Back to Search
Start Over
Gemcitabine hydrochloride microspheres used for intravesical treatment of superficial bladder cancer: a comprehensive in vitro/ex vivo/in vivo evaluation.
- Source :
-
Drug design, development and therapy [Drug Des Devel Ther] 2018 Jul 02; Vol. 12, pp. 1959-1975. Date of Electronic Publication: 2018 Jul 02 (Print Publication: 2018). - Publication Year :
- 2018
-
Abstract
- Introduction: Bladder cancer is responsible for more than 130,000 deaths annually worldwide. Intravesical delivery of chemotherapeutic agents provides effective drug localization to the target area to reduce toxicity and increase efficacy. This study aimed to develop an intravesical delivery system of gemcitabine HCl (Gem-HCl) to provide a sustained-release profile, to prolong residence time, and to enhance its efficiency in the treatment of bladder cancer.<br />Materials and Methods: For this purpose, bioadhesive microspheres were successfully prepared with average particle size, encapsulation efficiency, and loading capacity of 98.4 µm, 82.657%±5.817%, and 12.501±0.881 mg, respectively. For intravesical administration, bioadhesive microspheres were dispersed in mucoadhesive chitosan or in situ poloxamer gels and characterized in terms of gelation temperature, viscosity, mechanical, syringeability, and bioadhesive and rheological properties. The cytotoxic effects of Gem-HCl solution, Gem-HCl microspheres, and Gem-HCl microsphere-loaded gel formulations were evaluated in two different bladder cancer cell lines: T24 (ATCC HTB4TM) and RT4 (ATCC HTB2TM).<br />Results: According to cell-culture studies, Gem-HCl microsphere-loaded poloxamer gel was more cytotoxic than Gem-HCl microsphere-loaded chitosan gel. Antitumor efficacy of newly developed formulations were investigated by in vivo studies using bladder-tumor-induced rats.<br />Conclusion: According to in vivo studies, Gem-HCl microsphere-loaded poloxamer gel was found to be an effective and promising alternative for current intravesical delivery-system therapies.<br />Competing Interests: Disclosure The authors report no conflicts of interest in this work.
- Subjects :
- Administration, Intravesical
Animals
Antimetabolites, Antineoplastic chemistry
Cell Line, Tumor
Deoxycytidine administration & dosage
Deoxycytidine chemistry
Deoxycytidine therapeutic use
Drug Compounding
Humans
In Vitro Techniques
Microscopy, Electron, Scanning
Neoplasms, Experimental drug therapy
Neoplasms, Experimental pathology
Particle Size
Rats
Rats, Sprague-Dawley
Rheology
Urinary Bladder Neoplasms pathology
Viscosity
Gemcitabine
Antimetabolites, Antineoplastic administration & dosage
Antimetabolites, Antineoplastic therapeutic use
Deoxycytidine analogs & derivatives
Microspheres
Urinary Bladder Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1177-8881
- Volume :
- 12
- Database :
- MEDLINE
- Journal :
- Drug design, development and therapy
- Publication Type :
- Academic Journal
- Accession number :
- 29997433
- Full Text :
- https://doi.org/10.2147/DDDT.S164704