Topical ocular delivery of vancomycin loaded cationic lipid nanocarriers as a promising and non-invasive alternative approach to intravitreal injection for enhanced bacterial endophthalmitis management

Vancomycin (VCM) is a drug of choice for treating infections caused by Staphylococcus species, reported being the most causative agent of bacterial endophthalmitis. However, the ocular bioavailability of topically applied VCM is low due to its high molecular weight and hydrophilicity. The current study sought to explore whether the nanostructured lipid carriers (NLCs) fabricated via cold homogenization technique could improve ocular penetration and prolong the ophthalmic residence of VCM. A 2³ full factorial design was adopted to evaluate the influence of different process and formulation variables on VCM-loaded NLC formulae.

Highlights

NLC formula highly entrapped vancomycin (VCM) as a hydrophilic drug and represented considerable storage stability.

VCM-loaded NLC showed negligible toxicity profiles and safe for ophthalmic administration at RBC hemolytic assay.

NLC nanoparticles with remarkable ocular bioadhesion could highly penetrate corneal surfaces.

VCM-loaded NLC showed a ∼3-fold increase in the intravitreal concentration of VCM than drug suspension.

Topical ocular administration of VCM-loaded NLC had comparable outcomes to intravitreal injection of VCM in the management of severe bacterial endophthalmitis.

The optimized formula with the particle size of 96.4 ± 0.71 nm and narrow size distribution showed spherical morphology obtained by AFM and represented sustained drug release up to 67% in 48 h fitted to the Korsmeyer-Peppas model with probably non-Fickian diffusion kinetic. FTIR studies visualized the drug-carrier interactions in great detail. High encapsulation of VCM (74.8 ± 4.3% w/w) in NLC has been established in DSC and PXRD analysis. The optimal positively charged (+ 29.7 ± 0.47 mV) colloidal dispersion was also stable for 12 weeks at both 4 °C and 25 °C. According to in vivo studies, incorporation of VCM in NLC resulted in a nearly 3-fold increase in the intravitreal concentration of VCM after eye-drop instillation over control groups.

Besides, microbiological evaluation admitted its therapeutic effect within five days is comparable to intravitreal injection of VCM. Further, the optimized formula was found to be nonirritant and safe for ophthalmic administration in RBC hemolytic assay. Also, fluorescent tracking of NLCs on rabbit’s cornea showed an increase in corneal penetration of nanoparticles. Thus, it is possible to infer that the evolved NLCs are promising drug delivery systems with superior attainments for enhanced Vancomycin ophthalmic delivery to the eye’s posterior segment and improved bacterial endophthalmitis management.

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Article information: Kamyar Jounaki, Behzad Sharif Makhmalzadeh, Mostafa Feghhi, Asghar Heidarian, Topical ocular delivery of vancomycin loaded cationic lipid nanocarriers as a promising and non-invasive alternative approach to intravitreal injection for enhanced bacterial endophthalmitis management, European Journal of Pharmaceutical Sciences, Volume 167, 2021. https://doi.org/10.1016/j.ejps.2021.105991.