Skip to main navigation Skip to search Skip to main content

Investigation of Transdermal Drug Delivery Systems of Electrospun Nanofibers and Microneedles Utilising Novel Imaging Approaches

  • Rand Abdulhussain

Student thesis: Doctoral Thesis

Abstract

Transdermal route has gained significant interest in recent years and is one of the most investigated approaches in drug delivery. However, the application of transdermal drug delivery systems (TDDS) remains challenging because the skin acts as a barrier that limits the entry of most foreign substances. Electrospinning has emerged as a promising technique in transdermal drug delivery (TDD), as electrospun membranes offer high drug loading and encapsulation efficiency, making them suitable for transdermal patches. In parallel, advances in microneedle technology are enabling the fabrication of minimally invasive systems that enhance drug permeation across the stratum corneum and improve delivery efficiency. Building on these developments, this thesis investigates electrospun nanofibers and dissolving microneedles for transdermal drug delivery, with particular focus on the influence of polymer molecular weight and formulation design on drug release and permeation behaviour. UV imaging was employed to study the relationships between formulation properties, surface characteristics, and drug transport mechanisms across the fabricated systems.The initial phase of the study investigated electrospun nanofiber patches made from polyvinyl alcohol (PVA) and polyethylene oxide (PEO) of varying molecular weights (300, 600, and 900 kDa), with nicotinamide (NIC) as the model drug. Monoaxial electrospinning was used to evaluate the effect of PEO molecular weight on fiber morphology, mechanical properties, drug release, and permeation. Increasing PEO molecular weight resulted in larger fiber diameters, more morphological defects, reduced mechanical strength, and faster drug release and permeation. Among the monoaxial formulations, F3 (PVA‑PEO900 kDa‑NIC) displayed the highest permeation (328.2 ± 48.9 µg/cm² after 8 h), compared with 133.0 ± 36.5 µg/cm² for F1 (PVA‑PEO300 kDa‑NIC). Coaxial electrospun formulations were then developed, consisting of a PVA‑NIC core and a PEO shell of different molecular weights. In contrast to the monoaxial systems, increasing PEO molecular weight in the shell improved mechanical strength and slowed drug permeation. C1 (PVA‑PEO300 kDa‑NIC) demonstrated the highest permeation (186.1 ± 20.9 µg/cm²), while C3 (PVA‑PEO900 kDa‑NIC) showed the lowest (94.5 ± 33.0 µg/cm²). Statistical analysis confirmed significant differences between monoaxial and coaxial systems at all time points (P < 0.05). Kinetic modelling indicated that most formulations followed the Higuchi model, suggesting diffusion through a hydrated polymer matrix as the dominant mechanism, while F3 and C1 followed first‑order kinetics.The study also explored the use of vacuum compression moulding (VCM) to fabricate dissolving microneedles for TDD. PEO of different MWs was used as the backing layer, while a PVA-PEO mixture was used as the base layer. Increasing PEO MW increased surface roughness and contact angle and reduced needle quality due to incomplete mould filling. NIC permeation also decreased with increasing MW, with MN0 (PVA-NIC) showing the highest permeation (916.8 ± 379.5 µg/cm²; 72.7 ± 30.1%) and MN3 (PVA-PEO 300 kDa-NIC) the lowest permeation (536.9 ± 173.8 µg/cm²; 42.6 ± 13.0%) after 8 h, which may be related to the thicker swollen gel layer formed by higher MW PEO and thus lower drug diffusivity within the matrix.Surface roughness analysis and UV imaging provided further insight into the relationship between formulation structure and drug transport. For monoaxial fibers, surface roughness increased from 0.7 ± 0.1 μm (F1) to 4.7 ± 1.8 μm (F3), accompanied by increased wettability (contact angle decreasing from 56o to 26.3o). UV imaging correlated these findings with higher cumulative NIC permeation increasing from 8.7 ± 1.5% (F1) to 25.9 ± 1.9% (F3). Coaxial fibers showed lower variation in surface roughness, which was attributed to a more uniform outer shell that contributed to higher contact angles. For microneedles, surface roughness increased with PEO molecular weight (2.4 ± 0.2 µm for MN0 to 4.4 ± 0.4 µm for MN3). This was attributed to higher viscosity and reduced mould filling. UV imaging indicated that although roughness increased, higher MW reduced chain mobility and hindered NIC release.Overall, this work demonstrates the potential of controlling drug release and permeation by modifying polymer molecular weight and structural design in electrospun fibers and dissolving microneedles. The study also highlights UV imaging as a valuable complementary tool to traditional Franz diffusion cells by providing both qualitative and quantitative insights into formulation behaviour. Collectively, the findings offer a mechanistic understanding of how polymer selection, manufacturing method, and structural design influence drug transport in transdermal delivery systems.
Date of Award3 Sept 2026
Original languageEnglish
SupervisorKofi Asare-Addo (Main Supervisor) & Adeola Adebisi (Co-Supervisor)

Cite this

'