Polymeric microneedle-mediated sustained release systems: Design strategies and promising applications for drug delivery

Abstract

Parenteral sustained release drug formulations, acting as preferable platforms for long-term exposure therapy, have been wildly used in clinical practice. However, most of these delivery systems must be given by hypodermic injection. Therefore, issues including needle-phobic, needle-stick injuries and inappropriate reuse of needles would hamper the further applications of these delivery platforms. Microneedles (MNs) as a potential alternative system for hypodermic needles can benefit from minimally invasive and self-administration. Recently, polymeric microneedle-mediated sustained release systems (MN@SRS) have opened up a new way for treatment of many diseases. Here, we reviewed the recent researches in MN@SRS for transdermal delivery, and summed up its typical design strategies and applications in various diseases therapy, particularly focusing on the applications in contraception, infection, cancer, diabetes, and subcutaneous disease. An overview of the present clinical translation difficulties and future outlook of MN@SRS was also provided.

Keywords: Long-term exposure therapy; Microneedles; Sustained release; Transdermal drug delivery.

Graphical abstract

Fig. 1

Design strategies of polymeric microneedle-mediated sustained release system (A) Long-acting coated MNs, (B) Long-acting encapsulated MNs, (C) Polymeric-based sustained release MNs, (D) Double-sustained release MNs, (E) Back layer-based depot MNs.

Fig. 2

(A) Schematic of rapidly separable microneedle patches, (B) The black arrows identify bubble structures at the interface of the microneedles and patch backing, (C) Cumulative release profile of encapsulated LNG . Copyright 2019, Springer Nature.

Fig. 3

(A) Schematic illustrations for the construction of MNs on a water-soluble backing, (B) Cumulative release of the covalently linked (amide and urea bonds) Dox, compared to the control phyically trapped Dox, (C) Measurement results of the tumor size for 12 d postinoculation . Copyright 2020, American Chemical Society.

Fig. 4

(A) Schematic illustration of MN-based transdermal vaccination, (B) In vitro collective release of tumor lysate proteins from the MN patch, (C) Average tumor volumes in treated mice after tumor challenge . Copyright 2017, The American Association for the Advancement of Science.

Fig. 5

(A) Schematic for the components and application of DNA-coated MNs, (B) SEM images of DNA-coated MNs, (C) DNA release profile from MNs . Copyright 2020, Royal Society of Chemistry.

Fig. 6

(A) Glucose-dependent equilibria of PBA derivatives, (B) Schematic representation of formation of semi-IPN hydrogel, (C) “Skin-layer” controlled glucose-responsive insulin release from the MN-array patch . Copyright 2018, John Wiley and Sons.

Fig. 7

(A) Schematic of silk/PAA MN preparation, (B) Optical image and confocal images of silk/PAA MN array encapsulating AF647-OVA (blue) in silk tips, and AF555-OVA (red) in PAA pedestals, (C) SEM images of silk/PAA MN, (D) OVA release from silk and PAA fractions of composite MNs over time . Copyright 2013, John Wiley and Sons. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 8

(A) Illustration of the antimicrobial MN patch, (B) In vivo fluorescence imaging shows the release of Cy5 from MN at different times, (C) Quantitative in vivo release profiles of Cy5 from MN . Copyright 2019, John Wiley and Sons.