RT Journal Article
T1 Cyclodextrin–Amphiphilic Copolymer Supramolecular Assemblies for the Ocular Delivery of Natamycin
A1 Lorenzo Veiga, Blanca
A1 Sigurdsson, Hakon Hrafn
A1 Loftsson, Thorsteinn
A1 Álvarez Lorenzo, Carmen
K1 Block copolymers
K1 Cyclodextrins
K1 Ocular drug delivery
K1 Fungal keratitis
K1 Natamycin
K1 Mixed micelles
K1 Polyrotaxane
K1 Polypseudorotaxane
K1 Solubility
K1 HET-CAM assay
K1 Ocular permeability
AB Natamycin is the only drug approved for fungal keratitis treatment, but its low water solubility and low ocular penetration limit its efficacy. The purpose of this study was to overcome these limitations by encapsulating the drug in single or mixed micelles and poly(pseudo)rotaxanes. Soluplus and Pluronic P103 dispersions were prepared in 0.9% NaCl and pH 6.4 buffer, with or without α-cyclodextrin (αCD; 10% w/v), and characterized through particle size, zeta potential, solubilization efficiency, rheological properties, ocular tolerance, in vitro drug diffusion, and ex vivo permeation studies. Soluplus micelles (90–103 nm) and mixed micelles (150–110 nm) were larger than Pluronic P103 ones (16–20 nm), but all showed zeta potentials close to zero. Soluplus, Pluronic P103, and their mixed micelles increased natamycin solubility up to 6.00-fold, 3.27-fold, and 2.77-fold, respectively. Soluplus dispersions and poly(pseudo)rotaxanes exhibited in situ gelling capability, and they transformed into weak gels above 30 °C. All the formulations were non-irritant according to Hen’s Egg Test on the Chorioallantoic Membrane (HET-CAM) assay. Poly(pseudo)rotaxanes facilitated drug accumulation into the cornea and sclera, but led to lower natamycin permeability through the sclera than the corresponding micelles. Poly(pseudo)rotaxanes made from mixed micelles showed intermediate natamycin diffusion coefficients and permeability values between those of Pluronic P103-based and Soluplus-based poly(pseudo)rotaxanes. Therefore, the preparation of mixed micelles may be a useful tool to regulate drug release and enhance ocular permeability
PB MDPI
YR 2019
FD 2019
LK http://hdl.handle.net/10347/21337
UL http://hdl.handle.net/10347/21337
LA eng
NO Lorenzo-Veiga, B.; Sigurdsson, H.H.; Loftsson, T.; Alvarez-Lorenzo, C. Cyclodextrin–Amphiphilic Copolymer Supramolecular Assemblies for the Ocular Delivery of Natamycin. Nanomaterials 2019, 9, 745
NO This research was funded by MINECO [SAF2017-83118-R], Agencia Estatal de Investigación (AEI) Spain, Xunta de Galicia (Grupo de Referencia Competitiva ED431C 2016/008; Agrupación Estratégica en Materiales-AEMAT ED431E 2018/08), and FEDER (Spain). B.L.-V. acknowledges an Erasmus+ traineeship (IS-SM2018-81075)
DS Minerva
RD 24 abr 2026