Thesis
Self-assembling silk for cell and drug delivery
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2026
- Thesis identifier
- T18020
- Person Identifier (Local)
- 202253748
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- In the past decade, silk has emerged as a promising biomaterial for biomedical and pharmaceutical applications, ranging from biomedical textiles to bioinspired drug-delivery nanoparticles with enhanced functionality. Although silk is widely regarded as a sustainable material, the translation of silk nanoparticles to industrial-scale applications remains challenging due to inconsistent production yields, scale-up limitations in manufacturing, and drug loading and delivery inefficiencies. Notably, silkworms possess a remarkable ability to spin silk fibers under physiological conditions by precisely regulating silk structural and conformational properties through various intrinsic and extrinsic factors, particularly metal ions. Thus, the central hypothesis of this thesis is that biomimicking the silkworm spinning mechanism may provide valuable insights into optimizing processing parameters to produce high-performance silk biomaterials while minimizing material waste during laboratory-scale silk nanoparticle manufacture. To test this hypothesis, silk nanoparticles were manufactured using the antisolvent precipitation method in semi-batch format. Calcium ions (Ca²⁺), a major ion present in the silk gland, were initially selected to optimize nanoparticle functionality and improve production yield. Spiking liquid silk with Ca²⁺ enhanced silk-silk interaction and self-assembly in a semibatch format, resulting in a tunable nanoparticle size along with increased production yield. This optimized process also ultimately produced high biocompatible silk nanoparticles, as the resulting silk nanoparticles showed no toxicity and immunogenicity on the immune cell model, a RAW 264.7 murine macrophage (Chapter 2) (Roamcharern, N., et al., ACS Biomater Sci Eng, 2025, 11(3), 1847-1856). To expand the understanding of metal ion modulation and its impact on silk nanoparticle fabrication via the antisolvent precipitation method, potassium ions (K⁺) were investigated in parallel with calcium ions (Ca²⁺). It was hypothesized that monovalent and divalent ions exert distinct effects on silk-silk interactions and/or self-assembly during nanoparticle formation, thereby yielding silk nanoparticles with distinct physicochemical properties. The findings demonstrated that K⁺ and Ca²⁺ exerted coordinated effects on particle size, shape, and loading efficiency (Thioflavin T encapsulation), suggesting complementary underlying mechanisms. However, Ca²⁺ showed a greater impact on aqueous silk fibroin behavior than that of K⁺, as evidenced by the Thioflavin T assay and NMR analysis, resulting in larger particle size and higher yield (Chapter 3) (Roamcharern, N., et al., ACS Applied Bio Materials, 2025, 8(8), 6854-6864). The physicochemical stability of nanoparticles typically limits their therapeutic applications, as loss of physical stability, particularly colloidal stability, can negatively affect biologically relevant properties in vivo, thereby triggering immunogenic responses and reducing circulation time. This chapter hypothesizes that the incorporation of counterions improves the physicochemical stability of silk nanoparticles. To test this hypothesis, both short term (2 h) and long-term (56 days) stability studies were conducted under various dispersants, pH conditions, and temperatures. Silk nanoparticles were characterized using complementary analytical techniques to assess their physicochemical stability, including DLS, ELS, NTA, SEM, AF4, and EAF4. The findings revealed that Ca²⁺ and K⁺ enhance the colloidal stability of silk nanoparticles during storage, particularly under elevated temperature and ionic stress conditions, thereby demonstrating their potential for drug delivery applications (Chapter 4) (Roamcharern, N., et al., Nanoscale Adv, 2025, 7(18), 5519-5535). To enhance the suitability of silk nanoparticles for drug delivery, a Ca²⁺- and K⁺-free formulation was selected as a prototype for doxorubicin incorporation. Drug-loading efficiency was compared between direct antisolvent precipitation and post-fabrication adsorption, and release kinetics were evaluated under physiological, tumor microenvironment, and lysosomal pH conditions. The results demonstrated that the encapsulation method significantly influences physicochemical properties and pH-responsive drug release, with the adsorption-based formulation showing greater in vitro release. Moreover, compared to free doxorubicin, drugloaded silk nanoparticles exhibited improved biocompatibility toward RAW 264.7 murine macrophages and enhanced selectivity against MDA-MB-231 and DU145 cancer cells. Collectively, these findings support the rational design of tunable silk-based nanocarriers for targeted doxorubicin delivery and establish a versatile manufacturing pipeline applicable to Ca²⁺- and K⁺-mediated silk nanoparticles (Chapter 5). Overall, this thesis established the roles of Ca²⁺ and K⁺ in silk nanoparticle fabrication via the antisolvent precipitation method, along with a physicochemical and systematic evaluation pipeline using orthogonal analytical techniques (Chapter 6).
- Advisor / supervisor
- Rattray, Zahra
- Faulds, Karen
- Resource Type
- DOI
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PDF of thesis T18020 | 2026-07-15 | Public | Download |