Thesis

Silk nanoparticles for drug delivery applications

Creator
Rights statement
Awarding institution
  • University of Strathclyde
Date of award
  • 2014
Thesis identifier
  • T13895
Qualification Level
Qualification Name
Department, School or Faculty
Abstract
  • Silk from Bombyx mori is being used in humans for loading applications due to its excellent mechanical properties and biocompatibility. Furthermore silk is emerging as potential biomaterial for biomedical applications such as drug delivery and tissue-engineering. The aim of this thesis was to examine the potential of silk nanoparticles for drug delivery by characterizing (1) particle size, (2) zeta potential, (3) stability, (4) loading efficiency and (5) in vitro drug release. First, silk nanoparticles were generated by a desolvation method using acetone. The resulting particle size and zeta potential were measured using dynamic light scattering, which revealed nano-sized particles (104.20 ± 1.70 nm) with narrow polydispersity index (0.11 ± 0.01), and negative surface charge (-56.38 ± 5.60 mV). In water silk nanoparticles were stable over 4 weeks over wide temperature range (4°C to 37°C). Second, nanoparticles were surface modified with polyethylene glycol (PEG) by reacting cyanuric chloride activated methoxypolyethylene glycol (5000 g/mol) with silk. The amount of activated PEG grafted to particle's surface was controlled by the weight ratio to silk nanoparticles, resulting in 19.39 ± 1.93% w/w conjugated PEG. The stability of PEGylated silk nanoparticles in water and in phosphate buffered saline at pH 7.4 was studied and compared with unmodified silk nanoparticles; PEGylated silk nanoparticles had a superior stability over the unmodified nanoparticles in phosphate buffered saline. Third, the drug loading and release behavior of silk nanoparticles and PEGylated silk nanoparticles was investigated with two model drugs; propranolol HCl and doxorubicin HCl. The native and PEGylated silk nanoparticles showed high encapsulation efficiency for doxorubicin HCl (100% w/w) and propranolol HCl (> 93% w/w). The release of doxorubicin HCl over 14 days was pH dependent, and showed highest release at pH 4.5 from native and PEGylated silk nanoparticles as compared to pH 6.0 and 7.4 (pH 4.5>>6.0>7.4). PEGylation significantly impacted on the release behavior of doxorubicin HCl from silk nanoparticles by showing faster release at pH 4.5 and 6.0 in comparison to unmodified silk nanoparticles. In conclusion, silk nanoparticles and PEGylated silk nanoparticles showed promise as potential anticancer drug delivery systems and warrant future in vitro studies.
Resource Type
DOI
Date Created
  • 2014
Former identifier
  • 1041831

Relations

Items