pH-Sensitive Unimolecular Polymeric Micelles:  Synthesis of a Novel Drug Carrier

Abstract

Novel amphiphilic star-shaped polymers showing pH-sensitivity were synthesized by atom transfer radical polymerization. These new polymers present a core-shell structure similar to polymeric micelles, but are inherently stable to dilution and are referred to as unimolecular polymeric micelles. A four-armed multifunctional initiator was used for the sequential polymerization of hydrophobic ethyl methacrylate and tert-butyl methacrylate and hydrophilic poly(ethylene glycol)methacrylate. Polymers of molecular weight ranging from 9000 to 20,000 were obtained. Results of dynamic light scattering showed micelle size ranging from 11 to 40 nm. Unimolecular micelles were also analyzed by static light scattering in aqueous environment. Star-shaped polymers which presented the highest molar ratio of hydrophobic monomers tended to form high molecular weight aggregates in water. Hydrolysis of the tert-butyl methacrylate units permitted the introduction of ionizable methacrylic acid functions. Size distributions were bimodal at both acidic and basic pH. Since, the polymers were designed as potential delivery systems for the oral administration of hydrophobic drugs, they were titrated to evaluate the degree of ionization as a function of pH. In the stomach, the carboxylic functions are expected to be fully protonated. However, in the intestine, the micelles will be more than 40% ionized. Fluorescence studies were conducted in order to evaluate the polarity of the micellar core. Results showed an increase in polarity with pH due to the ionization of the acid functions present along the polymer chains. The pH rise was associated with an increase in the in vitro release rate of progesterone, which was used as hydrophobic drug model.

Synthesis of a Novel Electroactive ABA Triblock Copolymer and its Spontaneous Self‐Assembly in Water

“…[15] Functionalization of polymeric micelles may be one way to realize the controllable drug release which can be switchable, for example, making the polymeric micelle sensitive to changes of pH, electronic sign and magnetic power. [16][17][18] In this study, we successfully obtained a novel, electroactive triblock copolymer of poly(ethylene glycol) (PEG) and aniline pentamer (AP) (PEG-block-AP-block-PEG (PAP)), which firstly induced the aniline oligomer into a water system and prepared stable and uniform, large micellar aggregates by directly adding the PAP copolymer into aqueous solution. The micelle characterization was investigated using dynamic light scattering (DLS), fieldemission scanning electron microscopy (ESEM) and atomic force microscopy (AFM).…”

Assembling hyperbranched polymerics

“…48 Amphiphilic branched copolymers with hydrophilic and hydrophobic segments have been the subject of numerous studies. 49,50 The amphiphilic nature of these copolymers containing dissimilar segments gives rise to special properties in selective solvents, at surfaces, as well as in the bulk. 51 From synthetic prospective, modified hyperbranched poly (phenylenes) can be utilized as macroinitiators for the synthesis of star polymers by anionic polymerization.…”

Recent advances in oral vaccine development

“…The physiology of the gastro-intestinal tract, which is reinforced with various defense and clearance mechanisms, contributes to the equilibrium between immunity and oral tolerance in the gut. Gastric antigen degradation can be circumvented by using pH-sensitive polymers, (e.g., methacrylic acid, 19 hydroxypropyl methylcellulose phthalate 20 ) that protect antigens at acidic pH and respond to the slightly basic pH in the intestine due to their intrinsic ionizable functional groups leading to swelling or dissolution of the vehicle and site-specific antigen release. In contrast, other types of pH-sensitive polymers such as polymersomes dissolve under acidic conditions, which are particularly suitable for targeting tumors and endolysomoses.…”