An overview of clinical and commercial impact of drug delivery systems

Abstract

Drug delivery systems are widely researched and developed to improve the delivery of pharmaceutical compounds and molecules. The last few decades have seen a marked growth of the field fueled by increased number of researchers, research funding, venture capital and the number of start-ups. Collectively, the growth has led to novel systems that make use of micro/nano-particles, transdermal patches, inhalers, drug reservoir implants and antibody-drug conjugates. While the increased research activity is clearly an indication of proliferation of the field, clinical and commercial translation of early-stage research ideas is critically important for future growth and interest in the field. Here, we will highlight some of the examples of novel drug delivery systems that have undergone such translation. Specifically, we will discuss the developments, advantages, limitations and lessons learned from: (i) microparticle-based depot formulations, (ii) nanoparticle-based cancer drugs, (iii) transdermal systems, (iv) oral drug delivery systems, (v) pulmonary drug delivery, (vi) implants and (vii) antibody-drug conjugates. These systems have impacted treatment of many prevalent diseases including diabetes, cancer and cardiovascular diseases, among others. At the same time, these systems are integral and enabling components of products that collectively generate annual revenues exceeding US $100 billion. These examples provide strong evidence of the clinical and commercial impact of drug delivery systems.

Keywords: Clinical translation; Drug delivery; Historical; Lab to clinic; Perspective; Pharmaceutics.

Figure 1

Schematics and brief descriptions of the 7 highlighted DDS: (i) microparticle-based depot formulations, (ii) nanoparticle-based cancer drugs, (iii) transdermal systems (patches highlighted here), (iv) oral drug delivery systems (OROS® highlighted here), (v) pulmonary drug delivery systems (inhalers highlighted here), (vi) implants and (vii) antibody-drug conjugates. Microparticle-based depot systems comprise formulations of drugs, peptides, or proteins encapsulated in biodegradable polymeric particles. These systems allow for the sustained and controlled release of therapeutics over a long period of time, allowing for a reduced number of treatments. Nanoparticles are drug carriers that are capable of encapsulating and protecting drugs from rapid degradation in vivo, improving both targeting and circulation profiles via surface modification with application-specific ligands, and controlling the rate of drug release from the particle. Transdermal patches contain a backing layer that prevents drug leakage, a reservoir to store the drug, a rate controlling layer that controls drug release and an adhesive layer that attaches to the skin. Transdermal patches allow for a painless, patient-compliant interface to facilitate systemic administration of drugs. OROS® technology is an osmotically driven system that controls the rate of drug release via the design of the osmotic pump and the osmotic properties of the drug. OROS® allows for the controlled release of therapeutics, via the oral route, which decreases dosing frequencey and side effects. Inhalers are compact devices that are used to store drug formulations which can be delivered as inhalable aerosolized sprays. Inhalers permit rapid absorption of drugs through the lungs, control over drug delivery via fixed doses, and the convenience of self-administration. Implants are devices that either passively, through material properties, or actively, through various actuation methods, control drug release rates. Implants allow for long-term delivery of therapeutics, often reducing the number of invasive procedures required to maintain similar therapeutic effect. Antibody drug conjugates are chemical conjugates of monoclonal antibodies and cytotoxic agents. Antibodies allow targeted delivery of highly potent cytotoxic drugs, thereby reducing systemic toxicity.

Figure 2

Normalized pie chart for clinical trial search. Search on ClinicalTrials.gov that counted the hits for clinical trials that are active and currently ongoing (but not recruiting). Thus, the data present trials that are actually in process. Data has been normalized to the sum of the total hits (180) for the following search keywords: (i) ‘Depot’ (41), (ii) ‘Transdermal’ (38), (iii) ‘Inhaler’ (27), (iv) ‘Subcutaneous implant’ (7) and ‘Intravitreal implant’ (9) and ‘Birth control implant’ (10), (v) ‘Nanoparticle and cancer’ (25), (vi) ‘Antibody drug conjugates’ (19) and (vii) ‘OROS’ (4). (Search conducted in Feb. 2014)

Figure 3

The typical path that academic discoveries follow from initial ideation to a final commercialized product. The challenges at each step are highlighted.