323
7.6 Cyclodextrin-Based Lipid Nanoparticles
Lipid-based cyclodextrin nanoparticles represent numerous examples such as liposomes, nanoemulsions, solid lipid nanoparticles, or nanostructured lipid carriers.
The association of cyclodextrin into lipid nanoparticle formulations not only promotes the hydrophobic drug loading within the aqueous components of the lipid
cyclodextrin nanoparticles but also maintains the targetability of nanoparticles. It
has been confirmed from earlier investigations that highly lipophilic molecules
included in the liposome membranes are released rapidly after in vivo administration (Maestrelli et al. 2005).
To ensure stable encapsulation, McCormack and Gregoriadis (1994a, b) suggested an approach wherein cyclodextrin/drug inclusion complexes are embedded
into liposomes. This strategy identified a novel drug delivery system consisting of
liposomes and cyclodextrin complexes of lipophilic drugs and designated as drugin- cyclodextrin-in-liposome. In liposomes, cyclodextrin complexation competes
with liposomal membrane binding, which strengthens the potential benefit of complexation in increasing hydrophobic drug retention. This concept was applied to
dexamethasone retinol and retinoic acid included in hydroxypropyl-β-cyclodextrin
(McCormack and Gregoriadis 1994a, b, 1996). Arima et al. (2006) developed
PEGylated liposomes entrapping the doxorubicin complex with γ-cyclodextrin and
evaluated the antitumor effect of doxorubicin in rodents bearing colon-26 tumor
cells. The findings of the study displayed retardation in tumor growth and an
increase in drug retention. From the historical point of view, a number of lipophilic
drugs have been encapsulated in the drug-in-cyclodextrin-in-liposome system. They
include Ca
2+
channel blocker drug nifedipine (Škalko et al. 1996); anti- inflammatory
drugs such as prednisolone (Fatouros et al. 2001), ketoprofen (Maestrelli et al.
2005), betamethasone (Piel et al. 2006), celecoxib (Jain et al. 2007), and indomethacin (Chen et al. 2007); anesthetic drugs such as benzocaine, butamben (Maestrelli
et al. 2010), and prilocaine (Bragagni et al. 2010); and anticancer drugs such as
ß-lapachone (Cavalcanti et al. 2011) and tretinoin (Ascenso et al. 2013).
Curcumin is well known for its therapeutic effects such as antibacterial, antiinflammatory, antioxidant, and antitumor. But, it exhibits instability and poor solubility. Therefore, to improve the cytotoxic effect and to resolve the issue of instability
and solubility, Dhule et al. (2012) fabricated curcumin-loaded cyclodextrin-based
liposomal nanoparticles and studied to treat osteosarcoma. The resulting
2-hydroxypropyl-γ-cyclodextrin/curcumin-liposome complex exhibits promising
cytotoxic potential and represents themselves as a potential delivery vehicle for the
treatment of cancers of different tissue origin.
Ji et al. (2016) practiced the use of cyclodextrin to enhance the tumor-targeting
ability of the lipid nanoparticles on the outside of the liposomal wall. The surface of
the liposome consisted of pirfenidone-loaded β-cyclodextrin linked with a cleavable
peptide, along with arginyl glycyl aspartic acid peptide (most common peptide
motif responsible for cell adhesion to the extracellular matrix) to target pancreatic
tumor cells, while the interior of the liposome carried the chemotherapeutic agent
7 Role of Cyclodextrins in Nanoparticle-Based Systems for Drug Delivery
7.6 Cyclodextrin-Based Lipid Nanoparticles
Lipid-based cyclodextrin nanoparticles represent numerous examples such as liposomes, nanoemulsions, solid lipid nanoparticles, or nanostructured lipid carriers.
The association of cyclodextrin into lipid nanoparticle formulations not only promotes the hydrophobic drug loading within the aqueous components of the lipid
cyclodextrin nanoparticles but also maintains the targetability of nanoparticles. It
has been confirmed from earlier investigations that highly lipophilic molecules
included in the liposome membranes are released rapidly after in vivo administration (Maestrelli et al. 2005).
To ensure stable encapsulation, McCormack and Gregoriadis (1994a, b) suggested an approach wherein cyclodextrin/drug inclusion complexes are embedded
into liposomes. This strategy identified a novel drug delivery system consisting of
liposomes and cyclodextrin complexes of lipophilic drugs and designated as drugin- cyclodextrin-in-liposome. In liposomes, cyclodextrin complexation competes
with liposomal membrane binding, which strengthens the potential benefit of complexation in increasing hydrophobic drug retention. This concept was applied to
dexamethasone retinol and retinoic acid included in hydroxypropyl-β-cyclodextrin
(McCormack and Gregoriadis 1994a, b, 1996). Arima et al. (2006) developed
PEGylated liposomes entrapping the doxorubicin complex with γ-cyclodextrin and
evaluated the antitumor effect of doxorubicin in rodents bearing colon-26 tumor
cells. The findings of the study displayed retardation in tumor growth and an
increase in drug retention. From the historical point of view, a number of lipophilic
drugs have been encapsulated in the drug-in-cyclodextrin-in-liposome system. They
include Ca
2+
channel blocker drug nifedipine (Škalko et al. 1996); anti- inflammatory
drugs such as prednisolone (Fatouros et al. 2001), ketoprofen (Maestrelli et al.
2005), betamethasone (Piel et al. 2006), celecoxib (Jain et al. 2007), and indomethacin (Chen et al. 2007); anesthetic drugs such as benzocaine, butamben (Maestrelli
et al. 2010), and prilocaine (Bragagni et al. 2010); and anticancer drugs such as
ß-lapachone (Cavalcanti et al. 2011) and tretinoin (Ascenso et al. 2013).
Curcumin is well known for its therapeutic effects such as antibacterial, antiinflammatory, antioxidant, and antitumor. But, it exhibits instability and poor solubility. Therefore, to improve the cytotoxic effect and to resolve the issue of instability
and solubility, Dhule et al. (2012) fabricated curcumin-loaded cyclodextrin-based
liposomal nanoparticles and studied to treat osteosarcoma. The resulting
2-hydroxypropyl-γ-cyclodextrin/curcumin-liposome complex exhibits promising
cytotoxic potential and represents themselves as a potential delivery vehicle for the
treatment of cancers of different tissue origin.
Ji et al. (2016) practiced the use of cyclodextrin to enhance the tumor-targeting
ability of the lipid nanoparticles on the outside of the liposomal wall. The surface of
the liposome consisted of pirfenidone-loaded β-cyclodextrin linked with a cleavable
peptide, along with arginyl glycyl aspartic acid peptide (most common peptide
motif responsible for cell adhesion to the extracellular matrix) to target pancreatic
tumor cells, while the interior of the liposome carried the chemotherapeutic agent
7 Role of Cyclodextrins in Nanoparticle-Based Systems for Drug Delivery