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Temperature and Ultrasound Sensitive Gatekeepers for the Controlled Release of Chemotherapeutic Drugs from Mesoporous Silica Nanoparticles


With the advent of smart biomaterials, environmental stimuli have always been the trigger for targeted drug delivery. Conventional routes of drug administration suffer from serious drawbacks like first pass metabolism, less patient compliance and aid of trained personals. Of the many well-established non-conventional routes, transdermal drug delivery systems (TDDS) seems to be most promising as it does not enter directly into the bloodstream and hence, side effects can significantly be reduced. Researchers around the world are trying to incorporate environmental sensitivity to TDDS. Herein, we report the design and fabrication of a dual sensitive TDDS: (tetrahydropyranyl methacrylate-co-amino ethyl methacrylate)-grafted-mesoporous silica nanoparticles (THPMA-co-AEMA)-g-MSN that could simultaneously sense temperature and an external stimuli - ultrasound (US). Temperature sensitivity was imparted by the conformational changes adopted by the system above and below lower critical solution temperature (LCST). Below LCST (4 oC), polymer would exist as linear chains allowing drug molecules to enter the mesopores of silica and at physiological temperatures, copolymer collapses preventing premature drug leakage. This sensitivity could be complemented by the inclusion of mechanophores like tetrahydropyran (THP), which could cleave bonds on exposure to US. At physiological temperatures, TDDS can be placed at malignant sites and on US exposure, the chemotherapeutic agents could be leached out, resulting in better targeting, efficient drug release as well as minimum side effects. US can act as potential penetration enhancers that making them ideal even for targeting of internal organs. All reaction procedures were monitored with the aid of FTIR, XRD, 1H NMR and FE-SEM techniques. Temperature sensitivity was analysed by encapsulating with 5-flurouracil (5-FU) and analysing with UV-Visible spectrophotometer. US sensitivity was monitored as a function of scattering light intensity. Pore opening and closure was verified by nitrogen adsorption isotherms. The dual responsiveness of the material was confirmed by confocal images of the sample before and after exposure to US. Physiological acceptance and practical efficacy of the material in real life situations were confirmed by histological studies on rat skin, MTT assay in HeLa cell lines and in vivo CAM assay. Results suggest the potential applicability of the material in site selective transdermal delivery of chemotherapeutic drugs.

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Publication details

The article was received on 28 Aug 2017, accepted on 28 Nov 2017 and first published on 29 Nov 2017

Article type: Paper
DOI: 10.1039/C7TB02292A
Citation: J. Mater. Chem. B, 2017, Accepted Manuscript
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    Temperature and Ultrasound Sensitive Gatekeepers for the Controlled Release of Chemotherapeutic Drugs from Mesoporous Silica Nanoparticles

    T. S. Anirudhan and A. S. Nair, J. Mater. Chem. B, 2017, Accepted Manuscript , DOI: 10.1039/C7TB02292A

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