Chitosan/poly (lactic acid)-coated piceatannol nanoparticles exert an in vitro apoptosis activity on liver, lung and breast cancer cell lines.

The aim of the study was to synthesize nanoparticles (NPs) with chitosan (CS), and poly (lactic acid) (PLA) as a carrier for the drug piceatannol (PIC). The synthesized nanoparticles form the composite of polymeric-drug nanoparticles (CS/PLA-PIC NPs) by dropping method. The preliminary and stability studies were determined for the polymers drug-loading capacity and encapsulation efficiencies. The in vitro drug release study showed that NPs provided a continuous release of the entrapped PIC. The NPs found to be a good scavenger for DPPH, SOD and NO radicals. MTT and LDH assays revealed higher cytotoxic efficacy of CS/PLA-PIC NPs in HepG2, A549 and MCF7 cells compared to CS-PLA NPs and PIC. Dual staining results showed the early/late-stages of apoptotic and necrotic cells. Furthermore, cells treated with CS/PLA-PIC NPs showed fragmenting DNA and also demonstrated for apoptotic cells percentage by flow cytometry. These results suggested that upon CS/PLA-PIC NPs exposure leads to decrease in cancer cell viability due to apoptosis.

Enhancement of antimicrobial activity by liposomal oleic acid-loaded antibiotics for the treatment of multidrug-resistant Pseudomonas aeruginosa.

In this study, we examined the efficacy of liposomal oleic acid-based antibiotic formulations on 32 strains of multidrug-resistant Pseudomonas aeruginosa (MDRPa). The average size of liposomes were 93.12 ± 2.3 nm holding a negative zeta potential at -57.3 ± 0.89. Liposomal antibiotic formulations were tested against 32 MDRPa strains isolated from burn wounds and urine samples, which exhibited an MIC of ≤8 µg/mL, whereas MIC of free antibiotics ranged from 32 to >1024 µg/mL. The results clearly indicate that the liposomes composed of naturally occurring oleic acid, could be used therapeutically either alone or in combination with antibiotics to effectively treat P. aeruginosa infections.

Novel pyochelin-based PEGylated liposomes for enhanced delivery of antibiotics against resistant clinical isolates of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a problematic human pathogen resistant to almost all available antibiotics. The important prerequisite for these drugs to target this bacterium is an efficient delivery system. Siderophore-mediated drug delivery system is a promising approach to carry out antibiotics to the cells. Pyochelin, a siderophore of P. aeruginosa, was successfully synthesized in a five-step procedure. PEGylated liposomal pyochelin-antibiotic (L-Pch-Ab) carrier was fabricated by thin-film hydration method. L-Pch-Ab had an average size of 90.31 ± 0.11 nm holding a negative zeta potential at -54.12 ± 0.03 mV (PDI <2). The MIC determined by broth dilution method against three clinical strains isolated from burn wounds showed that L-Pch-Ab significantly reduced (≤16 µg/ml) the MIC values than those of free antibiotics. In the time kill assay, L-Pch-Ab was bactericidal against all strains at most time intervals at 2 × and 4 × MIC up to 24 h. TEM observations revealed that L-Pch-Ab was actively taken up by P. aeruginosa and exhibited membrane deformation within 2 h. Developed L-Pch-Ab fused intimately with the outer membrane of MDRPa and exhibited effective antibacterial activity than free Ab. Furthermore, L-Pch-Ab kills MDRPa within infected HaCaT keratinocytes without any cytotoxic effects at 4× MIC concentrations after 72 h. Thus, the specific targeting of L-Pch-Ab with its higher efficacy to deliver drug by limiting the toxicity will be a novel approach to fight infections caused by P. aeruginosa.