In Situ Formation of Polymer Matrices for Localized Drug Delivery

As a widely used anticancer drug, doxorubicin (DOX) could induce cell death mainly via interfering with DNA activity; thus, DOX could perform therapeutic effects mainly in the cell nucleus. However, most of the reported drug delivery systems lacked the well localization in the nucleus and released DOX molecules into the cytoplasm. Due to formidable barriers formed in the nuclear envelope, only around 1% of DOX could reach the nucleus and keep active. Therefore, DOX molecules were inevitably overloaded to achieve the desired therapeutic efficacy, which would induce serious side effects. Herein, we developed a highly localized drug nanocarrier for in situ release of DOX molecules to their action site where they could directly interfere with the DNA activity. In this work, we used cationic polymer-modified upconversion nanoparticles (UCNPs) as the luminescence core and gene carrier, while aptamers served as the DNA nanotrain to load DOX. Finally, the prepared nanotheranostic agent displayed good targetability, high cell apoptosis ratio (93.04%) with quite lower concentration than the LC50 of DOX, and obvious inhibition on tumor growth.

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MMP-8-Responsive Polyethylene Glycol Hydrogel for Intraoral Drug Delivery

Journal of Dental Research ◽

10.1177/0022034519831931 ◽

2019 ◽

Vol 98 (5) ◽

pp. 564-571 ◽

Cited By ~ 9

Author(s):

J. Guo ◽

H. Sun ◽

W. Lei ◽

Y. Tang ◽

S. Hong ◽

...

Keyword(s):

Drug Delivery ◽

Polyethylene Glycol ◽

High Performance ◽

Oral Diseases ◽

On Demand ◽

Michael Type Addition ◽

Minocycline Hydrochloride ◽

Environmentally Sensitive ◽

Localized Drug Delivery

Currently available drug delivery systems for oral diseases suffer from short retention time and poor local concentrations at the target site. A biodegradable stimulus-responsive hydrogel was synthesized in the present study to evaluate its application as an environmentally sensitive carrier for on-demand intraoral drug delivery. The hydrogel was synthesized from diacrylate-containing polyethylene glycol–based scaffolds and a cysteine-terminated peptide crosslinker (CGPQG↓IWGQC) via a Michael-type addition reaction. Because CGPQG↓IWGQC can be cleaved by matrix metalloproteinase 8 (MMP-8), minocycline hydrochloride, bovine serum albumin, or an antibacterial peptide (KSL) was incorporated into the scaffolds to evaluate the MMP-8-responsive release behavior of the on-demand drug delivery system. Hydrogel characterization and gelation kinetics were examined with gel time, Fourier-transform infrared spectroscopy, scanning electron microscopy, and measurements of rheologic parameters. Degradation behavior and MMP-8-responsive drug release were performed by high-performance liquid chromatography and protein-specific assay. Biocompatibility evaluation indicated that the hydrogels were noncytotoxic. Antibacterial testing demonstrated that the released drugs were able to maintain bioactivity. Taken together, these results suggest that the MMP-8-sensitive hydrogel is a promising candidate for on-demand intraoral localized drug delivery. Because MMP-8 is one of the most important biomarkers for periodontitis, the MMP-8-responsive hydrogel has potential to be used for in situ adaptive degradation in response to chronic periodontitis and peri-implantitis. This notion has to be tested in animal models of periodontal disease.

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