Role of Nanoparticles in the Treatment of Noninvasive Bladder Cancer

WOS: 000219415200013Bladder cancer is the ninth most common cancer types in the world and transitional bladder cancer constitutes 90% of all bladder cancer neoplasms depending on cancer cell morphology. Clinical choice of treatment is transurethral resection (TUR), after which the recurrence rate is 50-80% and the tumor has a 14% chance of progression. To avoid recurrence and progression, adjuvant intravesical chemotherapy or immunotherapy is required. Intravesical drug delivery has many advantages. Bladder allows manipulation since it is easily accessible and a closed area, allows catheterization rendering this organ to be an advantageous site for localized drug delivery. Drugs are administered into urinary bladder directly resulting in greater exposure of tissues to drug. On the other hand, because of periodical discharge, rapid drug dilution necessitates repeated catheterization and results in loss of drug efficacy. Another disadvantage is the very low permeability of urothelium. Urothelium limits the absorption of molecules into the systemic circulation and prevent adherence of foreign agents on the urothelial surface exerting the same effect of drugs and drug delivery systems. To overcome these problems, nanotechnological approach in the biomedical field seems promising and in this frame new drug carrier systems were focused and bioadhesive nanoparticles were developed. Nanoparticles are submicron, solid, colloidal particles in a size ranging between 10 to 1000 nm. Nanoparticles are generally prepared from biodegradable polymers with specific physicochemical properties and are loaded with active molecules to act as drug delivery systems. Bioadhesive nanoparticles allow prolonged residence time of drug in the mucosal tissues such as bladder wall and can be promising to pass the bladder permeability barrier. Due to their particle size and surface charge, they sustain the drug release at cancerous tissues and protect the drug from acidic urine pH and other degradation factors such as hydrolysis and photodegradation. In addition, nanoparticulate carriers form a drug reservoir in the action site to reduce drug loss and to improve drug efficacy. In this study, we aim to review the role and application of nanoparticles in noninvasive bladder tumors with current literature

Prolonged retention and in vivo evaluation of cationic nanoparticles loaded with Mitomycin C designed for intravesical chemotherapy of bladder tumours

WOS: 000307999000008PubMed: 22468630To overcome the recurrence problem in bladder tumours; nanoparticles with positive surface charge may improve interaction with biological membranes for intravesical administration. The aim of this study was to design, develop and evaluate (in vitro-in vivo) cationic nanoparticles based on chitosan, poly-L-lysine or polycaprolactone for the effective intravesical delivery of chemotherapeutic agent MMC in a rat model. Poly-L-lysine-coated polycaprolactone nanoparticles and chitosan-coated polycaprolactone nanoparticles were prepared by the double emulsion technique. Chitosan nanoparticles were prepared by ionic gelation. It was found that nanoparticle formulations of 160-320nm in size can be produced in 14-35% encapsulation efficiency. Variability in the particle size of nanoparticles depended on the preparation method. Encapsulation was increased by two-fold for CS-PCL as a result of the double emulsion technique. Commercial MMC product in solution form and cationic nanoparticle formulations were compared for in vivo bladder retention properties and effect of formulations on urine volume.TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [109S172]; Turkish Academy of SciencesTurkish Academy of Sciences [EA-TUBA-GEBIP/2001-2-11]Authors would like to acknowledge that this project was financially supported by TUBITAK (Scientific Research Project Number: 109S172). Alper B. Iskit has been supported by the Turkish Academy of Sciences, in the framework of the Young Scientist Award Program (EA-TUBA-GEBIP/2001-2-11)

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-µ-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-µ-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. © 2014 Elsevier B.V.109S172 EA-TUBA-GEBIP/2001-2-11Authors would like to acknowledge TUBITAK Scientific Research Project ( 109S172 ) for financial support of this study. Alper B. Iskit has been supported by the Turkish Academy of Sciences , in the framework of the Young Scientist Award Program ( EA-TUBA-GEBIP/2001-2-11 )