharmacy and medicine due to proven capability in drug solubilization, sustained drug release, and evidence for targeted drug delivery in vivo. In this report, we have prepared micelles composed of PEG-block-poly(N-hexyl stearate l-aspartamide) (PEG-b-PHSA), having nine stearic acid side chains, and have studied their stability in the presence of serum proteins by FoÌ̂rster resonance energy transfer (FRET) experiments. In the presence of serum albumin, alpha and beta globulins, or gamma globulins, there are minimal changes in FRET over two hours in vitro, indicating integrity of PEG-b-PHSA micelles. In contrast, 1,2-distearoyl-sn-glycero-3- phosphoethanolamine-N-[amino(polyethylene glycol)-5000] (PEG-DSPE) micelles lose FRET over two hours in vitro, especially in the presence of alpha and beta globulins, indicating the disruption of PEG-DSPE micelles and leakage of fluorescent probes. Owing to the aliphatic nature of DSPE and PHSA, both PEG-b-PHSA and PEG-DSPE micelles efficiently solubilize amphotericin B (AmB), a poorly water-soluble antifungal agent used to combat systemic mycoses. However, only PEG-b-PHSA micelles gradually liberate AmB in the presence of alpha and beta globulins, based on time-dependent changes in the self-aggregation state of AmB, monitored by UV/vis spectroscopy. PEG-b-PHSA micelles are remarkably stable in the presence of serum proteins and a more stable alternative for poorly water-soluble drugs, which have been solubilized by PEG-DSPE micelles.
KW - Amphotericin B
KW - FRET
KW - PEG-DSPE
KW - drug solubilization
KW - micelle stability
KW - polymeric micelle
UR - http://www.scopus.com/inward/record.url?scp=77955251550&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955251550&partnerID=8YFLogxK
U2 - 10.1021/mp100069p
DO - 10.1021/mp100069p
M3 - Article
C2 - 20575526
AN - SCOPUS:77955251550
SN - 1543-8384
VL - 7
SP - 1355
EP - 1360
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
IS - 4
ER -