pH Sensitive Hydrogels in Drug Delivery: Brief History

polymers Review pH Sensitive Hydrogels in Drug Delivery: Brief History, Properties, Swelling, and Release Mechanism, Material Selection and Applicatio...

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polymers Review

pH Sensitive Hydrogels in Drug Delivery: Brief History, Properties, Swelling, and Release Mechanism, Material Selection and Applications Muhammad Rizwan 1 , Rosiyah Yahya 1, *, Aziz Hassan 1 , Muhammad Yar 2 , Ahmad Danial Azzahari 1 , Vidhya Selvanathan 1 , Faridah Sonsudin 3 and Cheyma Naceur Abouloula 4 1

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Department of Chemistry, Universiti Malaya, 50603 Kuala Lumpur, Malaysia; [email protected] (M.R.); [email protected] (A.H.); [email protected] (A.D.A.); [email protected] (V.S.) Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, 54000 Lahore, Pakistan; [email protected] Centre for Foundation Studies in Science, Universiti Malaya, 50603 Kuala Lumpur, Malaysia; [email protected] Department of Physics, Faculty of Science Semlalia Marrakesh, Cadi Ayyad University, 40000 Marrakesh, Morocco; [email protected] Correspondence: [email protected]; Tel.: +60-3796-74258

Academic Editor: Wei Min Huang Received: 10 March 2017; Accepted: 6 April 2017; Published: 12 April 2017

Abstract: Improving the safety efficacy ratio of existing drugs is a current challenge to be addressed rather than the development of novel drugs which involve much expense and time. The efficacy of drugs is affected by a number of factors such as their low aqueous solubility, unequal absorption along the gastrointestinal (GI) tract, risk of degradation in the acidic milieu of the stomach, low permeation of the drugs in the upper GI tract, systematic side effects, etc. This review aims to enlighten readers on the role of pH sensitive hydrogels in drug delivery, their mechanism of action, swelling, and drug release as a function of pH change along the GI tract. The basis for the selection of materials, their structural features, physical and chemical properties, the presence of ionic pendant groups, and the influence of their pKa and pKb values on the ionization, consequent swelling, and targeted drug release are also highlighted. Keywords: pH sensitive hydrogels; swelling and drug release mechanism; biocompatible materials; drug delivery applications

1. Introduction 1.1. Brief History of Hydrogels The term hydrogel dates back to 1894 when this term was used by Lee et al. [1] for colloidal gels of certain inorganic salts. These gels are quite the opposite of the materials which are described by the term hydrogel today [2]. The first ever hydrogel reported in 1949 for biomedical implant was poly(vinyl alcohol) cross-linked with formaldehyde and marketed with the trade name Ivalon [3]. Later in 1958, Danno prepared poly(vinyl alcohol) hydrogels cross-linked by passing gamma irradiation through an aqueous solution [4]. The synthesis of poly(2-hydroxyethyl methacrylate) (pHEMA) gels for contact lens application by Wichterle and Lim [5] in 1960 was the revolution for present day hydrogels. pHEMA exhibited the characteristic properties of modern hydrogels like cross-linked networks that can show swelling upon absorption of excess of water without dissolution and can also retain their Polymers 2017, 9, 137; doi:10.3390/polym9040137