Growth, shrinking, and breaking of pluronic micelles in the presence of drugs and/or beta-cyclodextrin, a study by small-angle neutron scattering and fluorescence spectroscopy.
The associative structures between F127 Pluronic micelles and four drugs, namely, lidocaine (LD), pentobarbital sodium salt (PB), sodium naproxen (NP), and sodium salicylate (SAL), were studied by small-angle neutron scattering (SANS). Different outcomes for the micellar aggregates are observed, which are dependent on the chemical nature of the drug and the presence of charge or otherwise: the micelles grow with LD, are hardly modified with PB, and decrease in size with both NP and SAL. The partition coefficient, determined by fluorescence spectroscopy, is directly correlated to the amount of charge, following NP approximately SAL < PB < LD. All drugs are found to lie at the interfacial layer, with a slightly deeper localization of LD and more superficial for PB. All drugs can form inclusion complexes with heptakis(2,6-di-O-methyl) beta-cyclodextrin (hep2,6 beta-CD). Hep2,6 beta-CD, as shown in previous studies (Joseph, J.; Dreiss, C. A.; Cosgrove, T. Langmuir, 2008, 24, 10005-10010; Dreiss, C. A.; Nwabunwanne, E.; Liu, R.; Brooks, N. J. Soft Matter, 2009, 5, 1888-1896), is also able to form a complex with F127, resulting in micellar breakup. In the ternary mixtures, a fine balance of forces is involved, which results in drastic micellar changes, as observed from the SANS patterns. Depending on the ratio of drug, polymer, and hep2,6 beta-CD and the nature of the interactions (which is directly linked to the drug chemical structure), the presence of drug either hinders micellar breakup by beta-CD (at high enough concentration of LD or PB) or leads to micellar growth (NP). These effects are mainly attributed to a preferential drug/beta-CD interaction (except for PB), which, at least in the conditions studied here, explains the higher beta-CD concentration needed for micellar breakup to occur.
Valero
Margarita
M
Dpto. Química Física, Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno, s/n, 37007 Salamanca, Spain.
Dreiss
Cécile A
CA
D008012:Lidocaine / Q000737:chemistry; D008823:Micelles; D015394:Molecular Structure; D009288:Naproxen / Q000737:chemistry; D010424:Pentobarbital / Q000737:chemistry; D020442:Poloxamer / Q000737:chemistry*; D053838:Scattering, Small Angle; D012980:Sodium Salicylate / Q000737:chemistry; D013050:Spectrometry, Fluorescence / Q000379:methods*; D047392:beta-Cyclodextrins / Q000737:chemistry*
D008823:Micelles; D047392:beta-Cyclodextrins; D020442:Poloxamer; D009288:Naproxen; D008012:Lidocaine; D010424:Pentobarbital; D012980:Sodium Salicylate