Supramolecular assembly of rifampicin and PEGylated PAMAM dendrimer as a novel conjugate for tuberculosis

Introduction: The study aimed to develop and explore the efficiency of a surface-modified 4.0 G PAMAM dendrimer as a novel delivery system for the anti-tuberculosis (TB) drug, rifampicin. Methods: The 4.0 G PAMAM dendrimer having various concentrations of polyethylene glycol (PEG) 2 kDa content was synthesized using 4-nitrophenyl chloroformate as an activator, and characterized using Fourier-transform infrared (FTIR) and proton nuclear magnetic resonance (1H NMR) analysis. Thereafter, rifampicin was loaded into dendrimers via simple dissolution solvent evaporation method, and characterized using different analytical techniques. The polymer encapsulation efficiency (EE%) was determined directly using a validated HPLC method. In vitro drug release was studied at pH 7.4. The MTT technique was used to assess the cytotoxicity of the dendrimer formulations against raw 264.7 cell lines. Results: The percentage coverage of 4.0 G PAMAM dendrimer peripheral with PEG was achieved in a range of 38%-100%. The EE% of the native dendrimer was 7.5% (w/w), and for PEGylated dendrimers was >60% (w/w). The dynamic light scattering (DLS) verified the nanosize of dendrimer formulations, and the zeta potential was positive with values greater than 12 mV. Scanning electron microscopy (SEM) images of dendrimer confirmed the spherical or semi-spherical shape of the nanoparticles, and differential scanning calorimetry (DSC) data verified drug entrapment. The PEGylated dendrimers showed a slower release rate compared to the native/ unmodified formulation and free drug. The toxicity of dendrimer was significantly improved after dendrimer PEGylation, and negligible toxicity was detected for formulations with 100% functionalization. Conclusions: The developed PEGylated G4 PAMAM dendrimers are suggested as a suitable drug carrier with negligible cytotoxicity, high loading potential, and prolonged-release behaviour for rifampicin.

Automated summary

The study successfully developed PEGylated G4 PAMAM dendrimers as a suitable drug carrier for rifampicin, with negligible cytotoxicity, high loading potential, and prolonged-release behavior. PEGylated dendrimers exhibited a slower release rate compared to the native/unmodified formulation and free drug, with significantly improved toxicity after PEGylation, and negligible toxicity detected for formulations with 100% functionalization.