Targeted Drug Delivery - Nanomaterials for Medical Applications - page 186

(Desai et al., 1997) 223 . In another study, NPs were shown to penetrate through-
out the submucosal layers of a rat intestinal loop model, while the micropar-
ticles were localized in the epithelial lining. 53 Thus, the particle distribution in
cells can partly be tuned by controlling particle size.
5.4 DRUG LOADING
Incorporation of a drug on or in an NM is referred to as drug loading. An ideal
NMs' drug delivery system should have a high drug-loading capacity without
aggregation. High drug loading capacity can minimize administration or the
number of doses. Dispersibility is needed for smooth and efficient delivery of
the drugs.
Drug loading can be accomplished in several ways; however, drug loading
and entrapment efficiency depend on drug solubility in the NMs, dispersion
medium, the NMs' size and composition, drug molecular weight (MW) and sol-
ubility, drug-NM interaction, and/or the presence of surface functional groups
(i.e. carboxyl, amine, ester, etc) on either the drugs or on the NMs. 54,55,56,57,58,59
Some NM formulations use PEG because it has little or no effect on drug
loading and interactions. 60 Additionally, biomolecules, drugs, or proteins encap-
sulated in NPs show the greatest loading efficiency when they are loaded at or
near their isoelectric point (pI). 61 For small molecules, studies show that the use
of ionic interaction between the drug and matrix materials can be very effective
in increasing drug loading. 62 , 63
Drug incorporation and loading capacity is a very important point to judge the
suitability of a drug carrier system. The loading capacity is generally expressed
in percent related to the NP. Westesen et al. 64 reported the incorporation of drugs
using loading capacities of typically 1-5%, for ubidecarenone loading capaci-
ties of up to 50% while Iscan and coworkers 65,66 reported 10-20% for tetracaine
and etomidate.
Depending upon the nature of the NM and the drug, loading may be done in
several ways. The drug can be loaded on the NM surface through charge-charge
interaction, covalent bonding, or through HI. It can also be loaded inside the
NM core through HI or encapsulation during the NM synthesis. Examples of
these methods are given below.
The protocols described below use general conditions that need to be opti-
mized for each situation. The adsorption/absorption methods call for absorption
of the drug after NP formation; this is achieved by incubating the NM with a
concentrated drug solution. Furthermore, the protocols are recommended for
research use only and not for clinical or human use.
It must be noted that partitioning effects of the drug between the melted
lipid phase and the aqueous surfactant phase can occur during drug-NP pro-
duction. 67 During the hot homogenization technique, the drug partitions from
the liquid oil phase to the aqueous water phase such that the amount in the
water phase increases with the solubility of the drug in the water phase which