Growth, Shrinking, and Breaking of Pluronic Micelles in the Presence of Drugs and/or β-Cyclodextrin, a Study by Small-Angle Neutron Scattering and Fluorescence Spectroscopy

Abstract

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.

Poloxamer-based binary hydrogels for delivering tramadol hydrochloride: sol-gel transition studies, dissolution-release kinetics, in vitro toxicity, and pharmacological evaluation

“…The interactions between lidocaine, naproxen, salicylic acid, or pentobarbital with PL 407 micelles were also studied by other authors, 29 showing that the presence of charge on the incorporated molecule chemical structure influences the partitioning into submit your manuscript | www.dovepress.com…”

Rupture of Pluronic Micelles by Di-Methylated β-Cyclodextrin Is Not Due to Polypseudorotaxane Formation

“…At these concentrations (5% F127/9% DIMEB), it is known from SANS experiments that the micelles are fully broken. 17 The absorbance spectrum of MO just after mixing ( Figure 1A (4)) appears slightly shifted compared to that of F127 and DIMEB and with a higher absorbance, reflecting changes in the system. Over the 17 h of measurement, no further modification of the spectrum was observed; thus, the shift and the increase in absorbance reflect very rapid structural changes taking place between the mixing event and the first scan, which can be estimated to be ∼45 s. The spectrum can be deconvoluted into three Gaussians (Table 1, Supporting Information Figure SI 2); two of them correspond to the absorbance maxima of MO in DIMEB and (a very small proportion of) MO in water.…”

Drug-Induced Morphology Switch in Drug Delivery Systems Based on Poly(2-oxazoline)s

“…Changes in the aggregation behavior of amphiphilic polymers upon drug incorporation have been previously reported for pluronic and other systems. 29−32 Depending on the nature of the drug, the micelles increased 29 or decreased 30 in size. More interestingly, drugs also induced sphere-to-rod transitions, where the incorporated drug shifted the balance from spherical toward wormlike micelles.…”