Abstract
One of the most serious issues faced by the healthcare sector is the development of multidrug resistance among various pathogens. It is such that developing new and more capable drugs takes far too long to counter such resistance. In order to overcome these concerns, this study focused on improving upon the coaxial electrospraying process by producing cloxacillin loaded albumin polycaprolactone (PCL) with a ZnO coating for sustained and activity enhanced drug delivery. Albumin-grafted, polycaprolactone-coated, zinc oxide-loaded cloxacillin (APCL-CLOX-ZnO) nanoparticles with a diameter of 85-110 nm were obtained via a coaxial electrospray technique. The encapsulation efficiency of cloxacillin of ZnO-CLOX was found to be approximately 60%. The loading efficiencies of ZnO-CLOX and APCL-CLOX-ZnO were found to be 40% and 28% respectively. Albumin was employed in order to impart immune evasion properties to the formulation. Drug-loaded ZnO NPs were analyzed using SEM, TEM, FT-IR and TGA. This novel formulation was shown to possess sustained release characteristics owing to the PCL and albumin coatings, relative to uncoated counterparts. ZnO-CLOX and APCL-CLOX-ZnO exhibited 72% and 52% cloxacillin release within 24 h. APCL-CLOX-ZnO exhibited potent antimicrobial activity against S. epidermidis, B. cereus and P. aeruginosa and some activity against E. coli with inhibition zones 32 ± 1.4, 34 ± 0.3, 32 ± 0.6 and 11 ± 0.4 mm, respectively. Cytotoxicity studies against murine preosteoblast cells revealed that the albumin-PCL coating served to drastically reduce initial toxicity against healthy mammalian cells. In vitro lung deposition study showed 70% of APCL-CLOX-ZnO particles can reach up to the alveoli level. Therefore, this novel coaxial nanoformulation may serve as a promising drug delivery platform for the treatment of bacterial infections including respiratory tract complications.