Background
Bacterial infections and antibiotic resistance are becoming major health concerns globally. Nanosized drug carrier systems are innovative strategies to overcome the limitations with conventional dosage forms for improved delivery and efficacy of antibiotics and also to overcome resistance. The synthesis of novel materials for the design of nanoantibiotics with enhanced performance is therefore essential. Therefore, the aim of this study was to synthesize a novel multiarm polymer (G-1-PETIM-PEG-b-PCL) using G1-poly(propyl ether imine) dendrimer (G1-PETIM) and a copolymer of methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) to offer high loading capacity and sustained delivery of vancomycin against susceptible and resistant Staphylococcus aureus.
Methods
The hybrid G1-PETIM was synthesized following a literature procedure and coupled to PEG-b-PCL to obtain G-1-PETIM-PEG-b-PCL. (Fig. 1). The synthesized G-1-PETIM-PEG-b-PCL was characterized for its structure by FTIR, 1H and 13C NMR, and MTT assay for biosafety. Vancomycin loaded micelles were prepared from G-1-PETIM-PEG-b-PCL, and characterized for size, surface charge, morphology, aggregation behavior, drug loading, drug release, stability and in vitro efficacy against sensitive and resistant S. aureus.
Results
The novel polymer G-1-PETIM-PEG-b-PCLwas successfully synthesized and characterized with FT-IR, 1H and 13C NMR. MTT assays showed a high percentage of cell viability ranging from 77% to 85% at all concentrations against all cell lines MCF 7, A549 and Hep G2 cells (Fig. 2), which confirmed the nontoxic nature of the polymer. Ultra-small unimolecular spherical micelles with average size, surface charge and polydispersity index of 52.48±2.6 nm (Fig. 3), -7.3±1.3 mV, 0.103 ±0.047 respectively and drug entrapment efficiency of >60% were successfully prepared. Vancomycin was released in a sustained manner and showed 91% release of the drug after 72 hours. The long circulation of the particles was further confirmed by the bovine serum albumin test. The formulation was found to be stable for more than 3 months. In vitro antibacterial tests revealed that at the end of 24 h period vancomycin-loaded micelles had 8- and 16-fold greater activity against S. aureus and MRSA respectively compared to bare vancomycin with prolonged activity for 5 days (Table 1). These findings confirmed the potential of G-1-PETIM-PEG-b-PCL as a promising nanocarrier for efficient antibiotic delivery.
