ABSTRACT
OBJECTIVE: Previously we showed that after intravenous injection a lipidic nanoemulsion concentrates in breast carcinoma tissue and other solid tumors and may carry drugs directed against neoplastic tissues. Use of the nanoemulsion decreases toxicity of the chemotherapeutic agents without decreasing the anticancer action. Currently, the hypothesis was tested whether the nanoemulsion concentrates in breast carcinoma tissue after locoregional injection. METHODS: Three different techniques of injection of the nanoemulsion were tested in patients scheduled for surgical treatment: G1 (n=4) into the mammary tissue 5 cm away from the tumor; G2 (n=4) into the peritumoral mammary tissue; G3 (n=6) into the tumoral tissue. The nanoemulsion labeled with radioactive cholesteryl oleate was injected 12 h before surgery; plasma decay of the label was determined from blood samples collected over 24 h and the tissue fragments excised during the surgery were analyzed for radioactivity uptake. RESULTS: Among the three nanoemulsion injection techniques, G3 showed the greatest uptake (data expressed in c.p.m/g of tissue) by the tumor (44,769+/-54,749) and by the lymph node (2356+/-2966), as well as the greatest concentration in tumor compared to normal tissue (844+/-1673). In G1 and G2, uptakes were, respectively, tumor: 60+/-71 and 843+/-1526; lymph node: 263+/-375 and 102+/-74; normal tissue: 139+/-102 and 217+/-413. CONCLUSIONS: Therefore, with intralesional injection of the nanoemulsion, a great concentration effect can be achieved. This injection technique may be thus a promising approach for drug-targeting in neoadjuvant chemotherapy in breast cancer treatment.
Subject(s)
Breast Neoplasms/metabolism , Cholesterol Esters/pharmacokinetics , Nanoparticles/administration & dosage , Adult , Aged , Aged, 80 and over , Breast Neoplasms/blood , Breast Neoplasms/drug therapy , Breast Neoplasms/surgery , Chemotherapy, Adjuvant , Cholesterol/administration & dosage , Cholesterol/blood , Cholesterol/chemistry , Cholesterol/pharmacokinetics , Cholesterol Esters/administration & dosage , Cholesterol Esters/chemistry , Emulsions/administration & dosage , Emulsions/chemistry , Emulsions/pharmacokinetics , Female , Humans , Injections, Intralesional , Middle Aged , Nanoparticles/chemistry , Neoadjuvant Therapy , Phosphatidylcholines/administration & dosage , Phosphatidylcholines/chemistry , Phosphatidylcholines/pharmacokinetics , Triglycerides/bloodABSTRACT
OBJECTIVE: Previously, it was shown that a lipidic emulsion (LDE) composed of phospholipids and cholesterol esters which binds to low-density lipoprotein (LDL) receptors may concentrate in acute myeloid leukemia cells. In this study, we aimed to verify whether LDE also has the ability to concentrate in malignant ovarian cancer after being injected into the blood circulation of the patients. METHODS: Three groups of women scheduled for surgery were included in the survey: 13 bearing malignant tumors, 9 with benign ovarian tumors, and 13 without ovarian tumor who were scheduled to undergo oophorectomy due to malignant disease of the uterine cervix or endometrium. On the day prior to surgery they were injected with LDE labeled with [(14)C]cholesteryl oleate. Specimens of tumors and normal ovaries excised during surgery were lipid extracted and analyzed for radioactivity counting. Results were expressed in radioactive count (cpm) per gram of tissue. RESULTS: The mean of the uptakes of the emulsion radioactivity by the malignant tumors was roughly eightfold greater when compared with that of the contralateral normal ovaries (2261 +/- 1444 and 275 +/- 137 cpm/g, respectively, P < 0.012), benign tumors, and normal ovaries of the patients without ovarian tumors. CONCLUSION: LDE has the ability to concentrate in malignant ovarian tumor tissue. Therefore, it can be used as a vehicle to direct cytotoxic drugs against malignant ovarian tumors, thus diminishing the side effects of chemotherapy.
