Mapping the potential of thiolated pluronic based nanomicelles for the safe and targeted delivery of vancomycin against staphylococcal blepharitis

Abstract

The present study was performed to develop mucoadhesive vancomycin loaded thiolated pluronic F68 polymeric nanomicelles against staphylococcal blepharitis. The polymeric micelles were intended to be mucoadhesive in nature with prolonged retention at site of infection to address the barriers in topical delivery to eyelids. The mucoadhesive and enhanced retention of polymeric micelles was investigated by synthesis of vancomycin loaded thiolated polymeric micelles of tri block copolymer Pluronic F68. The drug loaded thiolated polymeric micelles were characterized for their zeta potential, particle size, PDI, release profile, animal studies and stability. The FTIR analysis of the thiolated polymeric nanomicelles confirmed successful synthesis of vancomycin loaded thiolated polymeric nanomicelles (Vnc-PF68-Cys) with no interaction between vancomycin and polymer. X-Ray diffraction studies (XRD) showed crystalline nature of vancomycin in the thiolated polymeric nanomicelles. The surface roughness of the developed polymeric nanomicelles was evident from results of AFM (Atomic force microscopy) images. TEM (Tranmission electron microscopy) confirmed spherical shape and unilamelar nature of nanomicelles. Furthermore, Vnc-PF68-Cys nanomicelles were found to be stable regarding particle size, zeta potential and polydispersity index with nanosize, low polydispersity index and negative zeta potential. Thermal stability of the formulation was confirmed by DSC (Differential scanning calorimetry). Visual inspection of the nanoformulation showed particles-free clear solution. Mucoadhesive property was evaluated by rheological behaviour of formulation when mixed with freshly prepared mucin solution in terms of viscosity that showed 2 folds increase in viscosity upon thiolation of formulation due to thiols group in polymer backbone forming disulfide linkage with cysteine groups of mucins. Release profile showed sustained drug release up to 48 h for thiolated formulation with 98% drug released under sink conditions. The prepared thiolated nanomicelles were found non-toxic towards mice. Based on the results, the developed Vnc-PF68-cys polymeric nanomicelles formulation seems to be promising mucoadhesive formulation for ocular deliveryagainst staphylococcal blepharitis.