Electrospun nanofibres in drug delivery: advances in controlled release strategies

Emerging drug-delivery systems demand a controlled or programmable or sustained release of drug molecules to improve therapeutic efficacy and patient compliance. Such systems have been heavily investigated as they offer safe, accurate, and quality treatment for numerous diseases. Amongst newly developed drug-delivery systems, electrospun nanofibres have emerged as promising drug excipients and are coming up as promising biomaterials. The inimitable characteristics of electrospun nanofibres in terms of their high surface-to-volume ratio, high porosity, easy drug encapsulation, and programmable release make them an astounding drug-delivery vehicle.

Excerpt from the article and chapter 4:

4. Drug-encapsulation and controlled-release strategies

A fine understanding of the structure–function relationship is a key to design a customized drug-delivery system.⁴¹ The drug–polymer arrangement inside the nanofibre can be directly related to the drug-release kinetics. Fig. 3 demonstrates the techniques employed for fabricating drug-loaded nanofibres.

The details of the pre- and post-electrospinning strategies to encapsulate the drug into the polymeric matrix and the understanding of its release behaviour are disseminated in the following section.

4.1. During electrospinning

4.1.1. Blend or solution electrospinning

Solution electrospinning is a commonly followed technique in which the drug is first dissolved (Fig. 3(a1)) or dispersed (Fig. 3(a2)) into the polymer solution and then electrospun.⁴⁴ The physico-chemical and mechanical properties of nanofibres are defined by both the drug and polymer. However, meeting the equilibria between the hydrophilic and hydrophobic properties of the drug and polymer is important⁴⁵ because the hydrophobic drug can accumulate on the surface of nanofibres and lead to an isolated release. The disadvantage of blending can be the burst release of the drug in most cases as drug molecules uniformly distributed on the surface of nanofibres diffuse fast. In the case of anti-inflammatory drugs, as the effect needs to be immediate, a rapid release is desired. The disadvantage of blending can be a loss of the activity of the biomolecules due to their sensitivity to organic solvents.

4.1.2. Co-axial electrospinning

The advent of co-axial electrospinning has contributed to reducing the initial burst release and introducing multiple drug releases. In the core and shell set-up, the core-side polymer generally carries the drug that has to be delivered slowly in a prolonged manner. The shell-side polymer is with or without drugs and specifically alters the drug diffusion (Fig. 3(b)). The shell-side polymer always protects the therapeutic agent inside the core from direct contact with the biological environment to avoid its degradation. Core and shell nanofibres enable the encapsulation of sensitive elements, such as proteins, growth factors, antibiotics, and other biologically active molecules.

In recent approaches, Shihao Wen et al. (2019) successfully tuned the release of the dual drugs flurbiprofen and vancomycin for 9 and 17 days, respectively, by using a core–shell nanofibrous assembly.⁴⁶ The anti-inflammatory, hydrophobic drug flurbiprofen was incorporated into the hydrophilic PEO polymer and placed in the shell side, while the anti-microbial drug vancomycin was incorporated into PEO/silk/collagen blend and occupied the core geometry.

In another study, tri-axial electrospinning was introduced by Liu et al. (2019) to obtain electrospun ferulic acid/gliadin nanofibres.⁴⁷ Two non-electrospinnable solutions were placed in the middle (solvent) and outer layers (dilute CA), while the core solution was made up of electrospinnable ferulic acid/gliadin. After electrospinning, a thin coat of CA was formed over the ferulic acid/gliadin nanofibres. The thickness of the coating was found to determine the ferulic acid release.

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Mrunalini K. Gaydhane, *a Chandra Shekhar Sharma a and Saptarshi Majumdarb, Electrospun nanofibres in drug delivery: advances in controlled release strategies, Cite this: RSC Adv., 2023, 13, 7312, Received 24th September 2022, Accepted 14th December 2022, DOI: 10.1039/d2ra06023j, rsc.li/rsc-advances