Chitosan/β-glycerophosphate in situ gelling mucoadhesive systems for intravesical delivery of mitomycin-C

Oluwadamilola M Kolawole,Wing Man Lau,Vitaliy V Khutoryanskiy

doi:10.1016/j.ijpx.2019.100007

Oluwadamilola M Kolawole, Wing Man Lau + Show 1 more

Open Access

https://doi.org/10.1016/j.ijpx.2019.100007

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Abstract

The development of mucoadhesive in situ gelling formulations for intravesical application may improve the therapeutic outcomes of bladder cancer patients. In this work, chitosan/β-glycerophosphate (CHIGP) thermosensitive formulations have been prepared using three different chitosan grades (62, 124 and 370 kDa). Their ability to form in situ gelling systems triggered by changes in temperature upon administration to urinary bladder were evaluated using vial inversion and rheological methods. Texture analysis was used to study their mucoadhesive properties as well as syringeability through the urethral catheter. The retention of CHIGP formulations, with fluorescein sodium as the model drug, was studied on porcine urinary bladder mucosa ex vivo using the flow-through technique and fluorescent microscopy. CHIGP formulations containing mitomycin-C were prepared and drug release was studied using in vitro dialysis method. It was established that the molecular weight of chitosan influenced the thermogelling, mucoadhesive and drug release behaviour of the in situ gelling delivery systems. Formulations prepared from chitosan with greatest molecular weight (370 kDa) were found to be the most promising for intravesical application due to their superior gelling properties and in vitro retention in the bladder.

Highlights

Bladder cancer has been identified as a major clinical issue with prevalence and mortality rate escalating globally (Torre et al, 2015) and there is an increasing number of research in this area to improve drug delivery (Hu et al, 2018; Kolawole et al, 2017)
We present the first report on the formulation of chitosan/β-glycerophosphate gels using three grades of chitosan for intravesical drug delivery, with chitosan molecular weight modulating gelation, mucoadhesive and drug release profile of the CHIGP formulations
The degrees of deacetylation were 82 ± 1%, 72 ± 2%, and 71 ± 2%, respectively, which are in good agreement with those used by previous researchers to formulate CHIGP in situ gelling systems (Supper et al, 2014; Zhou et al, 2015)

Summary

Introduction

Bladder cancer has been identified as a major clinical issue with prevalence and mortality rate escalating globally (Torre et al, 2015) and there is an increasing number of research in this area to improve drug delivery (Hu et al, 2018; Kolawole et al, 2017). The mucoadhesive dosage forms are commonly prepared using polymers that interact with glycoprotein components of mucin through non-covalent bonding like hydrogen bonds, chain entanglements and electrostatic interactions (Khutoryanskiy, 2011; Davidovich-Pinhas and Bianco-Peled, 2014; Khutoryanskiy, 2014). They are desirable for drug delivery to the bladder because they may be able to overcome some inherent limitations of intravesical administration such as substantial drug dilution and wash-out during urine formation and elimination

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