Engineering sustained release drug delivery systems for treatment of chronic bone disorders

Abstract

Bone disorders including osteoporosis, rheumatoid arthritis, and osteoarthritis represent significant global health burdens. Current therapeutic approaches are limited by poor bioavailability, rapid systemic clearance, adverse effects, and low patient compliance. Mesoporous silica nanoparticles (MSNs) offer a promising solution through targeted, sustained-release delivery systems that can improve treatment efficacy while minimizing side effects. This thesis describes the development and characterization of MSN-based nanocarriers for dual delivery of alendronate (ALD), a bone-targeting bisphosphonate, and osteogenic growth peptide (OGP10-14), a peptide promoting bone formation. MSNs were synthesized and functionalized with amine groups via (3-aminopropyt)triethoxysilane (APTES) to enable both physical adsorption and chemical conjugation of therapeutic agents. Comprehensive physicochemical characterization employed transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and Brunauer-Emmett-Teller (BET) analysis to assess structural properties and thermal stability. Validated analytical methods based on UV-Visible spectrophotometry and high-performance liquid chromatography (HPLC) were developed for accurate ALD quantification. OGP (10-14) was synthesized via solid-phase peptide synthesis and characterized by mass spectrometry and NMR. Dual-loaded nanoformulations were prepared using carbamate linker chemistry for chemical conjugation and physical adsorption.

Biological evaluation using MG-63 osteoblast cells demonstrated excellent biocompatibility and efficient cellular uptake via confocal microscopy. Cell proliferation assays showed enhanced osteoblast growth, while mineralization assays revealed that chemically conjugated OGP (10-14)@ALD-MSN formulations significantly increased calcium deposition and mineral nodule formation compared to physically loaded systems.

The results demonstrate that MSN-based dual-delivery systems effectively combine sustained-release kinetics with enhanced osteogenic activity. These nanocarriers show considerable promise for treating bone disorders through localized, targeted delivery. Future work should focus on sterilization, scale-up manufacturing, long-term stability studies, and in vivo efficacy evaluation prior to clinical translation.

Thesis is embargoed until 31 July 2029.

Date of Award	Jul 2026
Original language	English
Awarding Institution	Queen's University Belfast
Supervisor	Thakur Raghu Raj Singh (Supervisor), Lalitkumar Vora (Supervisor) & Justin Tian (Supervisor)