Chapter 11

Nanotechnology and Nanoparticles

Shelley A. Durazo and Uday B. Kompella

Abstract  Developing effective therapeutics to treat disorders of the back of the eye is an extremely difficult task due to the inability to deliver therapeutically relevant drug levels to the back of the eye using traditional methods (topical and systemic modes of administration). Innovative techniques and approaches are required to overcome the limitations associated with developing effective therapeutics to treat disorders of the back of the eye. Nanotechnology is a field that advances materials with a nano-dimension and provides several means for innovative design of nanosize drug delivery systems (nanosystems) to overcome biological barriers. Nanosystems based on polymers, lipids, proteins, and carbohydrates hold significant promise in enhancing drug delivery and hence, efficacy of small as well as large molecules intended for treating disorders of the back of the eye.

11.1  Introduction

Nanotechnology, the design and fabrication of diverse materials at the nano-scale (one-billionth of a meter), is exceptionally promising in almost every field including energy (Kamat 2007), electronics (Hughes 2000), information systems (Waser and Aono 2007), buildings (Paradise and Goswami 2007), vehicles (Llyod and Lave 2003), aerospace (Njuguna and Pielichowski 2003), as well as all areas of health sciences with the development of improved surgical tools (Satava 2002), nano-foods

U.B. Kompella (*) 

Nanomedicine and Drug Delivery Laboratory, Department of Pharmaceutical Sciences, University of Colorado, 12850 East Montview Blvd., C238-V20, Aurora, CO 80045, USA

Department of Ophthalmology, University of Colorado, Aurora, CO, USA e-mail: uday.kompella@ucdenver.edu

U.B. Kompella and H.F. Edelhauser (eds.), Drug Product Development for the Back of the Eye, 261 AAPS Advances in the Pharmaceutical Sciences Series 2, DOI 10.1007/978-1-4419-9920-7_11,

© American Association of Pharmaceutical Scientists, 2011

(Graveland-Bikker and de Kruif 2006), nanoparticle sunscreens (Wissing and Muller 2002), and drug delivery systems, the topic of this chapter. Drug delivery systems range from nanostructures to particles in the sub-visible range (microparticles) to visible implantable devices. The purpose of this chapter is to describe the materials, methods, and challenges in designing nanoparticulate delivery systems. Toward the end of this chapter, alternative delivery systems including microparticles and implants are also discussed.

As early as 1974, Dr. V.F. Smolen discussed methods to design, develop, and evaluate drug delivery systems to enhance drug efficacy in terms of bioavailability and drug response (Smolen et al. 1974). More than three decades later, innovative drug delivery systems are being marketed by several pharmaceutical companies including Allergan, Inc. (OzurdexTM), Bausch & Lomb, Inc. (Retisert®), and Abraxis BioScience, Inc. (Abraxane®). However, engineering drug delivery systems is a continuous process, given the challenges of new diseases and therapeutic agents. For this reason, several industrial agencies and academic institutions are continuously engaged in designing novel drug delivery systems. Dr. Ellis Meng and group at the University of Southern California (USC) has conducted pioneer research in developing novel implantable and refillable microelectromechanical system (MEMS)-based engineered ocular drug delivery systems (Li et al. 2008; Saati et al. 2009). This system accurately administers a finite amount of drug at certain time intervals and is also capable of easily being refilled by injection into the device. In fact, Dr. Meng is working with several collaborators including Replenish, Inc., California Retina Consultants and Doheny Eye Institute to develop a novel implantable, refillable pump for intraocular drug delivery into the vitreous by attaching the device externally to the vitreous. Novel drug delivery systems will continue to push the insights and forefront of pharmaceutical biotechnology and is the key to enhanced ocular therapeutics in terms of safety and efficacy.

This chapter will primarily focus on nanomaterials and systems that are biodegradable or bioresorbable, which will be collectively referred to as nanosystems. Various materials and methods are available to fabricate nanosystems of varying size, morphology, and composition (see Fig. 11.1). Size can range from just a few nanometers to thousands of nanometers and the morphology can range from spheres to highly ordered structures (e.g., rods, disks, cubes, and diamonds). In addition, the nanosystems can be solid (e.g., nanoparticles or nanospheres), fluid filled (e.g., nanoliposomes), gel-like (e.g., hydrogels), or soluble (e.g., water soluble drug-polymer conjugates). Common materials used to fabricate nanoparticles include both metallic and organic compounds. Examples of metallic nanosystems include gold, silver, and iron oxide nanoparticles for drug delivery. In the design of pharmaceutically viable drug carriers at doses suitable for long-term therapies, organic materials including polymers, lipids, proteins and carbohydrates are likely to be safer compared to metallic nanosystems. However, along with a drug molecule, the clinical viability of all delivery systems is ultimately determined by the risk:benefit analysis in a target patient population.