Abstract Peptide based drugs are an important class of therapeutic agents but their development into commercial products is often hampered due to their inherent physico‐chemical and biological instabilities. Phospholipid micelles can be used to address these delivery concerns. Peptides self‐associate with micelles that serve to thwart the aggregation of these biomolecules. Self‐association with micelles does not modify the peptide chemically; therefore the process does not denature or compromise the bioactivity of peptides. Additionally, many amphiphilic peptides adopt α‐helical conformation in phospholipid micelles which is not only the most favorable conformation for receptor interaction but also improves their stability against proteolytic degradation, thus making them long‐circulating. Furthermore, the nanosize of micelles enables passive targeting of peptides to the desired site of action through leaky vasculature present at tumor and inflamed tissues. All these factors alter the pharmacokinetic and biodistribution profiles of peptides therefore enhance their efficacy, reduce the dose required to obtain a therapeutic response and prevent adverse effects due to interaction of the peptide with receptors present in other physiological sites of the body. These phospholipid micelle based peptide nanomedicines can be easily scaled‐up and lyophilized, thus setting the stage for further development of the formulation for clinical use. All things considered, it can be concluded that phospholipid micelles are a safe, stable and effective delivery option for peptide drugs and they form a great promise for future peptide nanomedicines. WIREs Nanomed Nanobiotechnol 2012, 4:562–574. doi: 10.1002/wnan.1185 This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Peptide-Based Structures
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Evaluation of change in arterial blood pressure upon administration of vasoactive intestinal peptide (VIP). Effect on the mean arterial blood pressure in mice treated with VIP in micelles (▪) and VIP alone (□). (Reprinted with permission from Ref 65. Copyright 2005 Elsevier)
Vasodilation of arteries in hamster cheek pouch upon VIP suffusion. Effect of VIP suffusion on the arteriolar diameter of hamster cheek pouch. Open circles represent VIP in saline and closed circles represent VIP‐SSM; *P < 0.05 in comparison to baseline and †P < 0.05 in comparison to VIP in saline. (Reprinted with permission from Ref 61. Copyright 1999 Springer)
Analysis of stability of NPY against enzymatic degradation. Representative mass spectra of (a) NPY in saline, (b) NPY in saline incubated with DPP‐4, (c) NPY in SSM, and (d) NPY in SSM incubated with DPP‐4. (Reprinted with permission from Ref 53. Copyright 2011 Elsevier)
Secondary structure of secretin in the presence or absence of SSM. Representative circular dichroism spectra of secretin in saline and in SSM. (Reprinted with permission from Ref 64. Copyright 2002 Elsevier)
Representative particle size distribution of (a) SSM; (b) NPY in saline; and (c) NPY‐SSM. Hydrodynamic particle size distribution of (a) SSM (14 ± 3 nm), (b) NPY in saline (557 ± 100 nm) and (c) NPY‐SSM (15 ± 3 nm). (Reprinted with permission from Ref 53. Copyright 2011 Elsevier)
Diagrammatic representation of formation of sterically stabilized micelles (SSM) based peptide nanomedicine. DSPE‐PEG2000 self‐aggregate to form SSM when dispersed in aqueous media at lipid concentration above their CMC. Peptides added to these micelles self‐associate to form SSM‐peptide nanomedicine.
Representation of DSPE‐PEG2000 monomer and SSM prepared in presence and absence of sodium chloride in aqueous media. Molecular dynamics simulations showing snapshots of PEGylated phospholipid monomer and equilibrated micelles in pure water or in HEPES buffered saline (0.166 M NaCl) with their corresponding aggregation number. The hydrodynamic size of micelles prepared in the presence or absence of NaCl was observed to be 5.9 and 13.9 nm, respectively. (Reprinted with permission from Ref 45. Copyright 2011 ACS Publications)
