Intracellular Delivery: An Overview

  • Dhanashree H. Surve
  • Prajakta Dandekar
  • Padma V. Devarajan
  • Anil B. JindalEmail author
Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 39)


Targeted intracellular delivery is gaining importance, especially for improved therapy of cancer and intracellular infections. Endocytosis or cellular internalization, a physiological process for intracellular delivery of nutrients or destruction of pathogens, involves two major pathways, namely phagocytosis or cell eating, which enable uptake of solid particles and pinocytosis or cell drinking. Pinocytosis includes fluid-phase endocytosis (macropinocytosis/micropinocytosis) and receptor-mediated endocytosis (RME). While phagocytosis, macropinocytosis, and micropinocytosis are nonselective, RME is a selective process of internalization, which is triggered by association of the receptor with specific ligands. Among endocytic processes, phagocytosis and RME are relied on for nanocarrier-based targeted drug delivery. This chapter describes various pathways with emphasis on phagocytosis and strategies to bypass lysosomal destruction of drugs. A major focus, however, is RME with a detailed discussion on clathrin, caveolin, and clathrin- and caveolin-independent pathways, and also provides a list of receptors based on the internalization pathway. Targeted delivery of drugs to subcellular organelles is also discussed. The discussion on the impact of nanocarrier properties on cellular internalization of nanocarriers throws light on factors to be addressed during nanoparticle design. This chapter thereby enables a comprehensive understanding of intracellular uptake in the context of targeted drug delivery.


Clathrin Caveolin Endosome Intracellular delivery Phagocytosis Pinocytosis Receptor-mediated endocytosis 



Activating protein 2


Bovine serum albumin


Clathrin assembly lymphoid myeloid leukemia protein


Cell adhesion molecule


Caveolae-mediated endocytosis


Cell division control protein 42 homolog


Circular dorsal ruffle


Clathrin-independent tubulovesicular carriers


Clathrin-mediated endocytosis


Cell-penetrating peptide


Cholera toxin


Dynamin 2




Diaphanous-related formins


Early endosome antigen 1


Endothelial growth factor


Enhanced permeation and retention


Epidermal growth factor receptor pathway substrate 15


Endosomal sorting complex required for transport


Folate-appended methyl-β cyclodextrin


Fer/cdc42 interacting protein 4 (CIP4) homology


Fc receptors


GTPase activating protein


Guanine nucleotide dissociation inhibitor


AP-enriched early endosomal compartments


Guanine nucleotide exchange factor


GTPase regulator associated with focal adhesion kinase 1


Hepatocyte growth factor


Human immunodeficiency virus


Human umbilical vascular endothelial cells




The Institute of Health Metrics and Evaluation


Immunoreceptor tyrosine-based activation


Lysosomal-associated membrane proteins


Low-density lipoprotein


Matrix metalloproteinase


1-Neutrophil cytosol factor 1/p47-phox


Neutrophil cytosol factor 2/p67-phox


Neutrophil cytosol factor 4/p40-phox


Nitric oxide radicals


Nitric oxide synthase 2


Natural resistance-associated macrophage protein 1


Platelet derived growth factor


Polyethylene glycol








Ras-related C3 toxin protein


Red blood cell


Reticuloendothelial system


Rab interacting lysosomal protein


Receptor-mediated endocytosis


Reactive oxygen species


Rho tyrosine kinase


Spontaneous membrane translocating peptide


Simian virus 40


Spleen-associated tyrosine kinase


Tumor growth factor


Triphosphonium ion


Vacuolar type H+-ATPase


Viral protein U


Vegetative storage protein


Wiskott-Aldrich syndrome protein


World Health Organization


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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Dhanashree H. Surve
    • 1
  • Prajakta Dandekar
    • 2
  • Padma V. Devarajan
    • 2
  • Anil B. Jindal
    • 1
    Email author
  1. 1.Department of PharmacyBirla Institute of Technology and Science, Pilani-campusPilani, JhunjhunuIndia
  2. 2.Department of Pharmaceutical SciencesInsitute of Chemical Technology, Deemed University, Elite Status and Centre of Excellence, Government of MaharashtraMumbaiIndia

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