250
DU145 and PC-3 and the androgen-sensitive model
LNCaP. Camptothecin-loaded nanosponges (CAM-NSs) inhibited topoisomerase I activity, and induced DNA damage and cell
cycle arrest more effectively than CAM. Annexin V/propidium
iodide staining showed an induction of cell death at low concentrations that were not effective for CAM but CAM-NSs still exerted
higher antiproliferative activity than CAM. Results demonstrated
the higher antitumor effectiveness of CAM-NSs compared to
CAM in prostate cancer cells [28].
Moreover, the increased antiangiogenic activity of CAM-NSs,
together with the increased antiproliferative activity, may explain
the strikingly different antitumor effectiveness of CAM-NSs and
free CAM. This difference may be ascribed to the deterred hydrolysis of the active drug and to CAM-NS accumulation in the tumor
due to the EPR effect dependent on the leaky vasculature and poor
lymphatic drainage of the tumor microenvironment. In vivo experiments notably could not detect the potentially increased antimetastatic activity of CAM-NSs due to the inhibitory activity on
tumor cell adhesion [29].
Further studies showed enhanced cytotoxic effect of CAMNSs in anaplastic thyroid cancer (ATC) on orthotropic xenograft
tumors. Results showed that CAM-NSs inhibited the growth of
ATC cell lines both in vitro and in vivo to a higher extent than free
CAM, and also inhibited tumor cell adhesion to endothelial cells
and migration which suggest effectiveness to inhibit tumor metastatic dissemination, supporting relevance use of CAM-NSs to
deliver anticancer drugs in vivo [30].
Tamoxifen is a low-dose therapeutic agent belonging to a class
of drugs called selective estrogen receptor modulators which have
both estrogenic and antiestrogenic effects, used for the treatment
of both early and advanced ER+ (estrogen receptor positive) breast
cancer in pre- and postmenopausal women and typically given to
patients for long periods of time [31]. Tamoxifen’s low water solubility limits its therapeutic application and calls for a stable nanocarrier which controls the rate of drug release. Tamoxifen
nanosponge complexes (TNC) from β-cyclodextrin NS crosslinked by carbonyldiimidazole (ratios 1:2, 1:4, and 1:8) were
obtained by freeze-drying method. Differential scanning calorimetry, Fourier transformed infrared spectroscopy, and X-ray powder
diffraction studies confirmed tamoxifen complexation within
NS. The area under the curve (AUC) and maximum concentration
(C max ) of TNC formulation (1236.4 ± 16.12 μg h/mL h,
421.156 ± 0.91 μg/mL) after gastric intubation were higher (1.4fold) than plain drug. Cytotoxic studies on MCF-7 cells showed
that TNC formulation was more cytotoxic than plain tamoxifen
after 24 and 48 h of incubation [31].
Temozolomide (TMZ), second-generation imidazotetrazine
prodrug that undergoes spontaneous conversion under physiologiMaria Tannous et al.
DU145 and PC-3 and the androgen-sensitive model
LNCaP. Camptothecin-loaded nanosponges (CAM-NSs) inhibited topoisomerase I activity, and induced DNA damage and cell
cycle arrest more effectively than CAM. Annexin V/propidium
iodide staining showed an induction of cell death at low concentrations that were not effective for CAM but CAM-NSs still exerted
higher antiproliferative activity than CAM. Results demonstrated
the higher antitumor effectiveness of CAM-NSs compared to
CAM in prostate cancer cells [28].
Moreover, the increased antiangiogenic activity of CAM-NSs,
together with the increased antiproliferative activity, may explain
the strikingly different antitumor effectiveness of CAM-NSs and
free CAM. This difference may be ascribed to the deterred hydrolysis of the active drug and to CAM-NS accumulation in the tumor
due to the EPR effect dependent on the leaky vasculature and poor
lymphatic drainage of the tumor microenvironment. In vivo experiments notably could not detect the potentially increased antimetastatic activity of CAM-NSs due to the inhibitory activity on
tumor cell adhesion [29].
Further studies showed enhanced cytotoxic effect of CAMNSs in anaplastic thyroid cancer (ATC) on orthotropic xenograft
tumors. Results showed that CAM-NSs inhibited the growth of
ATC cell lines both in vitro and in vivo to a higher extent than free
CAM, and also inhibited tumor cell adhesion to endothelial cells
and migration which suggest effectiveness to inhibit tumor metastatic dissemination, supporting relevance use of CAM-NSs to
deliver anticancer drugs in vivo [30].
Tamoxifen is a low-dose therapeutic agent belonging to a class
of drugs called selective estrogen receptor modulators which have
both estrogenic and antiestrogenic effects, used for the treatment
of both early and advanced ER+ (estrogen receptor positive) breast
cancer in pre- and postmenopausal women and typically given to
patients for long periods of time [31]. Tamoxifen’s low water solubility limits its therapeutic application and calls for a stable nanocarrier which controls the rate of drug release. Tamoxifen
nanosponge complexes (TNC) from β-cyclodextrin NS crosslinked by carbonyldiimidazole (ratios 1:2, 1:4, and 1:8) were
obtained by freeze-drying method. Differential scanning calorimetry, Fourier transformed infrared spectroscopy, and X-ray powder
diffraction studies confirmed tamoxifen complexation within
NS. The area under the curve (AUC) and maximum concentration
(C max ) of TNC formulation (1236.4 ± 16.12 μg h/mL h,
421.156 ± 0.91 μg/mL) after gastric intubation were higher (1.4fold) than plain drug. Cytotoxic studies on MCF-7 cells showed
that TNC formulation was more cytotoxic than plain tamoxifen
after 24 and 48 h of incubation [31].
Temozolomide (TMZ), second-generation imidazotetrazine
prodrug that undergoes spontaneous conversion under physiologiMaria Tannous et al.