Critical issues in site-specific targeting of solid tumours: the carrier, the tumour barriers and the bioavailable drug
- 5 February 2008
- journal article
- review article
- Published by Informa UK Limited in Expert Opinion on Drug Delivery
- Vol. 5 (2), 205-219
- https://doi.org/10.1517/17425247.5.2.205
Abstract
Background: The concept of passive and active targeting of solid tumours with intravenously administered particulate and macromolecular carriers is an attractive one that has received considerable attention and promising results have emerged from such attempts at the clinical level. Particulate and polymeric drug carriers have the capability to deliver from 2- to 10-times more drug to solid tumours compared with the administered drug in its free form, and it is through the altered pharmacokinetics and pharmacodynamics of the encapsulated/conjugated drugs relative to free drugs that anticancer drug-induced toxicity is dramatically reduced. Objectives: It is the intention of this article to examine the role of selected particulate and macromolecular entities as carriers of anticancer drugs and their ability to target different components of solid tumours following the intravenous route of injection, and release their cargo in a bioavailable form at levels that exceed the minimum cytotoxic concentration. Methods: The authors of this paper have focused on carrier behaviour (pharmacokinetics of single and multiple injections, and new toxicity issues that may arise from different dosing schedules and dose intensities, as well as from the carrier itself), pathophysiological factors regulating particulate and macromolecular transport into tumours (structural arrangements of tumour vasculature, tumour vascular permeability, interstitial hypertension and interstitial transport), and biochemical and physicochemical factors controlling drug release from extravasated carriers (the bioavailable drug). Conclusion: Nanoscale drug carriers can passively target solid tumours, but achieving therapeutic responses involves pathophysiological processes that control carrier transport into tumours and biochemical factors regulating drug release from extravasated carriers and maintaining free drug levels above the minimum cytotoxic concentration. It is conceivable that future sophistication in tumour targeting and the outcome of end results will depend on an improved understanding of tumour biology and biological barriers, as well as advances in carrier design and nanoengineering.Keywords
This publication has 71 references indexed in Scilit:
- Pulsed-High Intensity Focused Ultrasound and Low Temperature–Sensitive Liposomes for Enhanced Targeted Drug Delivery and Antitumor EffectClinical Cancer Research, 2007
- VEGF-A and the Induction of Pathological AngiogenesisAnnual Review Of Pathology-Mechanisms Of Disease, 2007
- Biomimetic amplification of nanoparticle homing to tumorsProceedings of the National Academy of Sciences, 2007
- A Bacterial Protein Enhances the Release and Efficacy of Liposomal Cancer DrugsScience, 2006
- Polymer conjugates as anticancer nanomedicinesNature Reviews Cancer, 2006
- Low and high molecular weight poly(l‐lysine)s/poly(l‐lysine)–DNA complexes initiate mitochondrial‐mediated apoptosis differentlyFEBS Letters, 2005
- Block copolymer micelles as a solution for drug delivery problemsExpert Opinion on Therapeutic Patents, 2005
- Pharmacokinetics of doxorubicin administered i.v. as Myocet (TLC D-99; liposome-encapsulated doxorubicin citrate) compared with conventional doxorubicin when given in combination with cyclophosphamide in patients with metastatic breast cancerAnti-Cancer Drugs, 2003
- Pharmacokinetics of Pegylated Liposomal DoxorubicinClinical Pharmacokinetics, 2003
- Acquired and specific immunological mechanisms co-responsible for efficacy of polymer-bound drugsJournal of Controlled Release, 2002