Abstract
Dual-drug-loaded lipid nanoparticle formulations (LNFs) namely solid lipid nanoparticles (SLNs) and nanostructured lipid carrier (are also solid lipid nanoparticles- a new generation of traditional SLNs) were developed and delivered to differentiated THP-1 cells. Developed LNFs have smooth and spherical surface morphology and nano range in size. In vitro drugs release profiles from these LNFs were slow and sustained. Particles were well co-localised in a different compartment (lysosome and endosome) of polarised macrophage by using suitable pH-dependent and antibody-mediated trafficking probe. Majority of the LNFs were also capable of existing in phago-lysosomal complex and able to effectively co-localise with the different cellular compartment of THP-1. The journey of the lipid carrier started through the formation of coated vesicle on differentiated macrophage surface, will further followed to idetify the efficient delivery of nano carrierat lysosomal and endosomal compartment in a sub cellular level of specific cell population. Comparative oral in vivo pharmacokinetic study revealed that nanostructured lipid carrier enhanced the pharmacokinetic profile compared to solid lipid nanoparticles and overall inclined the relative bioavailability by many folds. Cumulative results suggest that nanostructured lipid carrier could be an effective, alternative and promising lipid-mediated oral drug delivery approach than solid lipid nanoparticles.
Acknowledgements
Subham Banerjee is grateful to the Science and Engineering Research Board (SERB), Department of Science and Technology (DST), Government of India, for financial support to execute this research work through a young scientist award (Start-up research grant). The authors are thankful for the necessary TEM imaging facilities at International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India. The authors gratefully acknowledge the services given by the TheraIndx Lifesciences Pvt Ltd., Bangalore, India, for animal PK and biodistribution study. The gift of the THP-1 cell-line and access to the standard protocol for differentiation from Dr Ramandeep Singh, Associate Professor, Vaccine & Infectious Disease Research Centre (VIDRC), THSTI, Faridabad, India, is highly appreciated. Finally, the authors sincerely thank Dr. Pallavi Kshetrapal, Assistant Professor, THSTI for her valuable advice and assistance with the cell-line study. Subhadeep Roy is also thankful to the Indian Institute of Technology (IIT), New Delhi, India for providing access to necessary literature resources and essential digital library facilities for writing this manuscript.
Disclosure statement
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.