Coadministration of doxorubicin and etoposide loaded in camel milk phospholipids liposomes showed increased antitumor activity in a murine model.
Small unilamellar vesicles from camel milk phospholipids (CML) mixture or from 1,2 dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) were prepared, and anticancer drugs doxorubicin (Dox) or etoposide (ETP) were loaded. Liposomal formulations were used against fibrosarcoma in a murine model. Results showed a very high percentage of Dox encapsulation (~98%) in liposomes (Lip) prepared from CML-Lip or DPPC-Lip, whereas the percentage of encapsulations of ETP was on the lower side, 22% of CML-Lip and 18% for DPPC-Lip. Differential scanning calorimetry curves show that Dox enhances the lamellar formation in CML-Lip, whereas ETP enhances the nonlamellar formation. Differential scanning calorimetry curves also showed that the presence of Dox and ETP together into DPPC-Lip produced the interdigitation effect. The in vivo anticancer activity of liposomal formulations of Dox or ETP or a combination of both was assessed against benzopyrene (BAP)-induced fibrosarcoma in a murine model. Tumor-bearing mice treated with a combination of Dox and ETP loaded into CML-Lip showed increased survival and reduced tumor growth compared to other groups, including the combination of Dox and ETP in DPPC-Lip. Fibrosarcoma-bearing mice treated with a combination of free (Dox + ETP) showed much higher tumor growth compared to those groups treated with CML-Lip-(Dox + ETP) or DPPC-Lip-(Dox + ETP). Immunohistochemical study was also performed to show the expression of tumor-suppressor PTEN, and it was found that the tumor tissues from the group of mice treated with a combination of free (Dox + ETP) showed greater loss of cytoplasmic PTEN than tumor tissues obtained from the groups of mice treated with CML-Lip-(Dox + ETP) or DPPC-Lip-(Dox + ETP).
Department of Pharmaceutics, College of Pharmacy, Qassim University, Buraydah, Kingdom of Saudi Arabia.
Hamzah M
HM
Maswadeh
Department of Pharmaceutics, College of Pharmacy, Qassim University, Buraydah, Kingdom of Saudi Arabia.
Ahmed N
AN
Aljarbou
Department of Pharmacology and Therapeutics, College of Medicine, Qassim University, Buraydah, Kingdom of Saudi Arabia.
Mohammed S
MS
Alorainy
College of Applied Medical Sciences, Qassim University, Buraydah, Kingdom of Saudi Arabia.
Arshad H
AH
Rahmani
College of Applied Medical Sciences, Qassim University, Buraydah, Kingdom of Saudi Arabia.
Masood A
MA
Khan
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002152:Calorimetry, Differential Scanning; D002162:Camelus; D002626:Chemistry, Pharmaceutical; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000473:pathology; D007124:Immunoenzyme Techniques; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008892:Milk / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D012513:Sarcoma, Experimental / Q000188:drug therapy* / Q000473:pathology
D008081:Liposomes; D010743:Phospholipids; D015060:1,2-Dipalmitoylphosphatidylcholine; D005047:Etoposide; D004317:Doxorubicin
BAP-induced tumors; combination chemotherapy; immunohistochemistry