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Sustained drug release in nanomedicine: a long-acting nanocarrier-based formulation for glaucoma.
- Source :
-
ACS nano [ACS Nano] 2014 Jan 28; Vol. 8 (1), pp. 419-29. Date of Electronic Publication: 2014 Jan 06. - Publication Year :
- 2014
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Abstract
- Therapeutic nanomedicine has concentrated mostly on anticancer therapy by making use of the nanosize for targeted therapy. Such nanocarriers are not expected to have sustained release of the bioactive molecule beyond a few days. There are other conditions where patients can benefit from sustained duration of action following a single instillation, but achieving this has been difficult in nanosized carriers. An important prerequisite for sustained delivery over several months is to have sufficiently high drug loading, without disruption or changes to the shape of the nanocarriers. Here we report on successful development of a drug-encapsulated nanocarrier for reducing intraocular pressure in a diseased nonhuman primate model and explain why it has been possible to achieve sustained action in vivo. The drug is a prostaglandin derivative, latanoprost, while the carrier is a nanosized unilamellar vesicle. The mechanistic details of this unique drug-nanocarrier combination were elucidated by isothermal titration calorimetry. We show, using Cryo-TEM and dynamic light scattering, that the spherical shape of the liposomes is conserved even at the highest loading of latanoprost and that specific molecular interactions between the drug and the lipid are the reasons behind improved stability and sustained release. The in vivo results clearly attest to sustained efficacy of lowering the intraocular pressure for 120 days, making this an excellent candidate to be the first truly sustained-release nanomedicine product. The mechanistic details we have uncovered should enable development of similar systems for other conditions where sustained release from nanocarriers is desired.
Details
- Language :
- English
- ISSN :
- 1936-086X
- Volume :
- 8
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- ACS nano
- Publication Type :
- Academic Journal
- Accession number :
- 24392729
- Full Text :
- https://doi.org/10.1021/nn4046024