1. Smart nanocontainers and nanoreactors
Kyoung Taek Kim, Silvie A. Meeuwissen, Roeland J. M. Nolte and Jan C. M. van Hest*. Nanoscale, 2010, 2, 844–858
Micelles built from stimuli-responsive block copolymers that are sensitive to the pH change in the medium are also of interest. Polymers having a pKa value between 3 and 10 can be adopted as a pH-responsive segment. Bae and coworkers reported on polymeric micelles of poly (L-lactic acid) (PLA)-b-PEG-b-poly(L-histidine) as potential tumour pH-speciﬁc anti-cancer drug carrier. The co-presence of the pH-nonresponsive lipophilic PLA block in the core prevented the micelles from disintegration. Extensive pH-dependent swelling was observed as the size of the micelle increased to 580 nm at pH 6.6 compared to 80 nm at only a slightly higher pH of 7.4. An example in which micelles respond to a larger difference in pH is reported by Xue et al. The hydrophobic drug prednisone acetate was incorporated in micelles constructed from poly(acrylic acid) (PAAc)-b-poly(DL-lactide) (PDLLA) block copolymers. In vitro pH experiments showed only a small drug release at a pH of 1.4, while at pH 7.4 most of the prednisone acetate had diffused into the surrounding solution after 10 h.
2. Structure elucidation and spectroscopic analysis of photodegradants of the anti-rhinitis drug ﬂuticasone furoate
Ben Bardsley,* Marco S. Smitha and Bob H. Gibbon. Org. Biomol. Chem., 2010, 8, 1876–1880
For the peak at RRT 1.20, a molecular ion was obtained consistent with a molecular formula of C27H29F2O6S(Table1), representing a loss of HF relative to ﬂuticasone furoate. In addition, deuterium exchange mass spectrometry showed, in this case, no exchangeable protons in the molecule thus suggesting a change had occurred in the 11-hydroxyl group.MS/MS data were once again inconclusive in pointing to any speciﬁc structure and NMR analysis was required for elucidation. Previous studies of systems such as prednisone and prednisone acetate, have shown that a rearrangement of the cyclohexadienone functionality occurs on exposure to light (Scheme 3a). In addition, the products of these rearrangements, known as the ‘lumi’ products, have also been shown to eliminate HF when there is a ﬂuorine present at C-6 (Scheme 3b). As ﬂuticasone furoate possesses a ﬂuorine at C-6, it was therefore possible that a similar ‘lumi’ rearrangement followed by loss of HF may have occurred. Such an outcomewould be consistent with the mass spectral data obtained on the peaks with RRT 1.04 and 1.20. 1H NMR analysis showed signiﬁcant differences between the spectra of the two impurities and the spectrum of ﬂuticasone furoate suggesting signiﬁcant structural differences potentially consistent with this type of change.
3. Covalently cross-linked amphiphilic block copolymer micelles
Cornelus F. van Nostrum*. Soft Matter, 2011, 7, 3246–3259
A second type of micelles with a thermoresponsive core of pNIPAM and a cross-linked shell (composed of polylysine) was later described by Li et al. Those micelles were cross-linked by glutaraldehyde. Also in this case prednisone acetate was used as the drug and similar release rates as mentioned above were observed in the shrunk and swollen state of the micelles at temperatures above and below the LCST, respectively, and were slightly dependent on the degree of cross-linking.