3d hierarchical nanofiber scaffolds by needless electrospinning for drug delivery applications / Ramprasath Ramakrishnan

College of Engineering

Thesis (Doctor of Philosophy) -- Universiti Malaysia Pahang – 2021

Includes bibliographical references

Nanofiber scaffolds plays a significant role in targeted drug delivery applications. Traditionally the nanofibers are produced from polymer solution by applying a high voltage between the needle tip and the collector ground surface and the process is called electrospinning. However, needle-based electrospinning has a major drawback on mass production and to maintain the reproducibility. This issue was addressed using needleless electrospinning in this study. However, the effect of polymer solution properties and regulated drug release by nanofiber from needleless electrospinning has not yet been completely understood, hence this is the aims of this research. In addition, the biological effect on breast cancer cell lines of the drug loaded nanofiber is also studied. Organic biopolymer such as poly ethylene oxide (PEO), poly (lactic acid) (PLA) and poly caprolactone (PCL) are used in this work to produce the nanofibers scaffold along with the model drug of bovine serum albumin protein (BSA) and titanocene dichloride (Cp2TiCl2) for drug delivery applications. Two types of scaffolds were produced, which is a monolayer PCL nanofiber with drug loaded directly in the polymer solution to study the release of the drug. The second method was multilayer where PCL nanofiber was used as drug containing scaffold with PLA nanofiber acting as a barrier for drug release. The diffusion mechanism was found from the controlled release kinetic study. The study on solution properties shows that PEO solution has a shear thinning property and that a non-conductive PEO polymers can be electrospun to produce a nanofiber with electrolyte addiction. The surface morphology study indicates the produced fibers are less than 200 nm in diameter and amorphous in nature. The results of control release study showed a diffusion release mechanism of drug from a mono layer nanofiber within 48 hrs, while a very small release obtained from the multilayer fiber for similar time period. The two model drugs, i.e. bovine serum albumin protein (BSA) and titanocene dichloride (Cp2TiCl2) was found to be viable in the nanofiber after undergoing a high voltage process. The TEM and SAED pattern shows the materials is amorphous in nature. The FTIR and DSC thermal properties of the nanofibers shows no changes in chemical or thermal properties when compared with previously reported conventional electrospun nanofiber. The biological properties of the PCL-Titanocene dichloride monolayer and multilayer nanofibers were evaluated through the in-vitro cytotoxicity studies using MDA-MB-231 cell lines (Human Breast Adenocarcinoma) and L929 fibroblast cell lines. It was found that the nanofiber doped with Cp2TiCl2 effectively reduce the MDA-MB-231 viability from 93.68% to 57.04%. Flow cytometric analysis confirmed a distinct inhibition of cells at Go/G1 phase in groups treated with nanofiber doped with Cp2TiCl2 with 10.74% apoptotic after 24 h compared to the control cells. This work may serve as a useful guide in understanding the parameters useful for industrial scaleup in developing a nanofiber-based targeted drug delivery scaffold for broader commercial application