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Philipps-Universität Marburg
Supervisors
Abstract
Dermal drug delivery is a preferred administration route for bypassing first-
pass metabolism, minimizing systemic side effects and delivering local or system ic
benefits. Formulation strategies are often employed to improve drug solubility and
penetration, enhancing dermal bioavailability. Many dermal drugs face solubility
challenges, necessitating advanced formulation strategies. Curcumin is a natural
bioactive compound derived from the turmeric plant Curcum a longa L., and has been
widely used due to its therapeutic benefits against dermal conditions. However, it is
characterized by low solubility and bioavailability. Therefore, dermal curcumin
formulation strategies are often employed to improve its limitations. The established
ex vivo porcine ear model has been frequently used to test various formulations,
providing insights into effective strategies that preserve skin physiology, improve
penetration and elucidate penetration mechanism. Expanding on previous findings, a
systemic study of different classic and novel formulation strategies is necessary to
evaluate their effectiveness in enhancing dermal delivery of poorly water-soluble
drugs. In this context, plant-based extracellular vesicles, plantCrystals, and
microemulsion formulations were selected to be investigated to improve the solubility
and bio-efficacy of a poorly water-soluble drug, curcumin.
The first project studied the impact of classical plant-derived extracellular
vesicles (EVs) and plantCrystals-extracellular vesicles (PCEVs) on curcumin dermal
delivery using an ex vivo porcine ear skin model. Two study designs were employed,
aiming to determine the dermatokinetics of curcumin penetration, and to investigate
penetration efficacy and depth. EVs were isolated through classical methods, while
PCEVs were prepared via bead milling, with curcumin incorporated either during or
after PCEVs formation, resulting in curcumin-loaded and curcumin-added PCEVs,
respectively. Dermatokinetics indicated that curcumin particles facilitated penetration
through a particle-assisted mechanism. Upon evaporation of the dispersion medium,
an aqueous meniscus formed between the particles and skin, creating a high local
concentration gradient that enhanced drug delivery. This effect was most pronounced
in curcumin-loaded PCEVs, where smaller and more abundant particles maximized
the contact area. Curcumin-loaded PCEVs achieved a significantly higher penetration efficacy compared to curcumin-added PCEVs and curcumin-loaded EVs. Its also
exhibited greatest penetration depth, whereas curcumin delivered from EVs remained
in the stratum corneum. The data revealed that incorporating curcumin during PCEVs
production is critical for maximizing penetration efficacy. The findings of this project
confirm the promise of PCEVs as an effective delivery system for curcumin and similar
poorly soluble compounds, highlighting bead milling as a superior strategy over
classical EVs methods. This formulation presented a plant-based and nontoxic
approach as a carrier for dermal drug delivery, thereby it offers a great potential for
pharmaceutical development and further exploration of different potential plants to
improve the solubility and bioavailability of poorly water-soluble drugs.
The second project studied microemulsions as a nano-scaled systems for
improving curcumin dermal delivery using the ex vivo porcine ear model. The study
investigated how microemulsion components and their varying concentration s
influence the penetration efficacy. Nine of curcumin microemulsion formulations
were prepared with varying ratios of the oily and water phases and the surfactants
mixture (surfactant and co-surfactant (Smix)). Formulations with higher oily phase
content exhibited larger hydrodynamic sizes and broader size distribution, while
those with higher Smix and water content demonstrated smaller sizes and narrower
size distribution. Results showed enhanced penetration efficacy of curcumin was
associated with higher ethanol and water ratios. This highlights the role of
composition in modulating curcumin transport through the skin. Bench controls,
including curcumin solutions and dispersion were prepared to elucidate the vehicle
effect on curcumin delivery. Based on the data obtained, it can be assumed that the
curcumin penetration from microemulsion formulations revealed overlappin g
penetration mechanisms influenced by the formulation’s composition. While
microemulsion formulations effectively delivered curcumin to the upper epiderm is,
their limited penetration depth restricts their use for targeting the dermis. These
findings provide a foundation for optimizing microemulsion systems to enhance the
dermal delivery of poorly soluble active compounds like curcumin.
Review
Metadata
Contributors
Supervisor:
Dates
Created: 2025Issued: 2025-12-01Updated: 2025-07-09
Faculty
Fachbereich Pharmazie
Publisher
Philipps-Universität Marburg
Language
eng
Data types
DoctoralThesis
Keywords
plantCrystalsex vivo porcine ear modelextracellular vesiclesDermal drug deliveryextracellular vesiclesplantCrystalsDermal drug deliverymicroemulsionsmicroemulsionsex vivo porcine ear model
DFG-subjects
microemulsionsex vivo porcine ear modelDermal drug deliveryplantCrystalsextracellular vesicles
DDC-Numbers
500
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Alkhaldi, Muzn: Novel Formulation Strategies for Improved Dermal Delivery of Curcumin. : Philipps-Universität Marburg 2025-12-01. DOI: https://doi.org/10.17192/z2025.0495.
License
This item has been published with the following license: In Copyright