engleski

Impact of chitosan molecular weight and preparation method on nanoemulsion physico- chemical properties

Purpose Cationic nanoemulsions (NEs) are one of the formulation approaches to improve solubility of lipophilic ophthalmic drugs, eye-related bioavailability and drug residence at the ocular surface. The positive charge on the NE droplet surface enables interaction with negatively charged mucins at the ocular surface, which is the proposed mechanism of mucoadhesion 1. The aim of this study was preparation of optimized chitosan coated NE appropriate for dry eye disease treatment, employing lecithin (a natural lipid mixture of phospholipids commonly found in tears2) as a surfactant with overall negative charge that enables droplet interaction with positively charged chitosan chains. Materials and Methods For preparation of NEs the following substances were used: Miglyol 812 (Kemig, Croatia), lecithin S 45 (Lipoid, Germany), Kolliphor EL (BASF, Germany), chitosan (75 % DD ; LMw and MMw ; Sigma-Aldrich, Germany) and double- distilled water. NEs were produced using microfluidizer (Model M-110EH-30, Microfluidics, USA) and characterized in terms of droplet size, PDI and zeta potential (Zetasizer 3000 HS, Malvern Instruments, UK). In the first method, NEs without chitosan were produced first and were further coated with chitosan by its direct addition to the formulation and subsequent short magnetic stirring. In the second method, chitosan was added to the formulation prior processing on microfluidizer. Results NE without chitosan was successfully prepared (droplet size 181.1±2.9 nm ; PDI 0.092±0.026 ; zeta-potential -15.9±0.4 mV). When chitosan (0.05 – 0.5 % (w/w)) was added to the anionic NE the zeta-potential turned positive (29.2±.2 – 44.0±2.0) while the droplet size and PDI increased. The increase was more pronounced when MMw chitosan was used. Therefore, LMw chitosan was used for further studies. When NEs with 0.05 and 0.3 % (w/w) LMw chitosan were produced with the second method the obtained droplet sizes and PDI values were even smaller (183.9±1.5 nm, 0.116±0.008 ; 203.1±8.4 nm, 0.339±0.0.052). Conclusions Chitosan coated NEs were successfully produced using microfluidizer. Smaller droplets and PDIs were obtained when LMw chitosan was used. Chitosan Mw did not seem to have an influence on NE zeta-potential. The moment of chitosan addition was shown to have a major influence on NE droplet size and PDI. References 1. Gan, L. et al. Recent advances in topical ophthalmic drug delivery with lipid- based nanocarriers. Drug Discov. Today 18, 290– 297 (2013). 2. Willcox, M. D. P. et al. TFOS DEWS II Tear Film Report. Ocular Surface (2017). doi:10.1016/j.jtos.2017.03.006

cationic nanoemulsion ; chitosan ; lecithin

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