drug carriers in drug delivery systems. There have been many reviews about drug
carriers based on calixarenes [62–65]. Depending on the mechanism of delivery
implementation, we can generally classify them into the following three categories:
inclusion complexes, amphiphilic self-assembly, and supra-amphiphilic selfassembly.
Many research groups have reported drug delivery systems based on calixarenedrug complexes [62, 65, 66]. Typically, hydrophilic groups at the rim of calixarenes
have been widely utilized to produce water-soluble derivatives, which serve
as important containers to encapsulate drugs with poor water solubility in drug
delivery [67–70]. Pilar Ljpez-Còrnejo et al. constructed an inclusion complex
using p-sulfonatocalix[6]arene and doxorubicin [71]. The complex systems display
a preference for locating close to the DNA structure, facilitating the transport of
the antibiotic toward the polynucleotide, which means that they can act as an
excellent candidate for drug delivery. In addition, calixarenes in the solution partially
reduce the side effects of doxorubicin (DOX).
The calixarene amphiphiles can provide cavities for drug delivery by suitable
arrangement [72]. This highly attractive trait had prompted scientists to develop
new materials and devices that may be applied in bio-nanotechnology and nanomedicine [73]. The hydrophilic groups were usually modified at the upper rim of
calixarenes, and the lower rim was modified with hydrophobic groups such as linear
alkyl group with appropriate length to form stable supramolecular assemblies.
Longer alkyl groups usually cause extremely low solubility of amphiphiles and
aggregation in solid lipid nanoparticles. Casnati et al. have already extensively
reviewed the use of calixarene amphiphiles for nanocarrier applications in
drug delivery systems [73]. Zhao et al. synthesized a folic acid-PEG-modified
p-phosphonated calix[4]arene. By the calixarene self-assembly to form a nanocarrier, paclitaxel and carboplatin can be simultaneously delivered to tumor
cells at an optimal ratio (5:1, mol:mol), with potential synergy effect for ovarian
cancer [74]. Tao et al. used the self-assembly of amphiphilic calixarene as a carrier
for paclitaxel [74]. The encapsulation of paclitaxel using amphiphilic calixarene
was an attempt to improve the water solubility of the drug. The optimized formulation of paclitaxel-loaded amphiphilic calix[4]arene nanocapsules had an encapsulation efficiency of 82.65 Æ 2.54%. The paclitaxel-loaded calix[4]arene
formulation revealed improved paclitaxel-induced cytotoxicity in human cervical
cancer cell culture experiments in contrast to Taxol. Typically, Consoli et al. used a
polycationic calix[4]arene-based nanoaggregate entrapping curcumin by a
simple and reproducible method for delivering curcumin to anterior ocular tissues
(Fig. 14) [75]. The supramolecular assembly of calix[4]arene and curcumin was
a clear colloidal solution composed of micellar nanoaggregates in water.
The properties of the supramolecular assembly (such as size, polydispersity index,
surface potential, and drug loading percentage) all met the requirements for the
ocular drug delivery. In vitro and in vivo experiments, curcumin encapsulated
by calixarene has significantly enhanced solubility, increased stability, and improved
anti-inflammatory effects compared to free curcumin. Nanoassembly did
not affect the viability of J774A.1 macrophages and inhibited the expression of
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J. Gao and D.-S. Guo
carriers based on calixarenes [62–65]. Depending on the mechanism of delivery
implementation, we can generally classify them into the following three categories:
inclusion complexes, amphiphilic self-assembly, and supra-amphiphilic selfassembly.
Many research groups have reported drug delivery systems based on calixarenedrug complexes [62, 65, 66]. Typically, hydrophilic groups at the rim of calixarenes
have been widely utilized to produce water-soluble derivatives, which serve
as important containers to encapsulate drugs with poor water solubility in drug
delivery [67–70]. Pilar Ljpez-Còrnejo et al. constructed an inclusion complex
using p-sulfonatocalix[6]arene and doxorubicin [71]. The complex systems display
a preference for locating close to the DNA structure, facilitating the transport of
the antibiotic toward the polynucleotide, which means that they can act as an
excellent candidate for drug delivery. In addition, calixarenes in the solution partially
reduce the side effects of doxorubicin (DOX).
The calixarene amphiphiles can provide cavities for drug delivery by suitable
arrangement [72]. This highly attractive trait had prompted scientists to develop
new materials and devices that may be applied in bio-nanotechnology and nanomedicine [73]. The hydrophilic groups were usually modified at the upper rim of
calixarenes, and the lower rim was modified with hydrophobic groups such as linear
alkyl group with appropriate length to form stable supramolecular assemblies.
Longer alkyl groups usually cause extremely low solubility of amphiphiles and
aggregation in solid lipid nanoparticles. Casnati et al. have already extensively
reviewed the use of calixarene amphiphiles for nanocarrier applications in
drug delivery systems [73]. Zhao et al. synthesized a folic acid-PEG-modified
p-phosphonated calix[4]arene. By the calixarene self-assembly to form a nanocarrier, paclitaxel and carboplatin can be simultaneously delivered to tumor
cells at an optimal ratio (5:1, mol:mol), with potential synergy effect for ovarian
cancer [74]. Tao et al. used the self-assembly of amphiphilic calixarene as a carrier
for paclitaxel [74]. The encapsulation of paclitaxel using amphiphilic calixarene
was an attempt to improve the water solubility of the drug. The optimized formulation of paclitaxel-loaded amphiphilic calix[4]arene nanocapsules had an encapsulation efficiency of 82.65 Æ 2.54%. The paclitaxel-loaded calix[4]arene
formulation revealed improved paclitaxel-induced cytotoxicity in human cervical
cancer cell culture experiments in contrast to Taxol. Typically, Consoli et al. used a
polycationic calix[4]arene-based nanoaggregate entrapping curcumin by a
simple and reproducible method for delivering curcumin to anterior ocular tissues
(Fig. 14) [75]. The supramolecular assembly of calix[4]arene and curcumin was
a clear colloidal solution composed of micellar nanoaggregates in water.
The properties of the supramolecular assembly (such as size, polydispersity index,
surface potential, and drug loading percentage) all met the requirements for the
ocular drug delivery. In vitro and in vivo experiments, curcumin encapsulated
by calixarene has significantly enhanced solubility, increased stability, and improved
anti-inflammatory effects compared to free curcumin. Nanoassembly did
not affect the viability of J774A.1 macrophages and inhibited the expression of
220
J. Gao and D.-S. Guo