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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 03757naa a2200457 4500 | |
| 001 | oai:DiVA.org:liu-200260 | |
| 003 | SwePub | |
| 008 | 240119s2023 | |||||||||||000 ||eng| | |
| 024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-2002602 URI |
| 024 | 7 | a https://doi.org/10.1021/acs.molpharmaceut.3c006632 DOI |
| 040 | a (SwePub)liu | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Mcgowan, Asmaau DelSiTech Ltd, Finland4 aut |
| 245 | 1 0 | a Injectable Biodegradable Silica Depot for Controlled Subcutaneous Delivery of Antisense Oligonucleotides with beyond Monthly Administration |
| 264 | 1 | b AMER CHEMICAL SOC,c 2023 |
| 338 | a print2 rdacarrier | |
| 520 | a Single-stranded antisense oligonucleotides (ASOs) are typically administered subcutaneously once per week or monthly. Less frequent dosing would have strong potential to improve patient convenience and increase adherence and thereby for some diseases result in more optimal therapeutic outcomes. Several technologies are available to provide sustained drug release via subcutaneous (SC) administration. ASOs have a high aqueous solubility and require relatively high doses, which limits the options available substantially. In the present work, we show that an innovative biodegradable, nonporous silica-based matrix provides zero-order release in vivo (rats) for at least 4 weeks for compositions with ASO loads of up to about 100 mg/mL (0.5 mL injection) without any sign of initial burst. This implies that administration beyond once monthly can be feasible. For higher drug loads, substantial burst release was observed during the first week. The concentrations of unconjugated ASO levels in the liver were found to be comparable to corresponding bolus doses. Additionally, infusion using a minipump shows a higher liver exposure than SC bolus administration at the same dose level and, in addition, clear mRNA knockdown and circulating protein reduction comparable to SC bolus dosing, hence suggesting productive liver uptake for a slow-release administration. | |
| 650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Farmaceutiska vetenskaper0 (SwePub)301012 hsv//swe |
| 650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Pharmaceutical Sciences0 (SwePub)301012 hsv//eng |
| 653 | a oligonucleotide; long-acting injectable; silica-basedformulation; pharmacokinetics; subcutaneous | |
| 700 | 1 | a Gennemark, Peteru Linköpings universitet,Avdelningen för medicinsk teknik,Tekniska fakulteten,AstraZeneca, Sweden4 aut0 (Swepub:liu)petge96 |
| 700 | 1 | a Akieh-Pirkanniemi, Marcelineu DelSiTech Ltd, Finland4 aut |
| 700 | 1 | a Wirman, Lindau DelSiTech Ltd, Finland4 aut |
| 700 | 1 | a Davies, Nigelu AstraZeneca, Sweden4 aut |
| 700 | 1 | a Elebring, Marieu AstraZeneca, Sweden4 aut |
| 700 | 1 | a Tivesten, Annau AstraZeneca, Sweden4 aut |
| 700 | 1 | a Strimfors, Marieu AstraZeneca, Sweden4 aut |
| 700 | 1 | a Holtta, Mikkou AstraZeneca, Sweden4 aut |
| 700 | 1 | a Soderberg, Magnusu AstraZeneca, Sweden4 aut |
| 700 | 1 | a Berntsson, Veronicau AstraZeneca, Sweden4 aut |
| 700 | 1 | a Balas, Danielau AstraZeneca, Sweden4 aut |
| 700 | 1 | a Koskinen, Mikau DelSiTech Ltd, Finland4 aut |
| 700 | 1 | a Leino, Lasseu DelSiTech Ltd, Finland4 aut |
| 700 | 1 | a Abrahmsen-Alami, Susannau AstraZeneca, Sweden4 aut |
| 710 | 2 | a DelSiTech Ltd, Finlandb Avdelningen för medicinsk teknik4 org |
| 773 | 0 | t Molecular Pharmaceuticsd : AMER CHEMICAL SOCg 21:1, s. 143-151q 21:1<143-151x 1543-8384x 1543-8392 |
| 856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-200260 |
| 856 | 4 8 | u https://doi.org/10.1021/acs.molpharmaceut.3c00663 |
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