Biomedical Engineering Reference
In-Depth Information
5.
Nanoparticle technologies
The first described nanoscale drug delivery systems were lipid vesicles [94].
The first application of targeted liposomes was reported in 1980 [95]. Since
then, research has led to important progress in the development of nano-
particles engineered to have multifunctional capabilities, as well as “smart”
properties such as the ability to respond to the environment, to facilitate
more effective drug delivery strategies. Nanoparticle technologies for nano-
medicine include polymeric NPs, polymer-drug conjugates NPs, micelles,
liposomes, metal complexes, carbon derivates, peptides NPs, silica NPs,
quantum dots and dendrimers. The diversity of delivery systems allows
nanoparticles to be developed with a diverse array of shapes, size, and com-
ponents which enables them to be tailored for specific applications. However,
the primary consideration when designing any drug delivery system is to
achieve more effective therapies, by controlling the drug concentration in
the therapeutic window, reducing cytotoxic effects, and improving patient
compliance.
5.1 Polymeric and polymer-drug conjugate nanoparticles
Polymeric NPs are synthesized using various methods according to the
needs of the application and type of drugs to be encapsulated. These NPs are
extensively used for the nanoencapsulation of various useful bioactive mol-
ecules and medicinal drugs. Polymeric NPs are structured in two different
forms, nanospheres and nanocapsules. They are, respectively, characterized
by a matrix system in which the drug is dispersed, and a reservoir in which
the drug is confined in a hydrophobic core surrounded by a single polymeric
membrane (core-shell structure). These carriers show a higher stability in bi-
ological fluids and against the enzymatic metabolism. Their nanometer-size
promotes effective permeation through cell membranes and stability in the
blood stream. Polymers are being developed to create delivery systems with
excellent drug and protein loading and release properties, a long shelf life,
and little toxicity. The core matrix of these NPs can be composed of various
biodegradable polymers, such as poly(lactic-coglycolic acid) (PLGA), chito-
san, poly(alkylcyanoacrylate) (PACA), poly(butylcyanoacrylate) (PBCA),
poly(lysine), poly(e-caprolactone) (PCL), and PAsp (polyaspartate). The
degradation drug release rate of these polymers can be controlled by ad-
justing their molecular mass, and in the case of copolymers, their composi-
tion and microstructure [96]. Polymer NPs have been used as transport
vectors for various peptide CNS delivery after intravenous injection, such
as hexapeptide dalargin, loperamide, tubocurarine and doxorubicin. PLGA
(poly-d,l-lactide-co-glycolide) is one of the most successfully used biode-
gradable nanosystems because it undergoes hydrolysis in the body to pro-
duce the biodegradable metabolite monomers, lactic acid and glycolic acid.
Surface modification of PLGA, drug encapsulation methods and particle
