Nanoparticle-based targeted drug delivery

Abstract

Nanotechnology could be defined as the technology that has allowed for the control, manipulation, study, and manufacture of structures and devices in the "nanometer" size range. These nano-sized objects, e.g., "nanoparticles", take on novel properties and functions that differ markedly from those seen from items made of identical materials. The small size, customized surface, improved solubility, and multi-functionality of nanoparticles will continue to open many doors and create new biomedical applications. Indeed, the novel properties of nanoparticles offer the ability to interact with complex cellular functions in new ways. This rapidly growing field requires cross-disciplinary research and provides opportunities to design and develop multifunctional devices that can target, diagnose, and treat devastating diseases such as cancer. This article presents an overview of nanotechnology for the biologist and discusses the attributes of our novel XPclad((c)) nanoparticle formulation that has shown efficacy in treating solid tumors, single dose vaccination, and oral delivery of therapeutic proteins.

Figure 1. XPclad^® nanoparticle formulation

The milling jar holds heat-absorbent zirconium oxide planetary milling balls, rotates about its own axis as well as in the opposite direction, around a common axis of the chamber wheel. This produces the rotation of planetary balls and enables the milling of particles from macroparticles containing materials such as starch, polyethylene glycol, Texas red, and/or drug. By controlling the centrifugal force, varying the revolutions/sec of Ω, jar velocity (ω), radius (R), the size as well as number of the zirconium planetary balls, duration and number of cycles, the size of the core can be controlled to generate 5-30 nm up to 10-60 μm particles. In this system, the combination of impact and frictional forces cause the planetary balls to mill the contents in the jar.

Figure 2. Overview of XPclad^® nanoparticle applications

(Panel A) XPclad^® nanoparticles produced by planetary ball milling contain the desired biologically active agent(s) in a biopolymer excipient such as alginate, cellulose, starch or collagen and biologically active agents with >99% loading efficiency. XPclad particles are coated with polymers and/or ligands for controlled, protected, and targeted delivery of their contents. (Panel B) XPclad^® particle size can be engineered to various size ranges. (Panel C) Mice receiving dendritic cell-binding peptide-coated XPclad^® nanoparticles containing Streptococcus pneumonia pneumococcal surface protein A (PspA) peptide plus TLR7/8 agonist as adjuvant caused a significant reduction in viable bacteria after challenge compared to similarly challenged naïve animals or control mice. (Panel D) XPclad^® nanoparticles selectively target prostate cancer (PC3) cells but do not kill normal prostate epithelial cells (RWPE-1). Similarly, PC3 tumor-bearing mice that received folic acid-coated XPclad^® nanoparticles containing cisplatin showed significant tumor regression compared to similar control mice. (Panel E) Passive immunity to anthrax toxins was effected by oral delivery of anti-protective antigen (PA) MAbs using XPclad^® nanoparticles to neutralize anthrax toxin after systemic, oral, or respiratory exposure.