Design and evaluation of an intravesical delivery system for superficial bladder cancer: preparation of gemcitabine HCl-loaded chitosan-thioglycolic acid nanoparticles and comparison of chitosan/poloxamer gels as carriers.
This study aimed to develop an intravesical delivery system of gemcitabine HCl for superficial bladder cancer in order to provide a controlled release profile, to prolong the residence time, and to avoid drug elimination via urination. For this aim, bioadhesive nanoparticles were prepared with thiolated chitosan (chitosan-thioglycolic acid conjugate) and were dispersed in bioadhesive chitosan gel or in an in situ gelling poloxamer formulation in order to improve intravesical residence time. In addition, nanoparticle-loaded gels were diluted with artificial urine to mimic in vivo conditions in the bladder and were characterized regarding changes in gel structure. The obtained results showed that chitosanthioglycolic acid nanoparticles with a mean diameter of 174.5±3.762 nm and zeta potential of 32.100±0.575 mV were successfully developed via ionotropic gelation and that the encapsulation efficiency of gemcitabine HCl was nearly 20%. In vitro/ex vivo characterization studies demonstrated that both nanoparticles and nanoparticle-loaded chitosan and poloxamer gels might be alternative carriers for intravesical administration of gemcitabine HCl, prolonging its residence time in the bladder and hence improving treatment efficacy. However, when the gel formulations were diluted with artificial urine, poloxamer gels lost their in situ gelling properties at body temperature, which is in conflict with the aimed formulation property. Therefore, 2% chitosan gel formulation was found to be a more promising carrier system for intravesical administration of nanoparticles.
Faculty of Pharmacy, Department of Pharmaceutical Technology, Ege University, Bornova, İzmir, Turkey.
Zeynep Ay
ZA
Şenyiğit
Faculty of Pharmacy, Department of Pharmaceutical Technology, Ege University, Bornova, İzmir, Turkey.
Sinem Yaprak
SY
Karavana
Faculty of Pharmacy, Department of Radiopharmacy, Ege University, Bornova, İzmir, Turkey.
Derya
D
İlem-Özdemir
Faculty of Pharmacy, Department of Radiopharmacy, Ege University, Bornova, İzmir, Turkey.
Çağrı
Ç
Çalışkan
ThioMatrix, Forschungs-Beratungs GmbH, Innsbruck, Austria.
Claudia
C
Waldner
Faculty of Medicine, Department of Pathology, Ege University, Bornova, İzmir, Turkey.
Sait
S
Şen
Institute of Pharmacy, Department of Pharmaceutical Technology, University of Innsbruck, Innsbruck, Austria.
Andreas
A
Bernkop-Schnürch
Faculty of Pharmacy, Department of Pharmaceutical Technology, Ege University, Bornova, İzmir, Turkey.
Esra
E
Baloğlu
D000283:Administration, Intravesical; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D015195:Drug Design; D005782:Gels / Q000737:chemistry; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D020442:Poloxamer / Q000737:chemistry; D013864:Thioglycolates / Q000737:chemistry; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D005782:Gels; D013864:Thioglycolates; D003841:Deoxycytidine; D020442:Poloxamer; C017487:2-mercaptoacetate; D048271:Chitosan; D000093542:Gemcitabine
chitosan; chitosan-TGA; gemcitabine HCl; intravesical administration; nanoparticle; poloxamer; superficial bladder cancer