Biomedical Engineering Reference
In-Depth Information
16.1.6
o
ther
N
aNopartIcles
16.1.6.1 Poly(Alkyl-Cyanoacrylate)
Poly (acyl-cyanocrylate) (PACA) is a colloidal suspension of nanoparticles shown to prolong the cor-
neal penetration of hydrophilic and lipophilic drugs in the eye [18]. These compounds have a strong
shelf life, as they maintained their mean size and appeared unchanged when stored at room tem-
perature for 6 months [18]. The corneal penetration may be due to their colloidal nature; however, its
therapeutic application may be hindered by the disruption caused to the corneal cell membrane [18].
16.1.6.2 Poly-
ε
-Caprolactone Nanoparticles and Nanocapsules
Poly-ε-caprolactone (PECL) is a hydrophobic, biodegradable, and biocompatible polymer of
ε-caprolactone [3]. PECL nanoparticles are slowly broken down in biological systems by the hydro-
lysis of ester linkages but the nanoparticles can be mixed with more hydrophilic polymers to form
copolymers that can be broken down at faster rates [3,19]. Experimental studies in rabbit eyes
showed that the nanoparticles are well tolerated without any signs of inflammation in the anterior
and posterior segments of the eye [20].
PECL nanocapsules enhance the penetration of lipophilic drugs in ocular tissues without dam-
aging the cell membranes, with penetration rates more favorable than PECL nanoparticles [18].
The sizes of nanocapsules did not change after 6 months at room temperature, suggesting that the
polymer coating imparts stability to the nanocapsules [18].
16.1.6.3 Nanomicelles
Nanomicelles, up to 100 nm in size, are a low-toxicity colloidal dispersion of molecules with a
hydrophobic core and hydrophilic shell [1,21]. These molecules provide an excellent method by
which to solubilize hydrophobic drugs with therapeutic concentrations and administer them to
hydrophilic tissues, thereby lowering drug degradation and enhancing permeability [1]. Since the
hydrophilic sclera is an efficient therapeutic pathway to the posterior eye, nanomicelles make it
easier for hydrophobic drugs to efficiently diffuse to the posterior eye with minimal degradation
[1]. In addition, the hydrophilicity of the nanomicelle shell may confer resistance against systemic
circulation washout
via
ocular blood and lymphatic vessels [1]. This relatively new nanotherapeutic
molecule has shown little toxicity in biological systems, but more toxicological studies are war-
ranted before its widespread use [1].
16.1.6.4 Poly[(Cholesteryl Oxocarbonylamido Ethyl) Methyl Bis(Ethylene)
Ammonium Iodide]
Poly[(cholesteryl oxocarbonylamido ethyl) methyl bis(ethylene) ammonium iodide] (PCEP) is a
DNA-condensing agent with gene therapy potential in the eye [5]. Similar to MNP, PCEP did not
induce inflammation when injected intravitreally or subretinally [5]. These relatively harmless mol-
ecules did not attract white blood cells to the site of injection [5]. Because of its inert biodegradabil-
ity, and low toxicity, it serves as a potential ocular nanoparticle transfection agent [5].
16.1.6.5 Acrylate Polymers (Eudragit
®
)
Eudragit is a nanoparticle that improves drug stability and maximizes drug dosages and effects [2].
The biological activity of Eudragit can be directly manipulated by the choice of polymer used to
make the Eudragit copolymer [2]. There were no reports of ocular toxicity after 10 min of applica-
tion, with mild irritation in the first 10 min reported by 20-30% of subjects [2]. Because of its low-
to nontoxicity, Eudragit serves as an ocular topically therapeutic nanoparticle.
16.1.6.6 Solid Lipid Nanoparticles
Solid lipid nanoparticles (SLNs), ranging in size up to 400 nm, are biodegradable and biocompat-
ible, and have been used as nanoparticles since the 1990s [2]. The advantage of these nanoparticles
