Investigation of optimum production conditions and the stability of ?-cyclodextrin-perfluorocarbon nanocone clusters for histotripsy applications

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dc.authorid0000-0003-2776-5807
dc.contributor.authorMustafa, Waleed
dc.contributor.authorHall, Sarah
dc.contributor.authorHuynh, Laura
dc.contributor.authorMannasse, Rachel
dc.contributor.authorLüleburgaz, Serter
dc.contributor.authorVlaisavljevich, Eli
dc.contributor.authorYüksel Durmaz, Yasemin
dc.date.accessioned2024-05-30T11:31:16Z
dc.date.available2024-05-30T11:31:16Z
dc.date.issued2024
dc.departmentİstanbul Medipol Üniversitesi, Mühendislik ve Doğa Bilimleri Fakültesi, Biyomedikal Mühendisliği Bölümü
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Sağlık Bilim ve Teknolojileri Araştırma Enstitüsü
dc.description.abstractNanocone clusters (NCCs) have been developed as clusters with inclusion complexes of FDA-approved ?-cyclodextrin (?CD) and perfluorocarbons (PFC) (i.e., perfluoropentane (PFP) and perfluorohexane (PFH)) and have shown promise in nanoparticle-mediated histotripsy (NMH) applications owing to their lowered cavitation threshold, ease of production, and fluorocarbon quantification. However, there is still a lack of information on the best conditions of the synthesis of NCCs as a product that can have a maximum determinable fluorocarbon content and maintain the stability of the NCC during synthesis and when used as histotripsy agents or exposed to physiological conditions. These concerns about the stability of the clusters and the best possible formulation are investigated in the current work. The cluster formation potential was tested taking into consideration the nature of both PFCs and ?CD by employing different synthesis conditions in terms of solution and environmental parameters such as concentration of solvent, stoichiometry between ?CD and PFCs, temperature, pH, solvent type, etc. The best route of synthesis was then translated into various batch sizes and investigated in terms of the PFC loading and yield. These studies revealed that preparing NCCs in double-distilled water in an ice bath at the optimized solution concentration gave the highest yields and optimal PFC loading, as determined from gas chromatography. Furthermore, the stability of the clusters with different stoichiometries was scrutinized in varying concentrations, mechanical disruption times, pH levels, and temperature conditions, showing effects on each cluster’s particle size in dynamic light scattering, visualized in transmission electron microscopy, and cavitation behavior in agarose gel tissue phantoms. These studies revealed stable clusters for all formulations, with PFH-containing NCCs emerging to be the most stable in terms of their cluster size and bubble formation potential in histotripsy. Finally, the shelf life of these clusters was investigated using DLS, which revealed a stable cluster. In conclusion, NCCs have shown high stability in terms of both synthesis, which can be replicated in gram-level production, and the cluster itself, which can be exposed to harsher conditions and still form stable bubbles in histotripsy.
dc.identifier.citationMustafa, W., Hall, S., Huynh, L., Mannasse, R., Lüleburgaz, S., Vlaisavljevich, E. ... Yüksel Durmaz, Y. (2024). Investigation of optimum production conditions and the stability of ?-cyclodextrin-perfluorocarbon nanocone clusters for histotripsy applications. Molecular Pharmaceutics, 21(5), 2383-2393. http://dx.doi.org/10.1021/acs.molpharmaceut.3c01178
dc.identifier.doi10.1021/acs.molpharmaceut.3c01178
dc.identifier.endpage2393
dc.identifier.issn1543-8384
dc.identifier.issn1543-8392
dc.identifier.issue5
dc.identifier.pmid38551360
dc.identifier.scopus2-s2.0-85189567164
dc.identifier.scopusqualityQ1
dc.identifier.startpage2383
dc.identifier.urihttp://dx.doi.org/10.1021/acs.molpharmaceut.3c01178
dc.identifier.urihttps://hdl.handle.net/20.500.12511/12543
dc.identifier.volume21
dc.identifier.wos001194424500001en_US
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorMustafa, Waleed
dc.institutionauthorYüksel Durmaz, Yasemin
dc.language.isoen
dc.relation.ecinfo:eu-repo/grantAgreement/NIBIB/118Z324
dc.relation.ispartofMolecular Pharmaceuticsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.relation.tubitakinfo:eu-repo/grantAgreement/TUBITAK/R21EB027979
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectCyclodextrin
dc.subjectHistotripsy
dc.subjectNanocone Clusters
dc.subjectNanoparticle-Mediated Histotripsy
dc.subjectPerfluorocarbon
dc.titleInvestigation of optimum production conditions and the stability of ?-cyclodextrin-perfluorocarbon nanocone clusters for histotripsy applications
dc.typeArticle

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