Breaking the barrier - Efficient topical delivery using responsive nanocarriers

2020/02/25 Atrio 800

Seminar

Breaking the barrier - Efficient topical delivery using responsive nanocarriers

Prof. Marcelo Calderón

Breaking the barrier - Efficient topical delivery using responsive nanocarriers The term nanogel (NG) refers to nanometer-sized crosslinked polymeric networks that reveal intrinsic properties ideal for biomedical applications, i.e. high water content, soft nature, cell and tissue compatibility, and excellent water dispersibility/solubility. Therefore, NGs are commonly developed as drug carriers which shrink or swell significantly by expelling or absorbing large amounts of water, selectively releasing their cargo in response to external stimuli. Among such stimuli, temperature is attractive because of its simple accessibility and easy applicability, both in vitro and in a biological environment.1 In this context, our group has developed several thermoresponsive NGs as drug delivery systems based on dendritic polyglycerol as a macro-crosslinker and different thermoresponsive polymers such as poly(N-isopropylacrylamide),2 poly(oligo ethylene glycol methacrylate),3 and thermoresponsive poly(glycidyl ether).4 Their biocompatibility, together with the possibility of fine tuning their size and responsive modality, makes them ideal candidates for various therapeutic and diagnostic approaches, particularly for topical drug delivery. Topical administration permits targeted, sustained delivery of therapeutics to human skin. Delivery to the skin however is limited to lipophilic molecules with molecular weight of typically < 500 Da, capable of crossing the stratum corneum. Nevertheless, there are indications pointing that protein delivery may be possible in barrier deficient skin, a condition found in several inflammatory skin diseases such as psoriasis and atopic dermatitis, and in congenital diseases like autosomal recessive congenital ichthyosis. Here, the synthesis, characterization, and potential application in topical protein delivery of thermoresponsive NGs is presented. The delivery of proteins such a Transglutaminase 1,2b Etanercept,4b and Ovalbumin 5 will be discussed as models for protein replacement therapy, anti inflammatory treatment and needle-free vaccination, respectively. [1] (a) M. Asadian-Birjand et al., Curr. Med. Chem. 2012, 19, 5029-5043; (b) J. Bergueiro, M. Calderón. Macrom. Bioscience 2015, 15, 183-199; (c)M. Molina, M. Calderón et al., Chem. Soc. Rev. 2015, 44, 6161-6186. [2] (a) M. Molina, S. Wedepohl, M. Calderón, Nanoscale 2016, 8, 5852–5856; (b) R. Planck et al., J. Investig. Derm. 2019, 139, 1191-1195. [3] (a) M. Asadian-Birjand et al., Polym. Chem. 2015, 6, 5827-5831; (b) M. Asadian-Birjand et al., Macromol. Bioscience 2016, 1432−1441; (c) F. Rancan, M. Calderón et al., J. Control. Release 2016, 228, 159–169. [4] (a) M. Giulbudagian, M. Calderón et al., Polym. Chem. 2014, 5, 6909-6913; (b) M. Giulbudagian, M. Calderón et al., Theranostics 2018, 8, 450-463; (c) M. Giulbudagian, M. Calderón et al., Nanoscale 2018, 10, 469-479. [5] A.S. Sonzogni, M. Calderón, R. J. Minari et al., Biomacromolecules 2018, 19, 4607–4616.

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