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Intracellular Delivery: An Overview

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Targeted Intracellular Drug Delivery by Receptor Mediated Endocytosis

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 39))

Abstract

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.

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Abbreviations

AP2:

Activating protein 2

BSA:

Bovine serum albumin

CALM:

Clathrin assembly lymphoid myeloid leukemia protein

CAM:

Cell adhesion molecule

CavME:

Caveolae-mediated endocytosis

Cdc42:

Cell division control protein 42 homolog

CDR:

Circular dorsal ruffle

CLIC:

Clathrin-independent tubulovesicular carriers

CME:

Clathrin-mediated endocytosis

CPP:

Cell-penetrating peptide

CTX:

Cholera toxin

Dia2:

Dynamin 2

DOX:

Doxorubicin

DRF:

Diaphanous-related formins

EEA1:

Early endosome antigen 1

EGF:

Endothelial growth factor

EPR:

Enhanced permeation and retention

EPS15:

Epidermal growth factor receptor pathway substrate 15

ESCRT:

Endosomal sorting complex required for transport

FA-M-β-CD:

Folate-appended methyl-β cyclodextrin

FCH:

Fer/cdc42 interacting protein 4 (CIP4) homology

FcR:

Fc receptors

GAP:

GTPase activating protein

GDI:

Guanine nucleotide dissociation inhibitor

GEEC-GPI:

AP-enriched early endosomal compartments

GEF:

Guanine nucleotide exchange factor

GRAF1:

GTPase regulator associated with focal adhesion kinase 1

HGF:

Hepatocyte growth factor

HIV:

Human immunodeficiency virus

HUVEC:

Human umbilical vascular endothelial cells

Ig:

Immunoglobulin

IHME:

The Institute of Health Metrics and Evaluation

ITAM:

Immunoreceptor tyrosine-based activation

LAMP:

Lysosomal-associated membrane proteins

LDL:

Low-density lipoprotein

MMP:

Matrix metalloproteinase

NCF:

1-Neutrophil cytosol factor 1/p47-phox

NCF-2:

Neutrophil cytosol factor 2/p67-phox

NCF-4:

Neutrophil cytosol factor 4/p40-phox

NO−:

Nitric oxide radicals

NOS2:

Nitric oxide synthase 2

NRAMP-1:

Natural resistance-associated macrophage protein 1

PDGF:

Platelet derived growth factor

PEG:

Polyethylene glycol

PIP2:

Phosphatidyinositol-3,4-bisphosphonate

PIP3:

Phosphatidylinositol-3,4,5-phosphate

PLGA:

Poly(lactic-co-glycolic)acid

Rac1:

Ras-related C3 toxin protein

RBC:

Red blood cell

RES:

Reticuloendothelial system

RILP:

Rab interacting lysosomal protein

RME:

Receptor-mediated endocytosis

ROS:

Reactive oxygen species

RTK:

Rho tyrosine kinase

SMTP:

Spontaneous membrane translocating peptide

SV40:

Simian virus 40

Syk:

Spleen-associated tyrosine kinase

TGF:

Tumor growth factor

TPP:

Triphosphonium ion

V-ATPase:

Vacuolar type H+-ATPase

Vpu:

Viral protein U

VSP:

Vegetative storage protein

WASP:

Wiskott-Aldrich syndrome protein

WHO:

World Health Organization

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Authors and Affiliations

  1. Department of Pharmacy, Birla Institute of Technology and Science, Pilani-campus, Pilani, Jhunjhunu, Rajasthan, India

    Dhanashree H. Surve & Anil B. Jindal

  2. Department of Pharmaceutical Sciences, Insitute of Chemical Technology, Deemed University, Elite Status and Centre of Excellence, Government of Maharashtra, Mumbai, India

    Prajakta Dandekar & Padma V. Devarajan

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  1. Dhanashree H. Surve
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  2. Prajakta Dandekar
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  3. Padma V. Devarajan
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  4. Anil B. Jindal
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Correspondence to Anil B. Jindal .

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  1. Department of Pharmaceutical Sciences, Insitute of Chemical Technology Deemed University, Elite Status and Centre of Excellence Government of Maharashtra, Mumbai, India

    Padma V. Devarajan

  2. Department of Pharmaceutical Sciences, Insitute of Chemical Technology Deemed University, Elite Status and Centre of Excellence Government of Maharashtra, Mumbai, India

    Prajakta Dandekar

  3. Piramal Enterprises Limited, Pharmaceutical R&D, Mumbai, India

    Anisha A. D'Souza

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Surve, D.H., Dandekar, P., Devarajan, P.V., Jindal, A.B. (2019). Intracellular Delivery: An Overview. In: Devarajan, P., Dandekar, P., D'Souza, A. (eds) Targeted Intracellular Drug Delivery by Receptor Mediated Endocytosis. AAPS Advances in the Pharmaceutical Sciences Series, vol 39. Springer, Cham. https://doi.org/10.1007/978-3-030-29168-6_1

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