416
R. Mankamna Kumari et al.
plethora of polymers and inorganic metals available for synthesis of NPs, polyhydroxyalkanoates (PHA), poly-lactide-co-glycolide (PLGA) and cyclodextrins are
widely used for NPs development. On the other hand, silver, gold, carbon nanotubes,
and quantum dots are widely investigated in the field of inorganic nanoparticle synthesis for therapeutic process. However, there are certain challenges faced during NPs
development, regarding characterization, safety, and manufacturability. The drugs
would be ineffective if it degrades within NPs or not released in a controlled manner;
this might also lead to toxicity as well as non-specificity. Thus, a complete understanding of size, formulation, composition, toxicity, reactivity, and biodegradability
is required to bring nanoformulations to bring it to the clinical level.
2 Characteristics of NPs for Drug Delivery
As discussed earlier, the cellular uptake and pharmacokinetics of the NPs depends
mainly on several characteristics of NPs such as size, shape, surface charge, drug
loading, and release.
2.1 Effect of Size on Drug Delivery
The size of NPs dictates the toxicity, targetability, and distribution of the drugs
(Fig. 3). It has been reported that NPs of size around 100 nm can exhibit 2.5-fold
greater uptake than NPs of size range of 1 μm and sixfold greater uptake than 10 μm
(Desai et al. 1997). As discussed previously, the major obstacles in drug delivery are
rapid clearance of NPs from circulatory system by mononuclear phagocyte system
and reticuloendothelial system, which can be prevented by tuning the size of NPs.
Also, the size of the NPs has known to influence the cellular uptake by the cells
by changing enthalpic and entropic properties that affect the adhesion properties of
the cellular receptors and NPs (Elias et al. 2013). Other studies also showed sizedependent uptake. Zhang et al. synthesized ligand coated NPs of size 50 nm that
exhibited efficient uptake. Similarly, mesoporous silica NPs developed in the range
of 50 nm showed highest uptake by the cells. Also, gold NPs at a size range of 50 nm
showed highest uptake in the SKBR-3 cells (Jiang et al. 2008b; Lu et al. 2009; Zhang
et al. 2009). Also, endocytosis requires membrane-wrapping process, which becomes
feasible with decreased size of particles. Thus, NPs carrying small number of ligands
on the surface can easily bind to the receptors. It is to be noted that enthalpic limit for
most of the spherical NPs is supposed to be around 30 nm, which indicates that NPs of
size less than this will not drive membrane-wrapping process to permit endocytosis
to occur effectively (Albanese et al. 2012; Yuan et al. 2010; Zhang et al. 2009).
Contrastingly, it was observed that gold NPs coated with Herceptin of size range
between 2 and 100 nm showed good cellular uptake in relative to non-coated NPs.
Besides size of the NPs, other factors affecting the receptor mediated uptake of NPs
R. Mankamna Kumari et al.
plethora of polymers and inorganic metals available for synthesis of NPs, polyhydroxyalkanoates (PHA), poly-lactide-co-glycolide (PLGA) and cyclodextrins are
widely used for NPs development. On the other hand, silver, gold, carbon nanotubes,
and quantum dots are widely investigated in the field of inorganic nanoparticle synthesis for therapeutic process. However, there are certain challenges faced during NPs
development, regarding characterization, safety, and manufacturability. The drugs
would be ineffective if it degrades within NPs or not released in a controlled manner;
this might also lead to toxicity as well as non-specificity. Thus, a complete understanding of size, formulation, composition, toxicity, reactivity, and biodegradability
is required to bring nanoformulations to bring it to the clinical level.
2 Characteristics of NPs for Drug Delivery
As discussed earlier, the cellular uptake and pharmacokinetics of the NPs depends
mainly on several characteristics of NPs such as size, shape, surface charge, drug
loading, and release.
2.1 Effect of Size on Drug Delivery
The size of NPs dictates the toxicity, targetability, and distribution of the drugs
(Fig. 3). It has been reported that NPs of size around 100 nm can exhibit 2.5-fold
greater uptake than NPs of size range of 1 μm and sixfold greater uptake than 10 μm
(Desai et al. 1997). As discussed previously, the major obstacles in drug delivery are
rapid clearance of NPs from circulatory system by mononuclear phagocyte system
and reticuloendothelial system, which can be prevented by tuning the size of NPs.
Also, the size of the NPs has known to influence the cellular uptake by the cells
by changing enthalpic and entropic properties that affect the adhesion properties of
the cellular receptors and NPs (Elias et al. 2013). Other studies also showed sizedependent uptake. Zhang et al. synthesized ligand coated NPs of size 50 nm that
exhibited efficient uptake. Similarly, mesoporous silica NPs developed in the range
of 50 nm showed highest uptake by the cells. Also, gold NPs at a size range of 50 nm
showed highest uptake in the SKBR-3 cells (Jiang et al. 2008b; Lu et al. 2009; Zhang
et al. 2009). Also, endocytosis requires membrane-wrapping process, which becomes
feasible with decreased size of particles. Thus, NPs carrying small number of ligands
on the surface can easily bind to the receptors. It is to be noted that enthalpic limit for
most of the spherical NPs is supposed to be around 30 nm, which indicates that NPs of
size less than this will not drive membrane-wrapping process to permit endocytosis
to occur effectively (Albanese et al. 2012; Yuan et al. 2010; Zhang et al. 2009).
Contrastingly, it was observed that gold NPs coated with Herceptin of size range
between 2 and 100 nm showed good cellular uptake in relative to non-coated NPs.
Besides size of the NPs, other factors affecting the receptor mediated uptake of NPs