Lysine and citric acid based pegylated polymeric dendritic nano drug delivery carrier and their bioactivity evaluation.

Abstract

The main objective of this work is to synthesize multifunctional nanodendritic structural molecules that can effectively encapsulate hydrophilic as well as hydrophobic therapeutic agents. Four different types of fourth-generation lysine-citric acid based dendrimer have been synthesized in this work: PE-MC-Lys-CA-PEG, TMP-MC-Lys-CA-PEG, PE-MS-Lys-CA-PEG, and TMP-MS-Lys-CA-PEG. The antibacterial drug cefotaxime (CFTX) was further conjugated to these dendrimers. The dendrimer and drug-dendrimer conjugate structures were characterized with the help of FTIR,¹H-NMR, and ¹³C-NMR spectroscopy. Zeta sizer, AFM, and HR-TEM techniques were used to investigate the particle size, surface topography, and structural characteristics of drug-dendrimer conjugates. In vitro drug release was then investigated using dialysis method. Various kinetic drug release models were examined to evaluate the type of kinetic drug release mechanism of the formulations. Cytotoxicity study revealed that the dendrimers encapsulated with CFTX exhibited 2-3% toxicity against healthy epithelial cells, indicating their safe use. Plain dendrimers show 10-15% hemolytic toxicity against red blood cells (RBC), and the toxicity was reduced to 2-3% when CFTX was conjugated to the same dendrimers. The 3^rd and 4^th generation synthesized drug-dendrimer conjugates exhibit a significantly effective zone of inhibition (ZOI) against both Gram-positive and Gram-negative bacteria. For Gram-positive bacteria, the lower concentration of 0.1 mg/mL showed more than 98% inhibition of drug-dendrimer conjugate samples against B. subtilis and more than 50% inhibition against S. aureus using 0.2 mg/mL, respectively. Moreover, samples with concentrations of 0.5 and 1.0 mg/mL exhibited more than 50% inhibition against S. typhimurium and E. coli, respectively.