Are engineered nanoparticles a potential means of controlling release in drug delivery systems?

Drugs can be administered to the human body through several anatomic routes. For therapeutic purposes, choosing the most suitable administration route is of unquestionable importance. Therefore, researchers are suggesting new approaches for the development of drug delivery systems (DDS).

When administering drugs, several factors must be considered, including:

• the properties of the drug;
• the illness to be treated; and
• the desired therapeutic time.

One novel approach is through micro-DDS, which present various benefits for drug administration. Scientific innovation in this field, which is based on nanotechnology, aims to create personalised treatment for a range of prevalent diseases, including cancer and diabetes. In addition to developments in application, efforts have been made to control several elements considered essential for enhancing the performance of a treatment, such as the rate, period and targeting of the delivery.

Factors that have compelled the scientific community to develop more advanced approaches include:

• the off-target effects of traditional drug delivery methods, which may cause severe side effects or have a toxic effect on healthy tissues;
• the impossibility of controlling drug levels over a long period, as doses peak at administration times when alternated with sub-therapeutic drug levels; and
• the enhanced bioavailability, high-drug loading or systemic stability in DDS that are based on nanoscale devices.

The interest in nanomedicine for treatment and diagnosis is reflected by the increasing number of publications and patents issued over the past few years. Patent filing activity reveals that until 2005, few inventions were published in this field. The period between 2009 and 2013 seems to have been a transition phase, resulting in a substantial increase in patenting activity (nearly 280% on the number of filings before 2008). The transition phase was in turn followed by a period of prolific publications; 2017 marking a huge increase in patenting activity. From 2009 to 2012 the highest growth rate occurred in patent filings related to cancer-targeting nanoparticle technology. Most nanoparticle DDS relate to several types of cancer, with the following patented nanoparticle-based cancer therapeutics already in the market:

• Doxil® (Caelyx® in Europe);
• Myocet®;
• DaunoXome®;
• DepoCyt®;
• Abraxane®;
• Genexol-PM®; and
• Oncaspar®.

A number of nano-DDS can be prepared using different types of material, such as:

• polymers;
• lipids;
• ceramics; or
• metallic nanoparticles.

The published inventions suggest that particles prepared from either natural or synthetic polymers have been extensively examined in order to be applied as DDS. The most widely used natural polymers in drug delivery are those based on lactic and glycolic acids. However, an N-(2-hydroxypropyl)methacrylamide-doxorubicin copolymer formulation was the first to enter clinical trials; the first marketed natural polymer was Abraxane® based on an Albumin-bound paclitaxel natural polymer. In 2005 Abraxane® was approved by the Food and Drug Administration for the treatment of metastatic breast cancer and in 2012 approval was ceded for its use against non-small cell lung carcinoma.

Overall, the technical challenges faced by the scientific community during the evolution of nano-DDS include improving:

• the therapeutic index;
• the properties of drugs, including:
  • size;
  • stability;
  • distribution; and
  • solubility;
• accuracy in drug delivery at specific sites;
• materials;
• responses to external stimuli; and
• methods of drug preparation.

Universities, research institutes, start-ups and small and medium-sized enterprises (especially in the United States and China) are the main contributors for development in nano-DDS. The United States is leading the way with more than half of the total number of patents filed in this field, followed by South Korea, Japan and Germany. The published literature reveals that most inventions have been filed by universities, including:

• Fudan University;
• University Suzhou;
• East China Normal University;
• China Pharmaceutical University; and
• Chongqing University.

Conclusion

The success of such therapies depends on the development of new delivery vectors that are capable of delivering drugs and molecules, while minimising the adverse side effects on healthy tissue and organs. There is much more still to explore in materials other than polymers. In the near future, it is likely that the development of new effective DDS, resulting from the integration of different interdisciplinary sciences, will find other vital application areas, such as gene therapy and cancer treatment.