Thiomers and thiomer-based nanoparticles in protein and DNA drug delivery.
BACKGROUND
Thanks to advances in biotechnology, more and more highly efficient protein- and DNA-based drugs have been developed. Unfortunately, these kinds of drugs underlie poor non-parental bioavailability. To overcome hindrances like low mucosal permeability and enzymatic degradation polymeric excipients are utilized as drug carrier whereat thiolated excipients showed several promising qualities in comparison to the analogical unmodified polymer.


METHODS
The article deals with the comparatively easy modification of well-established polymers like chitosan or poly(acrylates) to synthesize thiomers. Further, the recently developed "next generation" thiomers e.g. preactivated or S-protected thiomers are introduced. Designative properties like mucoadhesion, uptake and permeation enhancement, efflux pump inhibition and protection against enzymatic degradation will be discussed and differences between first and next generation thiomers will be pointed out. Additionally, nanoparticles prepared with thiomers will be dealt with regarding to protein and DNA drug delivery as thiomers seem to be a promising approach to avoid parenteral application.


CONCLUSIONS
Properties of thiomers per se and results of in vivo studies carried out so far for peptide and DNA drugs demonstrate their potential as multifunctional excipients. However, further investigations and optimizations have to be done before establishing a carrier system ready for clinical approval.
University of Innsbruck, Institute of Pharmacy, Department of Pharmaceutical Technology, Innrain 80/82, 6020 Innsbruck, Austria.
Sabine
S
Hauptstein
Andreas
A
Bernkop-Schnürch
D000180:Acrylic Resins / Q000737:chemistry; D000818:Animals; D001692:Biological Transport; D048271:Chitosan / Q000737:chemistry; D004247:DNA / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000008:administration & dosage*; D011108:Polymers / Q000737:chemistry*
D000180:Acrylic Resins; D004337:Drug Carriers; D010455:Peptides; D011108:Polymers; C006903:carbopol 940; D004247:DNA; D048271:Chitosan