Enhancing targeted antibiotic therapy via pH responsive solid lipid nanoparticles from an acid cleavable lipid.

An acid cleavable lipid (SA-3M) was synthesized and used to develop pH-responsive solid lipid nanoparticles (SLNs) to deliver vancomycin base (VM-FB) to acidic infection sites. The size, polydispersity index and zeta potential of VM-FB_SA-3M_SLNs were 132.9±9.1nm, 0.159±0.01 and -26±4.4mV respectively, with 57.80±1.1% encapsulation efficiency. VM-FB release was significantly faster at pH6.5 than pH7.4. In vitro antibacterial activity against methicillin-susceptible and resistant Staphylococcus aureus (MSSA and MRSA) revealed that SLNs had enhanced activity at pH6.5 than pH7.4. In vivo study showed that the amount of MRSA remaining in the skin of VM-FB_SA-3M_SLNs treated mice was approximately 22-fold lower than VM-FB treated mice. Histological investigations revealed that signs of inflammation in the skin treated with VM-FB_SA-3M_SLNs were minimal. In conclusion, this study confirmed that SA-3M can form pH-responsive SLNs capable of releasing antibiotic specifically at acidic infection sites.

Polyelectrolyte complex of vancomycin as a nanoantibiotic: Preparation, in vitro and in silico studies.

Delivery of antibiotics by various nanosized carriers is proving to be a promising strategy to combat limitations associated with conventional dosage forms and the ever-increasing drug resistance problem. This method entails improving the pharmacokinetic parameters for accumulation at the target infection site and reducing their adverse effects. It has been proposed that antibiotic nanoparticles themselves are more effective delivery system than encapsulating the antibiotic in a nanosystem. In this study, we report on nanoparticles of vancomycin (VCM) by self-assembled amphiphilic-polyelectrolyte complexation between VCM hydrochloride and polyacrylic acid sodium (PAA). The size, polydispersity index and zeta potential of the developed nanoplexes were 229.7 ± 47.76 nm, 0.442 ± 0.075, -30.4 ± 5.3 mV respectively, whereas complexation efficiency, drug loading and percentage yield were 75.22 ± 1.02%, 58.40 ± 1.03% and 60.60 ± 2.62% respectively. An in vitro cytotoxicity study on three mammalian cell lines using MTT assays confirmed the biosafety of the newly formulated nanoplexes. Morphological investigations using scanning electron microscope showed cube shaped hexagonal-like particles. In vitro drug release studies revealed that the drug was completely released from the nanoplexes within 12h. In silico studies revealed that the nano-aggregation was facilitated by means of self-association of VCM in the presence of the polymer. The supramolecular pattern of the drug self-association was found to be similar to that of the VCM dimer observed in the crystal structure of the VCM available in Protein Data Bank. In vitro antibacterial activity against susceptible and resistant Staphylococcus aureus proved that the potency of VCM was retained after being formulated as the nanoplex. In conclusion, VCM nanoplexes could be a promising nanodrug delivery system to treat infections of S. aureus origin.