On-Demand Drug Delivery Systems Using Nanofibers

Abstract

On-demand drug-delivery systems using nanofibers are extensively applicable for customized drug release based on target location and timing to achieve the desired therapeutic effects. A nanofiber formulation is typically created for a certain medication and changing the drug may have a significant impact on the release kinetics from the same delivery system. Nanofibers have several distinguishing features and properties, including the ease with which they may be manufactured, the variety of materials appropriate for processing into fibers, a large surface area, and a complex pore structure. Nanofibers with effective drug-loading capabilities, controllable release, and high stability have gained the interest of researchers owing to their potential applications in on-demand drug delivery systems. Based on their composition and drug-release characteristics, we review the numerous types of nanofibers from the most recent accessible studies. Nanofibers are classified based on their mechanism of drug release, as well as their structure and content. To achieve controlled drug release, a suitable polymer, large surface-to-volume ratio, and high porosity of the nanofiber mesh are necessary. The properties of nanofibers for modified drug release are categorized here as protracted, stimulus-activated, and biphasic. Swellable or degradable polymers are commonly utilized to alter drug release. In addition to the polymer used, the process and ambient conditions can have considerable impacts on the release characteristics of the nanofibers. The formulation of nanofibers is highly complicated and depends on many variables; nevertheless, numerous options are available to accomplish the desired nanofiber drug-release characteristics.

Keywords: drug administration; drug loading; electrospinning; nanofibers; on-demand drug release; polymers.

Figure 1

Schematic of on-demand drug delivery systems using stimuli-responsive NFs.

Figure 2

Schematic of preparation of (a) blended NFs using electrospinning, (b) core-shell NFs using coaxial electrospinning, and (c) layer-by-layer assembly as DDSs.

Figure 3

(a) Preparation of thermally crosslinkable temperature-responsive NFs by blended electrospinning technique. Scanning electron microscopy (SEM) images of DOX/MNP NFs (31 wt% of MNPs and 0.18 wt% of DOX) (b) before and (c) after crosslinking (scale bars are 1 μm). Reproduced with permission from [51], Copyright © 2021, John Wiley & Sons, Inc.

Figure 4

Core–shell NFs for sequential drug delivery of HCPT and TP. Reproduced with permission from [57], Copyright © 2021, American Chemical Society.

Figure 5

Layer-by-layer assembly of core-shell NFs for controlled co-delivery of growth factors for bone tissue engineering. Reproduced with permission from [66], Copyright © 2021, American Chemical Society.

Figure 6

Schematic of various methods of drug loading.

Figure 7

SEM photographs of CipHCl loaded electrospun nanofibers (a) PVA, (b) PVAc, and (c) 50:50 blend of PVA/PVAc. Effect of CipHCl on (d) the diameter of nanofibers and (e) the solution viscosity. Reproduced with permission from [68], Copyright © 2021 Jannesari et al., publisher and licensee Dove Medical Press Ltd., Macclesfield, United Kingdom.

Figure 8

Schematic overview of preparing NGF–conjugated aligned nanofibers to differentiate rMSCs into neuron cells. Reproduced with permission from [71], Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd., Amsterdam, The Netherlands.

Figure 9

(a) Confocal microscopy images using ×63 objective of rhodamine-modified chitosan fiber network (red) with FGF-2^LB/PCN complexes adsorbed (green). (b,c) Confocal microscopy images (using ×20 objective) of FGF-2^LB/PCN fibers and FGF-2^LB/PCN + PEM fibers after 30 days of release at 37 °C. (e,f,h,i) Representative fluorescence microscopy images of MSCs stained with DAPI (nuclei) and calcein-AM (cytoplasm). (d–f) Cells cultured on TCPS coated with chitosan, PCNs (or FGF-2/PCN complexes), one bilayer of TMC–heparin PEM, and fibronectin. (g–i) Cells cultured on fibronectin-coated TCPS with PCNs (or FGF-2/PCN complexes) delivered in solution. § in (d) indicates statistically different results for the two conditions. * in (g) indicates that the FGF-2/PCN-complexes preconditioned for 1, 18, and 27 days in solution result in cell densities that are statistically different from all other conditions in both (d) and (g) that correspond to the same preconditioning time (n = 3, p < 0.05). Reproduced with permission from [78], Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd., Amsterdam, The Netherlands.

Figure 10

(a) Schematic hypothesis of T_g−triggered OCT release from NFs. (b) In vitro pulsewise drug release from NFs. Reproduced with permission from [90], CC BY−NC−ND license, Copyright © 2021 The Authors, Published by American Chemical Society.

Figure 11

Schematic of (a) heat generated by GNRs upon NIR irradiation, (b) NFs encapsulating drug and GNRs after electrospinning, and (c) drug release due to shrinkage of NFs upon NIR irradiation. (d) Pulsatile drug release from NFs through the cyclic on–off of NIR light irradiation at different time intervals. (e) Cell viability of U87 cells due to CPT release from the NFs upon NIR irradiation at different time intervals. Reproduced with permission from [80], CC BY license, Copyright © 2021 The Authors, Published by MDPI. * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001.

Figure 12

Schematic of (a) electrospinning of rGO-loaded PAA NF mats followed by (b) loading with different antibiotics and photothermal triggered antibiotic release. Reproduced with permission from [91], Copyright © 2021, American Chemical Society.

Figure 13

(a) Antibacterial activity of PVA/PAA10*-C samples against S. aureus and E. coli and inhibition zone of PVA/PAA10*-C samples against (b) E. coli and (c) S. aureus. Reproduced with permission from [96], Copyright © 2021, Elsevier.

Figure 14

Strategic underpinning nanoplatform design of pH-responsive NFs allowing MRI monitoring of drug release. Reproduced with permission from [101], CC BY license, Copyright © 2021, The Royal Society of Chemistry.

Figure 15

Variations in electrical conductivity of nanofibers depending on (a) content of oxyfluorinated MWCNTs and (b) oxyfluorination condition for MWCNTs. Reproduced with permission from [102], Copyright © 2021, Elsevier.

Figure 16

(a) Heating and cooling profile of the MET-MET@MSNs-MNFs in response to alternating switching of AMF (b) ‘ON-OFF’ switchable and reversible heat profile and swelling ratio of the MNFs with increasing ‘ON-OFF’ switching cycle of AMF, and MET release pattern corresponding to reversible swell-shrink property in response to temperature changes. Reproduced with permission from [103], Copyright © 2021, Elsevier.

Figure 17

(a) Schematic of the fabrication procedure of the PDA modified PCL-DOX nanofibrous mat. (b) Schematic of cell death mechanism. Reproduced with permission from [94], CC BY license, Copyright © 2021 The Authors, Published by Springer Nature.

Figure 18

(a) Schematic of the inclusion complex formation between ibuprofen and HPβCyD molecules and electrospinning of HPβCyD/ibuprofen-IC NFs. Photographs of electrospinning solutions and the resulting electrospun nanofibrous webs and representative SEM images: (b) pure HPβCyD NFs, (c) HPβCyD/ibuprofen-IC NFs (1:1), and (d) HPβCyD/ibuprofen-IC (2:1) NFs. Reproduced with permission from [112], Copyright © 2021, American Chemical Society.

Figure 19

Schematic of preparation and anti-adhesion of HCPT and DS co-loaded NFs for implantation. Reproduced with permission from [116], Copyright © 2021, American Chemical Society.

Figure 20

(a) Fabrication process of CSLD-PCLM NF scaffolds. (b) Wound healing effect of CSLD-PCLM NF scaffolds in a full-thickness skin defect model. Reproduced with permission from [118], Copyright © 2021, American Chemical Society.