Gellan gum and its methacrylated derivatives as in situ gelling mucoadhesive formulations of pilocarpine: In vitro and in vivo studies

Laura E Agibayeva; Daulet B Kaldybekov; Natalia N Porfiryeva; Venera R Garipova; Rauash A Mangazbayeva; Rouslan I Moustafine; Irina I Semina; Grigoriy A Mun; Sarkyt E Kudaibergenov; Vitaliy V Khutoryanskiy

doi:10.1016/j.ijpharm.2020.119093

Gellan gum and its methacrylated derivatives as in situ gelling mucoadhesive formulations of pilocarpine: In vitro and in vivo studies

Int J Pharm. 2020 Mar 15:577:119093. doi: 10.1016/j.ijpharm.2020.119093. Epub 2020 Jan 28.

Affiliations

¹ Reading School of Pharmacy, University of Reading, Whiteknights, RG6 6AD Reading, United Kingdom; Department of Chemistry and Chemical Technology, Al-Farabi Kazakh National University, 050040 Almaty, Kazakhstan.
² Institute of Pharmacy, Kazan State Medical University, 16 Fatykh Amirkhan Street, 420126 Kazan, Russian Federation.
³ Department of Chemistry and Chemical Technology, Al-Farabi Kazakh National University, 050040 Almaty, Kazakhstan.
⁴ Institute of Pharmacy, Kazan State Medical University, 16 Fatykh Amirkhan Street, 420126 Kazan, Russian Federation; Central Research Laboratory, Kazan State Medical University, 6/30 Tolstogo Street, 420012 Kazan, Russian Federation.
⁵ Central Research Laboratory, Kazan State Medical University, 6/30 Tolstogo Street, 420012 Kazan, Russian Federation.
⁶ Institute of Polymer Materials and Technology, 050013 Almaty, Kazakhstan.
⁷ Reading School of Pharmacy, University of Reading, Whiteknights, RG6 6AD Reading, United Kingdom; Institute of Pharmacy, Kazan State Medical University, 16 Fatykh Amirkhan Street, 420126 Kazan, Russian Federation. Electronic address: v.khutoryanskiy@reading.ac.uk.

PMID: 32004682
DOI: 10.1016/j.ijpharm.2020.119093

Abstract

Gellan gum was chemically modified by the reaction with methacrylic anhydride to produce derivatives with 6, 14 and 49% methacrylation. The structure and substitution degrees of these derivatives were confirmed by ¹H NMR- and FTIR-spectroscopy. These derivatives are more hydrophobic compared to pristine gellan and form turbid solutions in water. In vitro study performed with formulations of sodium fluorescein containing gellan gum and its methacrylated derivatives indicated that methacrylation enhances their retention on bovine conjunctival mucosa. In vivo experiments with the formulations of pilocarpine hydrochloride containing gellan gum and methacrylated derivatives have demonstrated that all polymers enhance the drug effect significantly, but best performance is observed for the polysaccharide with 6% methacrylation.

Keywords: Gellan gum; Glaucoma; In situ gelling; Methacrylation; Mucoadhesion; Ocular drug delivery; Pilocarpine; Wash out(50).

Publication types

Comparative Study

MeSH terms

Adhesiveness
Animals
Cattle
Chemistry, Pharmaceutical
Conjunctiva / metabolism*
Drug Carriers / chemistry
Female
Fluorescein / chemistry
Gels
Hydrophobic and Hydrophilic Interactions
Male
Methacrylates / chemistry
Methacrylates / metabolism
Miotics / administration & dosage*
Miotics / chemistry
Miotics / metabolism
Mucous Membrane / metabolism
Pilocarpine / administration & dosage*
Pilocarpine / chemistry
Polysaccharides, Bacterial / chemistry*
Rabbits

Substances

Drug Carriers
Gels
Methacrylates
Miotics
Polysaccharides, Bacterial
Pilocarpine
gellan gum
Fluorescein