The aim of this study is to characterise, using non-invasive techniques, three-dimensional sponges made of electrospun PLA fibres for its use in controlled drug release applications. This type of sponge is novel, so the fundamental processes that occur inside it concerning the absorption of liquids and their subsequent release are still unknown.
The development of novel and alternative controlled drug delivery systems is a very active area of research in the pharmaceutical industry. Currently, controlled drug delivery is done through preformed implants, microparticles and in-situ formed implants. Problems with these systems include complex manufacturing, undesirable release profiles, autocatalytic degradation of polymers leading to very acidic microenvironments (pH around 2) and, in some cases, the need to inject organic solvents into the body for implant formation.
A challenging alternative is the use of Polymer Fiber Sponges (PFS), which are highly porous three-dimensional scaffolds made from polymer fibers obtained by electrospinning. Electrospinning is a very versatile tool for the creation of scaffolds that allows, from polymeric solutions, to obtain a wide variety of electrospun fibers in which it is possible to adjust their size and distribution, as well as the porosity of the structure. However, they are generally produced in the form of thin two-dimensional (2D) sheets. This results in a structure with a low specific pore volume, requiring larger incisions to place the implants at the treatment site, which is problematic. As an alternative solution, it is proposed to fabricate PFSs by freeze-drying using fibers obtained by electrospinning. This process makes it possible to obtain a three-dimensional (3D) matrix that is compact, stable, with adjustable porosity and interconnected in all directions, all qualities that favor the loading and subsequent release of drugs. In addition, this manufacturing technique allows both the size of the fiber and the size of the sponge itself to be adjusted and can be created from different materials, including degradable polymers.
Drug loading into the sponge can be done either by incorporating the drug into the solution used during electrospinning, so that it forms part of the fibers themselves, or by incorporating it into the pores of the PFS once it has been created. The choice of one method or the other will depend on the nature of the drug itself and the desired release profile.
In PFSs, the parameters that determine their drug retention and release capacity are their permeability and hydrophobicity. However, the fundamental mechanisms that occur within PFSs during these drug loading and release processes are still poorly understood. Therefore, the aim of this scientific publication is to investigate these processes in more detail using non-invasive techniques.
Materials and methods
The characterized PFS was fabricated from PLA (polylactide acid) fibers obtained by electrospinning. To achieve the cylindrical shape, the fibers were formed by cold drying, resulting in a PFS with a density of 12.5 mg/cm3, a height of 6.1 mm and a diameter of 8.0 mm. To adjust the drug release profile, the PFS was coated with PPX (poly(para xylylene)) by chemical vapor deposition (CVD), increasing its final density to 28 mg/cm3.
The non-invasive techniques used to characterize the liquid absorption and subsequent release in the PFS were:
- µCT (micro Computed Tomography) to record 3D images of the distribution of liquid and air inside the PFS during drug loading and release.
- NMR (Nuclear Magnetic Resonance) to study diffusion coefficients.
- EPR (Electron Paramagnetic Resonance) spectroscopy and imaging to record the amount of liquid that the PFS was able to absorb over time.
From a mechanical point of view, the PFSs are able to maintain their shape and elasticity in all tests carried out, both in dry and liquid-loaded conditions. Furthermore, the results show that the PFSs retain liquids within their structure and preserve the drug in a given geometry.
The results also show that the properties of PFSs can be adjusted through the addition of excipients and coatings during their manufacture, so that the desired drug release characteristics can be achieved.
Therefore, PFSs made by electrospinning fibers are shown to be a very versatile support for controlled drug delivery in various applications, such as pharmaceuticals or tissue engineering.
Noninvasive characterization (EPR, μCT, NMR) of 3D PLA electrospun fiber sponges for controlled drug delivery
International Journal of Pharmaceutics: X 2 (2020) 100055