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Therapeutic Applications of Polymeric Materials

Kishore Cholkar1, Gayathri Acharya2, Hoang M. Trinh3, Gagandeep Singh4

1Ingenus Pharmaceuticals/RiconPharma LLC, Denville, NJ, United States; 2GlaxoSmithKline, Collegeville, PA,

United States; 3University of Missouri—Kansas City, Kansas City, MO, United States; 4College of Staten Island, Staten Island, NY, United States

Contents

  • 1. Introduction 1
  • 2. Polymers as Drug Delivery Systems 2
  • 2.1 Polymer—Drug Conjugates 5
  • 2.2 Polymers in Ocular Drug Delivery 6
  • 2.3 Polymers in Tissue Engineering 7
  • 3. Polymers in Imaging and Diagnosis 8
  • 4. Conclusion 15

References 15

INTRODUCTION

Polymers are one of the most important agents in pharmaceuticals. Polymers provide a wide range of applications in diverse biomedical fields such as, but not limited to, drug delivery, tissue engineering, implants, prostheses, ophthalmology, dental materials, and bone repair [1,2]. For better understanding, polymers may be broadly classified as biodegradable and nonbiodegradable. Biodegradable polymers represent a most important class due to their biocompatibility with biological fluids (blood/serum), tissues, and cells with mini- mal/no toxicity [3]. Moreover, such polymers degrade over time due to hydrolysis and therefore require no surgical procedure for their removal. Examples include polylactic acid (PLA), polyglycolic acid (PGA), polylactic glycolic acid (PLGA), and polycaprolac- tones (PCL). Nonbiodegradable polymers can achieve long-term near-zero-order drug release kinetics. Examples of such polymers include polyvinyl alcohol (PVA), ethylene vinyl acetate, and polysulfone capillary fiber. Although biocompatible, these polymers are not biodegradable polymers. On the other hand, various natural and synthetic polymers have applications in drug delivery, imaging, and diagnosis. Examples include polyesters, polyamides, poly(amino acids), polyorthoesters, polyurethanes, and polyacrylamides [4]. Among them, thermoplastic aliphatic polyesters like poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and especially their copolymer poly(lactic-co-glycolic acid) (PLGA) are of significant interest due to their biocompatibility, process ability, and biodegradability.

© 2017 Elsevier Inc. All rights reserved.

Emerging Nanotechnologies for Diagnostics, Drug Delivery, and Medical Devices

ISBN 978-0-323-42978-8, http://dx.doi.org/10.1016/B978-0-323-42978-8.00001-2

Other most common and extensively studied biodegradable polymers include poly(E- caprolactone) (PCL), chitosan, gelatin, and poly(alkyl cyanoacrylates).

Early studies by Duncan et al., reported the development of first polymer—drug conjugates with applications for biomedical field [2,5]. Since then, several polymer—drug conjugates have been developed and commercialized. Polymeric systems may offer advantages such as improved drug stability, reduced toxicity, and enhanced targetability. Moreover, these polymers have been introduced in medical practice [6]. Biocompatible, biodegradable polymers and copolymers have demonstrated therapeutic potential in three major areas: (1) diagnostic applications, (2) therapeutic delivery, and (3) theranostics [6].

Polymer-based diagnostic agents are employed in diagnostic techniques such as fluorescence, imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), and ultrasound diagnosis [6]. Moreover, polymeric systems have been intensively investigated as carrier systems for active pharmaceutical ingredient/s [2]. Polymeric systems may offer protection and improve the half-life for highly unstable drugs such as resolvins [7]. Moreover, half-lives for biologics such as DNA and RNA and protein stability may be enhanced. Moreover, it can provide protection against in vivo degradation and premature inactivation [2]. Several stimuli (pH and temperature)-responsive smart polymeric drug delivery vehicles have been designed to achieve targeted drug delivery. Such polymeric systems exhibit improved efficacy and aid in optimizing the dose. Current investigations are being focused on applications of polymers in therapeutics [2]. For example, polymer synthesis methods allow designing the polymer architecture, which in turn plays an important role in biological activity [8,9]. Various ligands can be conjugated to polymer backbone, which may result in targeting a specific receptor and transporter site.

A drug delivery system must release the drug at or into the target as well as maintain therapeutic drug levels for a desired duration [10] in blood stream, allowing for distribution to tissues by the enhanced permeability and retention (EPR) effect. Additionally, active targeting may be achieved by the polymer carrier, a polymer—drug conjugate, or the drug [10].

 
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