Introduction - Lipid Nanoparticles: Production, Characterization and Stability - page 2

1.1 The Rationale of Introducing Colloidal Carriers
Despite great success in the lead optimization programmes, highly lipophilic drug
candidates are the major outcomes of such critical drug discovery drives (Porter
et al. 2007 ). Although many of these drug candidates have exceptional in vitro
potency, lack of significant solubility in water often presents challenges such as
(Merisko-Liversidge and Liversidge 2008 ):
• Poor bioavailability.
• Variations in bioavailability when in fed or fasted state.
• Use of excipients such as co-solvents to improve water solubility may prove to
be harsh.
• Drug precipitation after dosing.
• Patient non-compliance.
In recent years, the proportion of such insoluble drug candidates has been esti-
mated to be roughly 70 % of new drug discoveries. In addition, about 40 % of
currently marketed immediate-release oral drugs are practically water-insoluble
(Kawabata et al. 2011 ).
Poor water solubility of drugs limits the development of formulations deliver-
able by oral and parenteral routes. Formulation strategies that have been reported
to overcome solubility issues such include size reduction, complexation and solu-
bilisation in surfactant solutions, pro-drug design, derivatization and modulation
of crystallinity (Bikiaris 2011 ). A more recent and successful strategy to improve
solubility is drug encapsulation. Encapsulation of drugs in a colloidal carrier sys-
tem protects the drug from biological degradation, aids in modulation of release
kinetics and modifies its biodistribution (Bunjes and Siekmann 2005 ).
1.2 Introduction to Colloidal Drug Carriers
The introduction of colloidal systems has led to a revolution in the field of thera-
peutics over the last couple of decades. It has now been established that the use of
colloidal drug carriers in drug delivery not only improves the therapeutic index,
but also reduces associated side effects. Colloidal drug carriers have been used
to achieve the most optimized therapeutic outcomes (Jaafar-Maalej et al. 2012 ).
There is increasing optimism that colloidal drug carriers will elicit significant and
innovative benefits in early diagnosis, prevention and control of disease. A broad
variety of colloidal drug carriers have been introduced to address the challenge of
solubilisation of poorly soluble drugs (Westesen 2000 ), and based on the mate-
rial used in their preparation, they are categorized as polymer-based or lipid-based
systems.
Polymeric nanoparticles are colloidal carriers composed of biodegradable mac-
romolecular polymers. Emulsion polymerization is a well-established production