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Temperature- and pH-Dependent Drug Release of Block Copolymers of Methacrylic Acid and Poly(Ethylene Glycol) Methyl Ether Methacrylates

Eduardo C. Atayde Jr.1, Reynaldo Carlos K. Montalbo2, and Susan D. Arco1,2*

1Synthetic Organic Chemistry Research Laboratory, Institute of Chemistry,
University of the Philippines, Diliman, Quezon City 1101 Philippines
2Natural Sciences Research Institute, University of the Philippines Diliman,
Quezon City 1101 Philippines

 

*Corresponding authors: This email address is being protected from spambots. You need JavaScript enabled to view it.; This email address is being protected from spambots. You need JavaScript enabled to view it.

 

ABSTRACT

The block copolymers, poly(methacrylic acid)-b-poly(di(ethylene glycol) methyl ether methacrylate) (Block-D) and poly(methacrylic acid)-b-poly(poly(ethylene glycol) methyl ether methacrylate) (Block-P) were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization towards the development of stimuli-responsive carriers of poorly water-soluble drugs. The structures of the copolymers and the confirmation of successful block copolymerization were studied using proton nuclear magnetic resonance (1H-NMR) spectroscopy. Data from gel permeation chromatography (GPC) then showed polydispersity indices (PDI) close to 1.0, characteristic of RAFT polymerization. Stimuli-response studies revealed Block-D was responsive at pH 5.15 and 26°C while Block-P was responsive at pH 5.15 and 72°C. The corresponding micelles had particle sizes of 92.95-201.4 nm, as determined by dynamic light scattering (DLS), with critical micelle concentration (CMC) at about 10-1 mg/mL, per fluorescence studies. Using ibuprofen as the model drug, the drug loading content reached 11.76%, at 66.65% efficiency. In vitro release profiles then demonstrated 18% drug release within 5 h at stomach-like conditions, and 65% release within 5 h at small intestine-like conditions. Ultimately, cell viability assays of the blank and loaded micelles confirmed that neither is cytotoxic. These results show the immense potential and capability of the synthesized material as a drug delivery system for poorly water-insoluble drugs.

 

INTRODUCTION

The oral administration of pharmaceuticals is considered the most preferred method of drug delivery. It is economical, convenient, and non-intrusive. However, several physiological factors such as gastrointestinal pH, digestive enzymes, mucus, transit time, and permeability of different sections of the gastrointestinal tract can affect the transport of the drug (Martinez & Amidon 2002). To this end, stimuli-responsive polymers have been an attractive material towards the development of efficient drug delivery systems (DDS). Polymers, in general, are widely regarded as ideal DDS due to their biocompatibility and bio-imitative characteristics (El-Say & El-Sawy 2017). Stimuli-responsive polymers are a class of polymers that are sensitive to stimuli such as pH, ionic strength, temperature, light intensity, and pressure and respond to these by undergoing reversible phase changes (Patel & Koyani 2014). . . . . . read more

 

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