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Comb-shaped amphiphilic polymers are rapidly emerging as an alternative approach to amphiphilic block copolymers for hydrophobic drug solubilization. These polymers consist of a homopolymer or copolymer backbone to which hydrophobic and hydrophilic pendant groups can be grafted resulting in a comb-like architecture. The hydrophobic pendants may consist of homopolymers, copolymers and other low-molecular weight hydrophobic structures. In this review, we focus on hydrophobically modified preformed homopolymers. Comb-shaped amphiphilic polymers possess reduced critical aggregation concentration values compared with traditional surfactant micelles indicating increased stability with decreased disruption experienced on dilution. They have been fabricated with diverse architectures and multifunctional properties such as site-specific targeting and external stimuli-responsive nature. The application of comb-shaped amphiphilic polymers is expanding; here we report on the progress achieved so far in hydrophobic drug solubilization for both intravenous and oral delivery.

Purpose: To evaluate the in vitro and in vivo pancreatic anticancer activity of a nano-sized formulation based on novel polyallylamine grafted with 5% mole cholesteryl pendant groups (CH(5)-PAA)., Methods: Insoluble novel anticancer drug, Bisnaphthalimidopropyldiaaminooctane (BNIPDaoct), was loaded into CH(5)-PAA polymeric self-assemblies by probe sonication. Hydrodynamic diameters and polydispersity index measurements were determined by photon correlation spectroscopy. The in vitro cytotoxicity evaluation of the formulation was carried out by the sulforhodamine B dye assay with human pancreatic adenocarcinoma BxPC-3 cells, while for the in vivo study, Xenograff mice were used. In vitro apoptotic cell death from the drug formulation was confirmed by flow cytometric analysis., Results: The aqueous polymer-drug formulation had a mean hydrodynamic size of 183 nm. The drug aqueous solubility was increased from negligible concentration to 0.3 mg mL(-1). CH(5)-PAA polymer alone did not exhibit cytotoxicity, but the new polymer-drug formulation showed potent in vitro and in vivo anticancer activity. The mode of cell death in the in vitro study was confirmed to be apoptotic. The in vivo results revealed that the CH(5)-PAA alone did not have any anti-proliferative effect, but the CH(5)-PAA-drug formulation exhibited similar tumour reduction efficacy as the commercial drug, gemcitabine., Conclusions: The proposed formulation shows potential as pancreatic cancer therapeutics.

Fluorescent amphiphilic polymers were produced by grafting different types and levels of hydrophobic pendant groups with intrinsic fluorescent properties (fluorenylmethoxy carbonyl (Fmoc), dimethylamino-1-naphthalenesulfonyl (Dansyl), and naphthalene (Naphth) to a water soluble homopolymer backbone, polyallylamine (PAA). Non-fluorescent hydrophobic pendant group (cholesteryl moieties) were also grafted onto PAA. The polymers were characterized with elemental analysis, NMR and FTIR spectroscopy. All polymers formed self-assemblies by probe sonication in water with sizes ranging from 120 to 199 nm and TEM images showed the presence of spherical particles. The critical aggregation concentration (CAC) varied from 0.093 to 1.5 mg ml−1 depending on the type of hydrophobic pendant groups. The Cholesteryl and Dansyl polymers showed the presence of one CAC while the Fmoc and Naphth grafted polymers revealed the presence of two CACs. The first CAC observed was possibly due to intermolecular aggregation while the second CAC at the higher polymer concentration was the result of excimer formation revealed by their fluorescent spectra. We reasoned that Naphth and Fmoc aromatic pendant groups possess a flat stereochemistry, thus allowing π- π stacking at higher concentrations. The presence of the N-dimethylamino group in the Dansyl moiety gives rise to a 3D structure, thus hindering any stacking. The understanding of the supramolecular assemblies formed by these fluorescent amphiphilic polymers will aid in the engineering of advanced materials with superior functionality for biomedical applications. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The physicochemical compatibility between amphiphilic polymers and hydrophobic drugs has been recognized as an important issue for improving the drug solubilisation in polymeric micelle formulations. In this work, poly-L-lysine (PLL) grafted by cholate pendants as the only hydrophobic moiety were synthesized in order to facilitate the solubilisation of sterol drugs. Results showed that micelles formed by cholate grafted PLL encapsulated significantly higher level of prednisolone and estradiol than palmitoylated PLL micelles, whereas the solubilisation capacity of non-sterol drug (griseofulvin) is inefficient for both polymers. This suggests that higher drug-polymer incorporation can be achieved by the inclusion of hydrophobic moieties with similar architecture as the drugs, i.e. 'drug-like' functional groups, which will be useful for the future design of colloidal systems for the encapsulation of specific drug. [ABSTRACT FROM AUTHOR]