Academic Journal
Impact of the physical-chemical properties of poly(lactic acid)-poly (ethylene glycol) polymeric nanoparticles on biodistribution
| العنوان: | Impact of the physical-chemical properties of poly(lactic acid)-poly (ethylene glycol) polymeric nanoparticles on biodistribution |
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| المؤلفون: | Jackman, MJ, Li, WM, Smith, A, Workman, D, Treacher, KE, Corrigan, A, Abdulrazzaq, F, Sonzini, S, Nazir, Z, Lawrence, M. Jayne, Mahmoudi, N, Cant, D, Counsell, J, Cairns, J, Ferguson, D, Lenz, E, Baquain, S, Madla, CM, van Pelt, S, Moss, J, Peter, A, Puri, Sanyogitta, Ashford, M, Mazza, M |
| المصدر: | Jackman , MJ , Li , WM , Smith , A , Workman , D , Treacher , KE , Corrigan , A , Abdulrazzaq , F , Sonzini , S , Nazir , Z , Lawrence , M J , Mahmoudi , N , Cant , D , Counsell , J , Cairns , J , Ferguson , D , Lenz , E , Baquain , S , Madla , CM , van Pelt , S , Moss , J , Peter , A , Puri , S , Ashford , M & Mazza , M 2024 , .... |
| سنة النشر: | 2024 |
| المجموعة: | The University of Manchester: Research Explorer - Publications |
| مصطلحات موضوعية: | Bioanalytical assay, Biodistribution, Characterization, Critical quality attributes, Cryo-TEM, HAXPES, In vitro release, Nanoparticles, PLA-PEG, SANS |
| الوصف: | Nanoparticle (NP) formulations are inherently polydisperse making their structural characterization and justification of specifications complex. It is essential, however, to gain an understanding of the physico-chemical properties that drive performance in vivo. To elucidate these properties, drug-containing poly(lactic acid) (PLA)–poly(ethylene glycol) (PEG) block polymeric NP formulations (or PNPs) were sub-divided into discrete size fractions and analyzed using a combination of advanced techniques, namely cryogenic transmission electron microscopy, small-angle neutron and X-ray scattering, nuclear magnetic resonance, and hard-energy X-ray photoelectron spectroscopy. Together, these techniques revealed a uniquely detailed picture of PNP size, surface structure, internal molecular architecture and the preferred site(s) of incorporation of the hydrophobic drug, AZD5991, properties which cannot be accessed via conventional characterization methodologies. Within the PNP size distribution, it was shown that the smallest PNPs contained significantly less drug than their larger sized counterparts, reducing overall drug loading, while PNP molecular architecture was critical in understanding the nature of in vitro drug release. The effect of PNP size and structure on drug biodistribution was determined by administrating selected PNP size fractions to mice, with the smaller sized NP fractions increasing the total drug-plasma concentration area under the curve and reducing drug concentrations in liver and spleen, due to greater avoidance of the reticuloendothelial system. In contrast, administration of unfractionated PNPs, containing a large population of NPs with extremely low drug load, did not significantly impact the drug's pharmacokinetic behavior - a significant result for nanomedicine development where a uniform formulation is usually an important driver. We also demonstrate how, in this study, it is not practicable to validate the bioanalytical methodology for drug released in vivo due to the NP formulation ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | https://research.manchester.ac.uk/en/publications/1cb31e5f-b3af-461e-b549-b42b13214619 |
| DOI: | 10.1016/j.jconrel.2023.11.043 |
| الاتاحة: | https://research.manchester.ac.uk/en/publications/1cb31e5f-b3af-461e-b549-b42b13214619 https://doi.org/10.1016/j.jconrel.2023.11.043 https://pure.manchester.ac.uk/ws/files/304348406/COREL-D-23-01687_R1.pdf https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_starter&SrcAuth=WosAPI&KeyUT=WOS:001133579900001&DestLinkType=FullRecord&DestApp=WOS http://www.scopus.com/inward/record.url?scp=85178640950&partnerID=8YFLogxK https://www.mendeley.com/catalogue/ca936c82-1ec4-3241-af0e-454f5591c3a6/ |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.7263955 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.jconrel.2023.11.043 |
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