Claw Shaped Polymeric Micelles-New Opportunities for the Pharmaceutical Sector
Lead Research Organisation:
University College London
Department Name: Pharmaceutics
Abstract
A number of molecular interactions have been harnessed by the pharmaceutical sector enable valuable drug compounds to be delivered to patients. Some molecular interactions involving water insoluble drugs are aimed at drug solubilisation, thus allowing the drugs to be administered. Despite all these efforts up to 40% of new chemical entities with proven biological activity still fail in development simply because a) they are insoluble in water and b) suitable and biocompatible drug solubilisers are unavailable. Available materials include low molecular weight surfactant solubilisers which have poor biocompatibility as they tend to lyse cells due precisely to their detergent nature and the resulting solutions are unstable to dilution. Block copolymer on the other hand are poor drug solubilisers. The proposal builds on work which has established that biocompatible (do not cause cell lysis) polymeric comb shapedsurfactants, in which soluble polymers bearing water insoluble pendant groups, are abto solubilise water insoluble molecules in aqueous media by specific intermolecularA number of molecular interactions have been harnessed by the pharmaceutical sector to enable valuable drug compounds to be delivered to patients. Some molecular interactions involving water insoluble drugs are aimed at drug solubilisation, thus allowing the drugs to be administered. Despite all these efforts up to 40% of new chemical entities with proven biological activity still fail in development simply because a) they are insoluble in water and b) suitable and biocompatible drug solubilisers are unavailable. Available materials include low molecular weight surfactant solubilisers which have poor biocompatibility as they tend to lyse cells due precisely to their detergent nature and the resulting solutions are unstable to dilution. Block copolymers on the other hand are poor drug solubilisers. The proposal builds on work which has established that biocompatible (do not cause cell lysis) polymeric comb shapedsurfactants, in which soluble polymers bearing water insoluble pendant groups, are able to solubilise water insoluble molecules in aqueous media by specific intermolecular events. Specifically the proposal examines a new polymer architecture - claw shaped polymeric surfactants (as shown in the Figure) in which the water insoluble molecule isheld in a hydrophobic pocket formed by each claw shaped surfactant molecule. The hydrophobic pocket will arise from the aggregation of the separate amphiphilic digits of the claw. At the University of Strathclyde, we have already worked out the tricky part of the synthesis and aim to synthesise a variety of polymeric amphiphiles, identify optimal architectures, using a newly developed high throughput system, and study the claw shaped polymeric surfactant self assembly as well as the molecular interactions between the new polymers and model drug molecules. Suitable candidates will undergo preliminary biological testing in order to establish proof of the delivery concept. Total cost = 213,174. The work fulfils the EPSRC Life Sciences Interface Programme objectives and contributes to the Council's mission to support innovative materials and engineering research.
Organisations
People |
ORCID iD |
Ijeoma Uchegbu (Principal Investigator) |
Publications
Al-Kulabi A
(2021)
Nanoparticulate Mycophenolic Acid Eye Drops - Analytical Validation of a High Performance Liquid Chromatography Assay and Stability Studies.
in Pharmaceutical nanotechnology
Badr MY
(2021)
A polymeric aqueous tacrolimus formulation for topical ocular delivery.
in International journal of pharmaceutics
Bonaccorso A
(2017)
Nose to brain delivery in rats: Effect of surface charge of rhodamine B labeled nanocarriers on brain subregion localization.
in Colloids and surfaces. B, Biointerfaces
Chooi KW
(2014)
Physical characterisation and long-term stability studies on quaternary ammonium palmitoyl glycol chitosan (GCPQ)--a new drug delivery polymer.
in Journal of pharmaceutical sciences
Fisusi F
(2015)
Abstract 5530: Chitosan amphiphile nanoparticles reduced the myelosuppressive effects of lomustine
in Cancer Research
Fisusi F
(2013)
Abstract 4519: Lomustine nanoparticles are effective brain cancer treatments.
in Cancer Research
Fisusi FA
(2018)
Nanomedicines in the treatment of brain tumors.
in Nanomedicine (London, England)
Gewin Virginia
(2018)
It takes more than a vow
in NATURE
Godfrey L
(2018)
Nanoparticulate peptide delivery exclusively to the brain produces tolerance free analgesia.
in Journal of controlled release : official journal of the Controlled Release Society
He S
(2021)
Down-regulation of GP130 signaling sensitizes bladder cancer to cisplatin by impairing Ku70 DNA repair signaling and promoting apoptosis.
in Cellular signalling