First name
Smbat
Last name
Gevorgyan
Year of Study
Thesis Title
Novel Poly(amidoamine) Nanoparticles Designed for Drug Delivery to the Central Nervous System
Thesis Abstract
With the aging population, central nervous system diseases are becoming increasingly widespread.
However, the treatment of such diseases represents a challenge mainly due to the presence of the
blood-brain barrier, which effectively blocks most of drugs to pass into the central nervous system
and impedes the treatment of diseases. Therefore, effective ways of drug transport to the central
nervous system are highly required.
Polymeric nanoparticles are drug delivery vectors that have high specificity to their targeted sites and
increasingly enhance the stability of encapsulated drugs. Poly(amidoamines) are a promising family of
synthetic polymers that can be used in nanoparticles synthesis. Nanoparticles synthesized from linear
poly(amidoamines) show very good biocompatibility levels and specific targeting properties.
Nevertheless, those nanoparticles are mainly synthesized by self-assembly and usually lack long-term
stability.
In this study we developed innovative poly(amidoamine) nanoparticles synthesized by ultraviolet light
assisted photo-crosslinking. The synthesis method had an advantage of being simple, did not require
toxic organic solvents and was shown to be easily scaled-up. Moreover, poly(amidoamine)
nanoparticles were coated by Polysorbate 80 surfactant, which not only increased the nanoparticles
stability but also gave them central nervous system targeting properties. Poly(amidoamine)
nanoparticles were able to successfully encapsulate model therapeutic compounds and release them
in a slow and controlled manner. Furthermore, the nanoparticles showed high permeability levels
across an in vitro blood brain barrier model.
The developed poly(amidoamine) nanoparticles show great potential to be used as delivery vectors to
the central nervous system.
However, the treatment of such diseases represents a challenge mainly due to the presence of the
blood-brain barrier, which effectively blocks most of drugs to pass into the central nervous system
and impedes the treatment of diseases. Therefore, effective ways of drug transport to the central
nervous system are highly required.
Polymeric nanoparticles are drug delivery vectors that have high specificity to their targeted sites and
increasingly enhance the stability of encapsulated drugs. Poly(amidoamines) are a promising family of
synthetic polymers that can be used in nanoparticles synthesis. Nanoparticles synthesized from linear
poly(amidoamines) show very good biocompatibility levels and specific targeting properties.
Nevertheless, those nanoparticles are mainly synthesized by self-assembly and usually lack long-term
stability.
In this study we developed innovative poly(amidoamine) nanoparticles synthesized by ultraviolet light
assisted photo-crosslinking. The synthesis method had an advantage of being simple, did not require
toxic organic solvents and was shown to be easily scaled-up. Moreover, poly(amidoamine)
nanoparticles were coated by Polysorbate 80 surfactant, which not only increased the nanoparticles
stability but also gave them central nervous system targeting properties. Poly(amidoamine)
nanoparticles were able to successfully encapsulate model therapeutic compounds and release them
in a slow and controlled manner. Furthermore, the nanoparticles showed high permeability levels
across an in vitro blood brain barrier model.
The developed poly(amidoamine) nanoparticles show great potential to be used as delivery vectors to
the central nervous system.
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