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Lithography-directed Self-assembly for Designing Drug Particles of Various Sizes and Morphologies

Forghan Tarigheh, Fatemeh | 2025

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  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 57966 (06)
  4. University: Sharif University of Technology
  5. Department: Chemical and Petroleum Engineering
  6. Advisor(s): Safari, Hanieh
  7. Abstract:
  8. To design a drug delivery system, the drug must be encapsulated within a carrier matrix. One of the main challenges in this field is encapsulating high drug doses while achieving a linear release profile at the target site to maintain drug concentration for optimal therapeutic effects. Consequently, many research groups have focused on refining fabrication techniques to maximize loading efficiency and optimize drug release profiles from delivery systems. A potential approach to addressing this issue is the direct fabrication of a controlled-release system from the active pharmaceutical ingredient (API) itself, eliminating the need for a carrier matrix. Studies have demonstrated that such particles can undergo surface erosion, enabling the linear release of the active drug. However, the size of these particles has been restricted to the micron scale, and due to the limitations of self-assembly techniques, reducing their dimensions further to the nanoscale has not been feasible. To utilize these particles for therapeutic applications requiring intravenous or intra-articular administration, particle size must be reduced to prevent embolism and joint obstruction. In this project, we propose that lithographic templates can be used to guide metal-assisted self-assembly for fabricating drug particles with various sizes and shapes. The lithographic template and its wells are intended to constrain particle growth outside the template walls. Additionally, to produce particles within the desired size range, controlled deposition on the self-assembly process was employed by adjusting key parameters within the drug formulation system, yielding promising results. In the second approach, we examined the effects of critical parameters on reducing drug particle size. Among these, two parameters—precursor concentration and reaction medium pH—exhibited the most significant impact on particle size and morphology. Using this method, we successfully fabricated drug particles within the size range of 0.2 µm to 1.7 µm. Results indicated that increasing precursor concentration and pH significantly reduced particle size and altered morphology. These changes can be attributed to an increased nucleation rate under higher concentration and pH conditions. In this state, the supersaturation level of the medium rises, leading to the formation of a greater number of initial nuclei. Consequently, competition among the nuclei limits their individual growth, resulting in smaller particles with more diverse morphologies. This study demonstrates that precise control of process parameters—particularly concentration and pH—is an effective tool for reducing particle size and improving distribution uniformity, enabling the production of nanoparticles with desirable physical properties. Through this project, we determined that the optimal concentration for the concentrated phase of the chelate was 5%, the diluted phase was 0.3%, and the ideal pH range was 10.5 to 10.8. Compared to the lithography-based templating method, controlled deposition proved to be significantly more cost-effective, operationally simpler, and required fewer resources and less complex equipment. Furthermore, this method enabled the production of drug particles through self-assembly, even within the nanometer range, offering a promising approach for enhancing the applicability of various drugs in treating a broader spectrum of diseases
  9. Keywords:
  10. Drug Delivery ; Lithography ; Steroid ; Emboli Detection ; Self Assembly ; Controlled Precipitation ; Deposit Morphology

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