engleski

Mucoadhesive properties of chitosan-coated nanoemulsions for improved dry eye disease treatment

Dry eye disease (DED) is a multifactorial disease affecting a growing number of people worldwide. It is characterized by a loss of homeostasis of the tear film, hyperosmolar stress and subsequent inflammation at the ocular surface [1]. Oil-in- water (o/w) nanoemulsion (NE) technology is one of the most promising DED treatment approaches. NEs enable incorporation of low soluble drug molecules and simultaneous replenishment of compromised tear film. Cationic NEs can further prolong drug residence time at the application site, due to their interaction with negatively charged ocular surface [2]. The right choice of the cationic surfactant/polymer is essential to achieve optimal balance between formulation properties and formulation effect on the ocular surface. The aim of this research was preparation, physicochemical characterization and in vitro mucoadhesion study of cationic o/w NEs coated with two different types of chitosan. For preparation of NEs we used: Miglyol 812 (Fagron, Croatia), lecithin S 45 (Lipoid, Germany), Kolliphor EL (BASF, Germany), low molecular weight (LMW) chitosan (50-190 kDa, 75 % DD ; Sigma-Aldrich, Germany), oligosaccharide lactate (OLIGO) chitosan (4-6 kDa, >90% DD, Sigma- Aldrich) and double-distilled water (DDW). NEs were produced as previously described [3] using microfluidizer (Model LM20, Microfluidics, USA) and characterized in terms of droplet size, PDI and zeta-potential by dynamic light scattering (DLS) (Zetasizer Ultra, Malvern Instruments, UK). Mucoadhesive properties were determined after mixing with porcine gastric mucin type II (Sigma- Aldrich) dispersion (20 and 1 %, w/w) using MCR 102 rheometer (Anton Paar, Austria) and Zetasizer Ultra. Statistical analyses were performed on the data obtained from the study on mucoadhesion using One-way ANOVA (P < 0.05). Chitosan-coated NEs were successfully prepared and characterized with droplet size < 200 nm, PDI < 0.2 and highly positive zeta-potential. Chitosan-coated NE mucoadhesive behavior was proven with both in vitro methods used. However, in both experiments, mucoadhesive properties of NEs were greater when OLIGO chitosan was used. In DLS method a notably higher droplet size increase was observed for NC LMW formulation, but besides electrostatic adsorption of mucin, the increase could be caused by droplet flocculation or coalescence, since the zeta-potential turned close to 0, leaving the formulation electrostatically unstabilized. Chitosan OLIGO has stronger impact on NE mucoadhesive properties than LMW chitosan, which is highly beneficial for ophthalmic application. [1] J. P. Craig et al., TFOS DEWS II Definition and Classification Report, Ocul Surf, 15 (2017) 276–283. [2] M. Ruponen and A. Urtti, Undefined role of mucus as a barrier in ocular drug delivery, Eur J Pharm Biopharm, 96 (2015) 442–446. [3] B. Jurišić Dukovski et al., Functional ibuprofen-loaded cationic nanoemulsion: Development and optimization for dry eye disease treatment, Int J Pharm, 576 (2020).

chitosan, dry eye disease, mucoadhesive, nanoemulsion

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