Polymer-grafted hollow mesoporous silica nanoparticles integrated with microneedle patches for glucose-responsive drug delivery

doi:10.1007/s11706-021-0532-1

Front. Mater. Sci.

2021, Vol. 15

Issue (1) : 98-112 https://doi.org/10.1007/s11706-021-0532-1

RESEARCH ARTICLE

Polymer-grafted hollow mesoporous silica nanoparticles integrated with microneedle patches for glucose-responsive drug delivery

Yaping WANG¹, Songyue CHENG¹, Wei HU¹, Xue LIN¹, Cong CAO¹, Shufen ZOU², Zaizai TONG¹(

), Guohua JIANG¹, Xiangdong KONG¹

¹. College of Materials Science and Engineering & Institute of Smart Biomedical Materials & Zhejiang-Mauritius Joint Research Center for Biomaterials and Tissue Engineering, Zhejiang Sci-Tech University, Hangzhou 310018, China
². Jiangxi Province Key Laboratory of Polymer Micro/Nano Manufacturing and Devices, School of Chemistry, Biology and Materials Science, East China University of Technology, Nanchang 330013, China

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Abstract

A glucose-mediated drug delivery system would be highly satisfactory for diabetes diagnosis since it can intelligently release drug based on blood glucose levels. Herein, a glucose-responsive drug delivery system by integrating glucose-responsive poly(3-acrylamidophenylboronic acid) (PAPBA) functionalized hollow mesoporous silica nanoparticles (HMSNs) with transcutaneous microneedles (MNs) has been designed. The grafted PAPBA serves as gatekeeper to prevent drug release from HMSNs at normoglycemic levels. In contrast, faster drug release is detected at a typical hyperglycemic level, which is due to the change of hydrophilicity of PAPBA at high glucose concentration. After transdermal administration to diabetic rats, an effective hypoglycemic effect is achieved compared with that of subcutaneous injection. These observations indicate that the designed glucose-responsive drug delivery system has a potential application in diabetes treatment.

Keywords hollow mesoporous silica nanoparticles transdermal delivery diabetes glucose-responsive release microneedles

Corresponding Author(s): Zaizai TONG

Online First Date: 03 February 2021 Issue Date: 11 March 2021

Cite this article:

Yaping WANG,Songyue CHENG,Wei HU, et al. Polymer-grafted hollow mesoporous silica nanoparticles integrated with microneedle patches for glucose-responsive drug delivery[J]. Front. Mater. Sci., 2021, 15(1): 98-112.

URL:

https://academic.hep.com.cn/foms/EN/10.1007/s11706-021-0532-1
https://academic.hep.com.cn/foms/EN/Y2021/V15/I1/98

Fig.1 Scheme 1 Schematic of the glucose-responsive HMSNs-PAPBA integrated with MN patches for the glucose-responsive transdermal delivery of metformin.

Fig.2 Characterization of HMSNs: (a) TEM image of HMSNs; (b) nitrogen adsorption isotherm of HMSNs; (c) pore size distribution of HMSNs.

Fig.3 TEM images of (a) HMSNs-NH₂ and (b) HMSNs-PAPBA. (c)ζ-Potential values of HMSNs, HMSNs-NH₂ and HMSNs-PAPBA in water. (d) FTIR spectra of HMSNs, HMSNs-NH₂ and HMSNs-PAPBA. (e) TGA curves of PAPBA polymer (weight loss: 62.6%), HMSNs (weight loss: 12.4%) and HMSNs-PAPBA (weight loss: 22.2%).

Fig.4 (a) In vitro release profiles of metformin from HMSNs-PAPBA nanocarrier under different concentrations of glucose. (b) Cell viability tests of Met@HMSNs-PAPBA against 3T3-L1 cell with different concentrations.

Fig.5 (a) Force–displacement curve of Met@HMSNs-PAPBA MNs. (b) Digital microscopy image of Met@HMSNs-PAPBA MNs after compression by a 150 g weight for 5 min.

Fig.6 Confocal micrographs of R6G-loaded MNs after insertion into the skin for (a) 5 min and (b) 30 min with corresponding 3D reconstruction images.

Fig.7 Confocal laser scanning microscopy images of histological sections of (a) the healthy SD rat skin and (b) the diabetic SD rat skin after the application of R6G-loaded HMSNs-PAPBA MNs for 5 and 30 min.

Fig.8 Time-dependent BGLs after application of different kinds of MNs or injection of metformin into diabetic rats (the diabetic rat sample without any treatment is used as a control) (n = 3).

Scheme S1 The synthetic route of APBA.

Fig. S1¹H-NMR spectrum of APBA in DMSO-d6.

Scheme S2 The synthetic route of PAPBA.

Fig. S2 GPC curve of PAPBA.

Fig. S3¹H-NMR spectrum of PAPBA.

Scheme S3 Scheme of stimuli-responsive PBA groups with glucose.

Fig. S4 Characterization of the prepared MNs: digital microscopy images of Met@HMSNs-PAPBA MNs under (a) low and (b) high magnifications; SEM images of Met@HMSNs-PAPBA MNs from vertical views at (c) low and (d) high magnifications, and from side elevation at (e) low and (f) high magnifications.

Fig. S5 Skin recovery ability test of MNs: (a) before piercing of MNs into the skin; (b) piercing of MNs; (c) removing MNs from the skin for 0 min; (d) after removing MNs from the skin for 10 min.

Fig. S6 TEM images of HMSNs-PAPBA for different degradation intervals in PBS at 37 °C.

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