Biodistribution of antisense nanoparticles in mammary carcinoma rat model.
Efficient and specific delivery of antisenses (ASs) and protection of the sequences from degradation are critical factors for effective therapy. Sustained release nanoparticles (NP) offer increased resistance to nuclease degradation, increased amounts of AS uptake, and the possibility of control in dosing and sustained duration of AS administration. The biodegradable and biocompatible poly(D,L-lactic-co-glycolic acid) copolymer (PLGA) was utilized to encapsulate AS directed against osteopontin (OPN), which is a promising therapeutic target in mammary carcinoma. Whole body biodistribution of OPN AS NP was evaluated in comparison to naked AS, in intact and mammary carcinoma metastasis model bearing rats. Naked and NP encapsulated AS exhibited different biodistribution profiles. AS NP, in contrast to naked AS, tended to accumulate mostly in the spleen, liver, and at the tumor inoculation site. Drug levels in intact organs were negligible. The elimination of naked AS was faster, due to rapid degradation of the unprotected sequence. It is concluded that AS NP protect the AS from degradation, provide efficient AS delivery to the tumor tissue, and minimize AS accumulation in intact organs due to the AS sustained release profile as well as the favorable NP physicochemical properties.
Elazar
Victoria
V
School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
Adwan
Hassan
H
Rohekar
Keren
K
Zepp
Michael
M
Lifshitz-Shovali
Rinat
R
Berger
Martin R
MR
Golomb
Gershon
G
D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D016375:Antisense Elements (Genetics) / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy / Q000556:secondary / Q000652:urine; D002277:Carcinoma / Q000097:blood / Q000188:drug therapy / Q000556:secondary / Q000652:urine; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers / Q000032:analysis / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000032:analysis / Q000737:chemistry / Q000627:therapeutic use; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000097:blood / Q000188:drug therapy / Q000652:urine; D053758:Nanoparticles / Q000032:analysis / Q000737:chemistry* / Q000627:therapeutic use; D053495:Osteopontin / Q000235:genetics; D010316:Particle Size; D011100:Polyglycolic Acid / Q000032:analysis / Q000737:chemistry / Q000627:therapeutic use; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D011923:Rats, Nude; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D000970:Antineoplastic Agents; D016375:Antisense Elements (Genetics); D003692:Delayed-Action Preparations; D004337:Drug Carriers; D053495:Osteopontin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid