Biomedical Engineering Reference
In-Depth Information
lipids, which are biodegradable with simple natural processes such as enzyme digestion [38]. The
biodegradability of SLNs is one of the most important advantages in making them an outstand-
ing drug delivery vehicle. These lipids and their degradation products are considered nontoxic to
human body cells. However, owing to their nanosize range, their biotoxicity is an important issue,
as the human body reacts very differently to nanoparticles as compared with larger particles of the
same material. It has been reported that lipid carriers prepared with several lipids and emulsifying
agents did not exhibit any cytotoxicity up to the concentration of 2.5% lipids [39]. Furthermore, it has
been shown that higher concentration of 10% lipids led to a viability of 80% human granulocytes in
culture [39]. Several examples of nanotoxicity of inorganic nanoparticles have recently been docu-
mented. In this chapter, we have drawn parallel to the toxicity reported for other nanoparticles that
can be associated with PNs and SLNs along with citing specific examples for PNs and SLNs.
7.3.2 p
oteNtIal
M
echaNIsM
of
N
aNotoxIcIty
Table 7.3 summarizes reported works on cytotoxicity of various nanoparticles and the mechanisms
of toxicity along with potentially useful design methods. As of today, most of the research on nano-
toxicity has been done on the eukaryotic cells [40]. The common mechanisms of action that can lead
to nanotoxicity include cell wall destruction, oxidative stress, protein denaturation, interaction of
ions with cellular materials, and so on [41]. The chemical reactivity and biological activity of nano-
sized particles are often greater than larger-sized particles and thus increase the potential of toxicity.
Nanoparticles are also much more mobile and have greater access to cellular material. Cationic and
ionic polymers are commonly used in the pharmaceutical industry and they have the potential to
significantly interact with the cellular material and cause toxicity. The above-mentioned mechanism
of toxicity can also be associated with SLNs if the particle size is less than 100 nm although no
specific studies have been done.
7.3.2.1 Size of Nanoparticles
Nanoparticles having sizes less than 100 nm have greater potential for toxicity as size can sig-
nificantly affect particle properties. Smaller-sized particles usually have greater solubility and the
adhesiveness to surfaces/membranes. Pharmaceutical advantages such as increasing solubility and
drug targeting to specific sites justify the use of these smaller-sized particles but there is a second
important size limit, the 100 nm. Larger particles can only enter the cell by phagocytosis and can
only be taken up by macrophages. Therefore, these particles possess a lower toxicity risk. Particles
below 100 nm can be internalized by any cell through endocytosis; thus, these particles may have
a higher toxicity risk. There are many examples of PNs with sizes less than 100 nm, for example,
Zou et al. [59] developed the curcumin PN using PLGA-PEG-PLGA triblock polymer, while Woo
et al. [60] used diblock copolymer, polyethylene glycol-poly-l-lactic acid (mPEG-PLA), monova-
lent metal salt of a biodegradable polyester (d,l-PLACOONa), and calcium chloride to prepare PNs
of size less than 100 nm. Furthermore, Fang et al. [61] developed an SLN of size less than 50 nm
for a novel chemotherapeutic agent (PK-L4), an analog of amsacrine. In another example, Jeon
et al. [62] prepared a surface-modified SLN containing retinyl palmitate by the hot-melt method
using Gelucire 50/13 and Precirol ATO5 with dicetyl phosphate as surface modifier. The particle
size of these SLNs was less than 50 nm. Table 7.4 showed the applications, concerns, and biologi-
cal/mechanistic studies of inhaled nanoparticles of particle size less than 100 nm and greater than
500 nm [63]. The study focuses on inhaled nanoparticles and is important to mention as several PNs
and SLNs are designed to deliver drugs through the pulmonary route of administration. Although
the particle size between 100 and 500 nm is not represented in this table, it can be assumed that
most of the parameters discussed in the table holds true for this size range as well.
Since PNs and SLNs are formulated in nanosize ranges, it becomes critical to evaluate the
nanosize-related toxicity reported with different types of nanoparticles, such as inorganic and
metallic nanoparticles. Ferin et al. and Oberdorster et al. found that when rats were exposed to
