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Multifunctional polymeric micelles for delivery of drugs and siRNA.

Jhaveri AM, Torchilin VP - Front Pharmacol (2014)

Bottom Line: They have gained immense popularity owing to a host of favorable properties including their capacity to effectively solubilize a variety of poorly soluble pharmaceutical agents, biocompatibility, longevity, high stability in vitro and in vivo and the ability to accumulate in pathological areas with compromised vasculature.In spite of the tremendous potential of siRNA, its translation into clinics has been a significant challenge because of physiological barriers to its effective delivery and the lack of safe, effective and clinically suitable vehicles.To that end, we also discuss the potential and suitability of multifunctional polymeric micelles, including lipid-based micelles, as promising vehicles for both siRNA and drugs.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University Boston, MA, USA.

ABSTRACT
Polymeric micelles, self-assembling nano-constructs of amphiphilic copolymers with a core-shell structure have been used as versatile carriers for delivery of drugs as well as nucleic acids. They have gained immense popularity owing to a host of favorable properties including their capacity to effectively solubilize a variety of poorly soluble pharmaceutical agents, biocompatibility, longevity, high stability in vitro and in vivo and the ability to accumulate in pathological areas with compromised vasculature. Moreover, additional functions can be imparted to these micelles by engineering their surface with various ligands and cell-penetrating moieties to allow for specific targeting and intracellular accumulation, respectively, to load them with contrast agents to confer imaging capabilities, and incorporating stimuli-sensitive groups that allow drug release in response to small changes in the environment. Recently, there has been an increasing trend toward designing polymeric micelles which integrate a number of the above functions into a single carrier to give rise to "smart," multifunctional polymeric micelles. Such multifunctional micelles can be envisaged as key to improving the efficacy of current treatments which have seen a steady increase not only in hydrophobic small molecules, but also in biologics including therapeutic genes, antibodies and small interfering RNA (siRNA). The purpose of this review is to highlight recent advances in the development of multifunctional polymeric micelles specifically for delivery of drugs and siRNA. In spite of the tremendous potential of siRNA, its translation into clinics has been a significant challenge because of physiological barriers to its effective delivery and the lack of safe, effective and clinically suitable vehicles. To that end, we also discuss the potential and suitability of multifunctional polymeric micelles, including lipid-based micelles, as promising vehicles for both siRNA and drugs.

No MeSH data available.


Related in: MedlinePlus

Enhanced permeability and retention (EPR) effect and passive targeting. Nanocarriers can extravasate into the tumors through the gaps between endothelial cells and accumulate there due to poor lymphatic drainage.
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Figure 2: Enhanced permeability and retention (EPR) effect and passive targeting. Nanocarriers can extravasate into the tumors through the gaps between endothelial cells and accumulate there due to poor lymphatic drainage.

Mentions: Passive targeting of nanocarriers including polymeric micelles relies on the tumor microenvironment. Their accumulation proceeds mainly via the EPR effect (Maeda et al., 2000). Tumor vasculature grows aberrantly to meet the ever-increasing nutrient and oxygen demand of the growing tumor, which leaves the endothelial cells poorly aligned with large fenestrations between them (Jain, 1987; Folkman, 1995; Roberts and Palade, 1997; Hobbs et al., 1998). This architectural abnormality and the production of vascular permeability factors like nitric oxide, bradykinin, matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) make the tumor blood vessels highly permeable (Wu et al., 1998; Fang et al., 2011). The growing tumor cells also compress the lymph vessels, particularly in the central portion of the tumor, causing them to collapse, resulting in poor lymphatic drainage from tumors (Padera et al., 2004). Both these phenomena—the increased vascular permeability and the defective lymphatic drainage not only allow leakage of blood plasma components and nanoparticles (e.g., micelles) into tumor tissues, but also allow them to be retained there (Maeda et al., 2000; Iyer et al., 2006). This phenomenon is termed the EPR effect (Matsumura and Maeda, 1986) (Figure 2).


