Abstract
Hyaluronate (HA) has been widely investigated for noninvasive topical drug delivery of chemical drugs and biopharmaceuticals. However, previous noninvasive delivery systems have been facilitated mostly by chemical conjugation of drugs with HA, which can cause reduced therapeutic efficacy and safety issues in chemically modified drugs. Here, HA nanogels were synthesized by crosslinking via “click” chemistry for noninvasive topical delivery of a model drug without chemical modification. The model-drug-encapsulating HA nanogels could be uptaken to the skin melanoma cells in vitro by HA-mediated endocytosis. In addition, histological analysis showed that HA nanogels could be topically delivered to the deep skin and tongue tissues through the noninvasive delivery routes. Taken together, HA nanogels could be effectively used for the noninvasive topical delivery of various therapeutic drugs.
Highlights
A variety of noninvasive drug-delivery systems, such as oral, pulmonary, ocular, nasal and transdermal delivery, have been presented as attractive alternatives to needle-based drug delivery with great patient compliance [1,2,3,4,5]
The HA nanogels were synthesized by bioorthogonal reaction of Cu-free click chemistry between Tz and TCO
In order to confirm the feasibility of HA nanogels as a noninvasive drug delivery carrier, we investigated in vitro release profile of a fluorescent model drug of fluorescein isothiocyanate (FITC) for 48 h by UV-vis spectroscopy (Figure 3)
Summary
A variety of noninvasive drug-delivery systems, such as oral, pulmonary, ocular, nasal and transdermal delivery, have been presented as attractive alternatives to needle-based drug delivery with great patient compliance [1,2,3,4,5]. Needle-free topical delivery without involving physical damage to the natural skin barrier is greatly advantageous, as it can further resolve compliance issues, such as needle-induced anxiety, and is convenient for drug delivery This long-standing goal has continued to exist, since the skin barrier prohibits the penetration of most large and hydrophilic drug molecules, such as proteins, peptides and nucleotides [9,10,11]. With enhanced penetration into the skin, the HA conjugate showed a proliferative effect on keratinocyte and fibroblast, with an elevated expression level of phosphorylated Janus kinase 2 (p-JAK2) Since this delivery requires chemical conjugation between the drug and carrier molecules, the drugs, especially biopharmaceuticals, can be denatured, and their therapeutic efficacy reduced by the chemical modification
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