Introduction - Lipid Nanoparticles: Production, Characterization and Stability - page 3

method, but involves the use of toxicologically harmful reactive cross-linkers and
carcinogenic monomers. Complete removal of these constituents is a difficult
task (Reis et al. 2006 ). Moreover, slow degradation of the polymer results in its
accumulation and may produce toxic metabolites (Bunjes and Siekmann 2005 ).
Polymeric injectable depot formulations such as Lupron ® (leuprolide), Nutropin ®
(recombinant human growth hormone), Sandostatin ® (octreotide), Decapeptyl ®
(triptorelin) and Parlodel ® (bromocriptine) are being marketed in spite of these
limitations.
Lipid-based colloidal carriers have been introduced to overcome the toxicologi-
cal issues exhibited by polymeric systems. Prominent research has been carried
out on lipidic systems including liposomes, nanoemulsions, micelles, cubosomes
and lipid nanoparticles. Liposomes, considered to be the first drug carriers, were
described in the early twentieth century. However, it was only in the latter half of
the century that they were introduced as drug carriers. Successful development of
intravenous liposomal formulations such as Doxyl ® and Caelyx ® (both liposomal
doxorubicin), DaunoXome ® (liposomal daunorubicin), AmBisome ® (liposomal
amphotericin B) and dermal formulation such as “Capture” have demonstrated the
usefulness of liposomes as lipidic drug carriers. There are, however, some draw-
backs associated with the storage stability of the liposomes. Incorporation of a
drug into the phospholipid bilayer can decrease the carrier stability. Additional
limitations associated with large scale manufacturing and sterilization after pro-
duction also make commercialisation of liposomes difficult (de Mendoza et al.
2010 ).
Parenteral emulsions have been used as calorie sources for decades (Waitzberg
et al. 2006 ). These systems are produced in large quantities and also exhibit long-
term stability. Due to these advantages, lipid emulsions are becoming popular
as drug carriers. Several drug-loaded colloidal emulsions such as Daizemuls ® /
Diazepam-Lipuro ® (diazepam), Liple ® (alprostadil), Diprivan ® (propofol),
Limethason ® (dexamethasone palmitate), Lipo-NSAID ® /Ropion ® (flurbiprofen
axetil) and Etomidat-lipuro ® (etomidate) are currently available on the market.
Lipid emulsions are, however, not without their shortcomings. Drug molecules
that have high mobility in the liquid oil droplet may diffuse out of the droplet,
disturbing the stabilizing surfactant film. These effects can cause mechanical or
electrochemical instability (such as film rupture, reduction in film elasticity or
modification of the zeta potential). This, in turn, can induce coalescence or par-
ticle growth (Washington 1996 ). The high mobility of drug molecules within the
emulsion droplets allows for quick equilibration in the aqueous phase, a phenom-
enon called “drug leakage”, and causes rapid release of drugs. This limits the use
of lipid emulsions as sustained-release formulations (Magenheim et al. 1993 ;
Washington 1996 ).
The use of solid lipids was introduced to lower drug mobility observed with
liquid lipids. Reduction in mobility inhibits drug leakage and also counteracts
drug migration into the emulsifier film. The solid core of the colloidal carrier pro-
vides better physicochemical stability. A few of the advantages that the solid lipid
imparts to the carrier system are outlined in Table 1.1 .