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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.


Drug-loaded polymeric micelles with various targeting functions. (A) Antibody-targeted micelles (B) ligand-targeted micelles (C) Micelles with cell-pentrating function.
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Figure 3: Drug-loaded polymeric micelles with various targeting functions. (A) Antibody-targeted micelles (B) ligand-targeted micelles (C) Micelles with cell-pentrating function.

Mentions: Tumor cells and/or tumor vasculature frequently show increased expression of certain molecules (antigens or receptors) which are generally not expressed, or present at low levels on the surface of normal cells and surrounding normal tissues (Park et al., 2008; Kamaly et al., 2012). Active targeting exploits this feature of cancer cells to allow selective accumulation of anti-cancer therapeutics in the tumor tissue, tumor cells or intracellular organelles of the cell (Nie et al., 2007). Polymeric micelles can be functionalized for active targeting by chemically modifying their surface with targeting ligands that show a strong specificity for antigens or receptors over-expressed on cancer cells (Torchilin, 2007; Park et al., 2008) (Figure 3). Usually, the targeting ligands can be attached to the water-exposed free termini of hydrophilic blocks (PEG) of the micelles, so that they extend above the PEG brush and avoid steric hindrance when binding to their target receptors (Torchilin, 2001, 2007). Actively targeted polymeric micelles decrease side-effects of drugs by allowing preferential accumulation in diseased cells and also facilitate cellular uptake by receptor-mediated endocytosis (Park et al., 2008; Danhier et al., 2010). Active targeting especially benefits intracellular delivery of macromolecules like DNA, siRNA and proteins. The anti-tumoral efficacy of actively targeted delivery vehicles derives from their enhanced cellular internalization rather than just an increased tumor accumulation (Kirpotin et al., 2006).


Multifunctional polymeric micelles for delivery of drugs and siRNA.

Jhaveri AM, Torchilin VP - Front Pharmacol (2014)

Drug-loaded polymeric micelles with various targeting functions. (A) Antibody-targeted micelles (B) ligand-targeted micelles (C) Micelles with cell-pentrating function.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Drug-loaded polymeric micelles with various targeting functions. (A) Antibody-targeted micelles (B) ligand-targeted micelles (C) Micelles with cell-pentrating function.
Mentions: Tumor cells and/or tumor vasculature frequently show increased expression of certain molecules (antigens or receptors) which are generally not expressed, or present at low levels on the surface of normal cells and surrounding normal tissues (Park et al., 2008; Kamaly et al., 2012). Active targeting exploits this feature of cancer cells to allow selective accumulation of anti-cancer therapeutics in the tumor tissue, tumor cells or intracellular organelles of the cell (Nie et al., 2007). Polymeric micelles can be functionalized for active targeting by chemically modifying their surface with targeting ligands that show a strong specificity for antigens or receptors over-expressed on cancer cells (Torchilin, 2007; Park et al., 2008) (Figure 3). Usually, the targeting ligands can be attached to the water-exposed free termini of hydrophilic blocks (PEG) of the micelles, so that they extend above the PEG brush and avoid steric hindrance when binding to their target receptors (Torchilin, 2001, 2007). Actively targeted polymeric micelles decrease side-effects of drugs by allowing preferential accumulation in diseased cells and also facilitate cellular uptake by receptor-mediated endocytosis (Park et al., 2008; Danhier et al., 2010). Active targeting especially benefits intracellular delivery of macromolecules like DNA, siRNA and proteins. The anti-tumoral efficacy of actively targeted delivery vehicles derives from their enhanced cellular internalization rather than just an increased tumor accumulation (Kirpotin et al., 2006).

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.