Multifunctional polymeric micelles for delivery of drugs and siRNA.

Jhaveri AM, Torchilin VP - Front Pharmacol (2014)

Enhanced permeability and retention (EPR) effect and passive targeting. Nanocarriers can extravasate into the tumors through the gaps between endothelial cells and accumulate there due to poor lymphatic drainage.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4007015&req=5

Figure 2: Enhanced permeability and retention (EPR) effect and passive targeting. Nanocarriers can extravasate into the tumors through the gaps between endothelial cells and accumulate there due to poor lymphatic drainage.
Mentions: Passive targeting of nanocarriers including polymeric micelles relies on the tumor microenvironment. Their accumulation proceeds mainly via the EPR effect (Maeda et al., 2000). Tumor vasculature grows aberrantly to meet the ever-increasing nutrient and oxygen demand of the growing tumor, which leaves the endothelial cells poorly aligned with large fenestrations between them (Jain, 1987; Folkman, 1995; Roberts and Palade, 1997; Hobbs et al., 1998). This architectural abnormality and the production of vascular permeability factors like nitric oxide, bradykinin, matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) make the tumor blood vessels highly permeable (Wu et al., 1998; Fang et al., 2011). The growing tumor cells also compress the lymph vessels, particularly in the central portion of the tumor, causing them to collapse, resulting in poor lymphatic drainage from tumors (Padera et al., 2004). Both these phenomena—the increased vascular permeability and the defective lymphatic drainage not only allow leakage of blood plasma components and nanoparticles (e.g., micelles) into tumor tissues, but also allow them to be retained there (Maeda et al., 2000; Iyer et al., 2006). This phenomenon is termed the EPR effect (Matsumura and Maeda, 1986) (Figure 2).

Bottom Line: They have gained immense popularity owing to a host of favorable properties including their capacity to effectively solubilize a variety of poorly soluble pharmaceutical agents, biocompatibility, longevity, high stability in vitro and in vivo and the ability to accumulate in pathological areas with compromised vasculature.In spite of the tremendous potential of siRNA, its translation into clinics has been a significant challenge because of physiological barriers to its effective delivery and the lack of safe, effective and clinically suitable vehicles.To that end, we also discuss the potential and suitability of multifunctional polymeric micelles, including lipid-based micelles, as promising vehicles for both siRNA and drugs.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University Boston, MA, USA.

ABSTRACT
Polymeric micelles, self-assembling nano-constructs of amphiphilic copolymers with a core-shell structure have been used as versatile carriers for delivery of drugs as well as nucleic acids. They have gained immense popularity owing to a host of favorable properties including their capacity to effectively solubilize a variety of poorly soluble pharmaceutical agents, biocompatibility, longevity, high stability in vitro and in vivo and the ability to accumulate in pathological areas with compromised vasculature. Moreover, additional functions can be imparted to these micelles by engineering their surface with various ligands and cell-penetrating moieties to allow for specific targeting and intracellular accumulation, respectively, to load them with contrast agents to confer imaging capabilities, and incorporating stimuli-sensitive groups that allow drug release in response to small changes in the environment. Recently, there has been an increasing trend toward designing polymeric micelles which integrate a number of the above functions into a single carrier to give rise to "smart," multifunctional polymeric micelles. Such multifunctional micelles can be envisaged as key to improving the efficacy of current treatments which have seen a steady increase not only in hydrophobic small molecules, but also in biologics including therapeutic genes, antibodies and small interfering RNA (siRNA). The purpose of this review is to highlight recent advances in the development of multifunctional polymeric micelles specifically for delivery of drugs and siRNA. In spite of the tremendous potential of siRNA, its translation into clinics has been a significant challenge because of physiological barriers to its effective delivery and the lack of safe, effective and clinically suitable vehicles. To that end, we also discuss the potential and suitability of multifunctional polymeric micelles, including lipid-based micelles, as promising vehicles for both siRNA and drugs.

No MeSH data available.


Related in: MedlinePlus