Unipolymeric Micelles - American Chemical Society

Chapter 18

Downloaded by NORTH CAROLINA STATE UNIV on September 24, 2012 | http://pubs.acs.org Publication Date: November 28, 2000 | doi: 10.1021/bk-2001-0780.ch018

Unipolymeric Micelles Properties & Biological Significance 1,3

1,4

2

Jian Guo , Hongbo Liu , Stephanie Farrell , Leila NikkhouyAlbers , Kristi Schmalenberg and Kathryn E. Uhrich 1

1

1,*

1

Department of Chemistry, Rutgers University, Piscataway, NJ 08855 Department of Chemical Engineering, Rowan University, Glassboro,NJ08028 Current Address: Merck Laboratories, Rahway, NJ 07065 Current Address: Department of Surgery, Emory University, Atlanta, GA 30322 2

3

4

The most serious problem with formulating drugs in surfactant systems is the paucity of suitable, biodegradable materials available for drug delivery. The polymers discussed herein are directly dispersible in aqueous solution and able to water -solubilize hyrdophobic drugs. Using previously developed synthetic methods, systematic alterations in polymer structure are easily attainable. Control over the chain length, ratio of hydrophobic to hydrophilic components, and the polymer properties enables control of the size and hydrophobic characteristics of the polymer complexes in water. The nature and stability of the polymeric drug carrier are of fundamental importance in understanding their potential drug carrying capacity. Of particular interest is the physical nature of the polymer core; knowledge about the core facilitates drug solubilization and subsequent release.

298

© 2001 American Chemical Society

In Stimuli-Responsive Water Soluble and Amphiphilic Polymers; McCormick, C.; ACS Symposium Series; American Chemical Society: Washington, DC, 2000.

299


Introduction A methodology to synthesize degradable, hyperbranched, amphiphilic polymers with micellar properties was recently reported, (i) The polymers consist of mucic acid (a sugar), alkyl chains (fatty acid-like units) and poly(ethylene glycol) (PEG). The structures are highly branched with a hydrophobic core of alkyl chains surrounded by a hydrophilic surface layer of PEG. PEG is a nontoxic, synthetic polymer that is often adsorbed or chemically bound to surfaces of hydrophobic polymeric matrices to prolong device half-life in blood. (2, 3) Because the hydrophilic PEG creates a steric barrier to prevent interaction with proteins or cells (4), long-term blood circulation occurs due to the avoidance of renal filtration and reduction in uptake by the liver. (5) Our synthetic goal was to create materials with controllable, predictable characteristics such as water-solubility and ability to encapsulate (i.e., watersolubilize) hydrophobic drugs. We hypothesized that water-solubility and encapsulation ability would be determined by the ratio of lipophilic, alkyl chains located in the polymer 'interior' (or core) relative to the hydrophilic, ethylene glycol chains at the polymer 'exterior' (or shell). The hydrophilic/lipophilic ratio may also influence the rate of hydrolysis (i.e., biodégradation), whereas the choice of the polymer components affects the polymer toxicity or biocompatibility.

Polymer Synthesis The synthetic scheme is below. Mucic acid (MA) (1) was acetylated using acyl chlorides (i.e., propanoyl, hexanoyl and lauroyl chloride) to yield various mucic acid derivatives (2-4). The mucic acid derivatives (2-4) were coupled to l,l,l-tris(hydroxyphenyl) ethane (5) to afford various molecules 6-8 using dicyclohexylcarbodiimide (DCC) and dimethylaminopyridine (DMAP). Tris(hydroxyphenyl)ethane (5) was chosen because it is trifunctional, the aromatic groups provide a spectroscopic tag for compound identification, and the aromatic moieties can potentially enhance the encapsulation of aromatic drug molecules. Finally, the core molecules (6-8) were condensed with monomethoxy-terminated ethylene oxide chains of various lengths using DCC/DMAP to give the unimolecular micelle structures (9-13). After the final coupling reaction, excess PEG is removed by a combination of fractionation and chromatographic separation techniques. All products were purified by chromatography, except the final polymers (9-13) were purified by multiple, fractional precipitations into ethyl ether.

In Stimuli-Responsive Water Soluble and Amphiphilic Polymers; McCormick, C.; ACS Symposium Series; American Chemical Society: Washington, DC, 2000.

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H QH

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.OH

HO'

x

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3

3

w

Η φΗφτΓθ3

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x=1,4,10

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Unipolymeric Micelles - American Chemical Society

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