Cationic core-shell nanoparticles for intravesical chemotherapy in tumor-induced rat model: safety and efficacy.
Mitomycin C (MMC) has shown potent efficacy against a wide spectrum of cancers and is clinical first choice in superficial bladder tumors. However, intravesical chemotherapy with MMC has been ineffective due to periodical discharge of the bladder and instability of this drug in acidic pH, both resulting in high rate of tumor recurrence and insufficiency to prevent progression. Nanocarriers may be a promising alternative for prolonged, effective and safe intravesical drug delivery due to their favorable size, surface properties and optimum interaction with mucosal layer of the bladder wall. Hence, the aim of this study was to evaluate and optimize cationic core-shell nanoparticles formulations (based on chitosan (CS) and poly-ϵ-caprolactone (PCL)) in terms of antitumor efficacy after intravesical administration in bladder tumor induced rat model. Antitumor efficacy was determined through the parameters of survival rate and nanoparticle penetration into the bladder tissue. Safety of the formulations were evaluated by histopathological evaluation of bladder tissue as well as observation of animals treated with MMC bound to nanoparticles. Results indicated that chitosan coated poly-ϵ-caprolactone (CS-PCL) nanoparticles presented the longest survival rate among all treatment groups as evaluated by Kaplan-Meier plotting. Histopathological evaluation revealed that cationic nanoparticles were localized and accumulated in the bladder tissue. As intravesical chemotherapy is a local therapy, no MMC was quantified in blood after intravesical instillation indicating no systemic uptake for the drug which could have subsequently led to side effects. In conclusion, core-shell type cationic nanoparticles may be effective tools for the intravesical chemotherapy of recurrent bladder tumors.
Hacettepe University Faculty of Pharmacy, Department of Pharmaceutical Technology, Sıhhiye-Ankara 06100, Turkey. Electronic address: nerdogar@hacettepe.edu.tr.
Nazlı
N
Erdogar
Hacettepe University Faculty of Medicine, Department of Pharmacology, Sıhhiye-Ankara 06100, Turkey. Electronic address: alperi@hacettepe.edu.tr.
Alper B
AB
İskit
Hacettepe University Faculty of Pharmacy, Department of Pharmaceutical Technology, Sıhhiye-Ankara 06100, Turkey.
Hakan
H
Eroglu
Hacettepe University Faculty of Medicine, Department of Anatomy, Sıhhiye-Ankara 06100, Turkey. Electronic address: mfsargon@hacettepe.edu.tr.
Mustafa F
MF
Sargon
Bülent Ecevit University, Faculty of Medicine, Department of Urology, Kozlu-Zonguldak 67600, Turkey. Electronic address: amungan@yahoo.com.
N Aydın
NA
Mungan
Hacettepe University Faculty of Pharmacy, Department of Pharmaceutical Technology, Sıhhiye-Ankara 06100, Turkey. Electronic address: eremino@hacettepe.edu.tr.
Erem
E
Bilensoy
D000283:Administration, Intravesical; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002085:Butylhydroxybutylnitrosamine / Q000633:toxicity; D002412:Cations; D048271:Chitosan / Q000737:chemistry; D018572:Disease-Free Survival; D004337:Drug Carriers / Q000737:chemistry*; D053208:Kaplan-Meier Estimate; D008297:Male; D016685:Mitomycin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D053758:Nanoparticles / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D000903:Antibiotics, Antineoplastic; D002412:Cations; D004337:Drug Carriers; D011091:Polyesters; C016240:polycaprolactone; D002085:Butylhydroxybutylnitrosamine; D016685:Mitomycin; D048271:Chitosan
Bladder cancer; Cationic nanoparticles; Chitosan; Core-shell; Mitomycin C; Poly-ϵ-caprolactone