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- Ansari, Shaquib Rahman, 1993-
(författare)
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From design to application: Iron oxide nanoparticles for imaging and therapeutics in inflammatory and infectious diseases
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Superparamagnetic iron oxide nanoparticles (SPIONs) are a promising advancement in nanomedicine, demonstrating remarkable potential in both diagnostic and therapeutic applications. They can be magnetized in a magnetic field and do not show permanent magnetization, allowing precise localization within the body. Under an alternating magnetic field, SPIONs generate heat, which can be used for magnetic hyperthermia therapy against cancer or to trigger drug release. Diagnostically, they are widely used as contrast agents for magnetic resonance imaging (MRI), while magnetic particle imaging (MPI) is an emerging preclinical diagnostic technique using SPIONs as tracers.Despite these promising applications, the clinical utility of SPIONs is hindered by challenges related to scalable and reproducible manufacturing. Focused efforts are also needed to improve MPI resolution. Moreover, the application of magnetic hyperthermia for treating inflammatory and infectious conditions remains relatively underexplored. Therefore, the primary objective of this thesis was to develop SPIONs tailored for imaging and therapy of inflammatory and infectious diseases through scalable manufacturing techniques. The first part of the study involved a systematic review to examine the most pertinent research on use of SPIONs for diagnosing and treating chronic inflammatory diseases. MRI was identified as the predominant application of SPIONs. However, there was limited exploration of MPI and magnetic hyperthermia for imaging and treating inflammatory diseases, respectively.In the second project, a risk-based pharmaceutical quality by design approach was used to optimize SPIONs for magnetic hyperthermia. The effect of nanoparticle properties on MPI performance was systematically investigated in the third project. Additionally, these projects established flame spray pyrolysis as a scalable and reproducible technique, for synthesizing nanoparticles with complex stoichiometry for magnetic hyperthermia and MPI.In final part of the study, SPIONs were incorporated into composites by scalable techniques, to improve the treatment of inflammatory and infectious diseases. SPIONs were incorporated in tablets with an anti-inflammatory drug, celecoxib. The drug solubility improved significantly through magnetic hyperthermia-induced in situ amorphization. SPIONs were also incorporated into microfibers, and heat dissipation from magnetic microfibers was used with doxycycline against methicillin-resistant Staphylococcus aureus. This resulted in substantial reduction in bacterial growth compared to using the drug alone.This thesis introduced systematic exploration of SPION properties and their functional performance, established a scalable synthesis technique for their production, and developed novel systems for wider adaptation of SPIONs in biomedical applications.
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| 2. |
- Ansari, Shaquib Rahman, 1993-, et al.
(författare)
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Hyperthermia-Induced In Situ Drug Amorphization by Superparamagnetic Nanoparticles in Oral Dosage Forms
- 2022
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 14:19, s. 21978-21988
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Tidskriftsartikel (refereegranskat)abstract
- Superparamagnetic iron oxide nanoparticles (SPIONs) generate heat upon exposure to an alternating magnetic field (AMF), which has been studied for hyperthermia treatment and triggered drug release. This study introduces a novel application of magnetic hyperthermia to induce amorphization of a poorly aqueous soluble drug, celecoxib, in situ in tablets for oral administration. Poor aqueous solubility of many drug candidates is a major hurdle in oral drug development. A novel approach to overcome this challenge is in situ amorphization of crystalline drugs. This method facilitates amorphization by molecular dispersion of the drug in a polymeric network inside a tablet, circumventing the physical instability encountered during the manufacturing and storage of conventional amorphous solid dispersions. However, the current shortcomings of this approach include low drug loading, toxicity of excipients, and drug degradation. Here, doped SPIONs produced by flame spray pyrolysis are compacted with polyvinylpyrrolidone and celecoxib and exposed to an AMF in solid state. A design of experiments approach was used to investigate the effects of SPION composition (Zn0.5Fe2.5O4 and Mn0.5Fe2.5O4), doped SPION content (10–20 wt %), drug load (30–50 wt %), and duration of AMF (3–15 min) on the degree of drug amorphization. The degree of amorphization is strongly linked to the maximum tablet temperature achieved during the AMF exposure (r = 0.96), which depends on the SPION composition and content in the tablets. Complete amorphization is achieved with 20 wt % Mn0.5Fe2.5O4 and 30 wt % celecoxib in the tablets that reached the maximum temperature of 165.2 °C after 15 min of AMF exposure. Furthermore, manganese ferrite exhibits no toxicity in human intestinal Caco-2 cell lines. The resulting maximum solubility of in situ amorphized celecoxib is 5 times higher than that of crystalline celecoxib in biorelevant intestinal fluid. This demonstrates the promising capability of SPIONs as enabling excipients to magnetically induce amorphization in situ in oral dosage forms.
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