uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Carbon Dioxide-Mediated Generation of Hybrid Nanoparticles for Improved Bioavailability of Protein Kinase Inhibitors
Show others and affiliations
2014 (English)In: Pharmaceutical research, ISSN 0724-8741, E-ISSN 1573-904X, Vol. 31, no 3, 694-705 p.Article in journal (Refereed) Published
Abstract [en]

A versatile methodology is demonstrated for improving dissolution kinetics, gastrointestinal (GI) absorption, and bioavailability of protein kinase inhibitors (PKIs). The approach is based on nanoparticle precipitation by sub- or supercritical CO2 together with a matrix-forming polymer, incorporating surfactants either during or after nanoparticle formation. Notably, striking synergistic effects between hybrid PKI/polymer nanoparticles and surfactant added after particle formation is investigated. The hybrid nanoparticles, consisting of amorphous PKI embedded in a polymer matrix (also after 12 months), display dramatically increased release rate of nilotinib in both simulated gastric fluid and simulated intestinal fluid, particularly when surfactants are present on the hybrid nanoparticle surface. Similar results indicated flexibility of the approach regarding polymer identity, drug load, and choice of surfactant. The translation of the increased dissolution rate found in vitro into improved GI absorption and bioavalilability in vivo was demonstrated for male beagle dogs, where a 730% increase in the AUC(0-24h) was observed compared to the benchmark formulation. Finally, the generality of the formulation approach taken was demonstrated for a range of PKIs. Hybrid nanoparticles combined with surfactant represent a promising approach for improving PKI dissolution rate, providing increased GI absorption and bioavailability following oral administration.

Place, publisher, year, edition, pages
2014. Vol. 31, no 3, 694-705 p.
Keyword [en]
bioavailability, carbon dioxide, hybrid, nanoparticle, protein kinase inhibitor
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-222403DOI: 10.1007/s11095-013-1191-4ISI: 000332008800013OAI: oai:DiVA.org:uu-222403DiVA: diva2:711607
Available from: 2014-04-10 Created: 2014-04-10 Last updated: 2014-04-10Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Lennernäs, HansMalmsten, Martin
By organisation
Department of Pharmacy
In the same journal
Pharmaceutical research
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 185 hits
ReferencesLink to record
Permanent link

Direct link