Improving on nature:The role of nanomedicine in the development of clinical natural drugs

It is astonishing to observe that in spite of the technical hitches encountered in natural product research, more than 50% of drug substances are natural products or inspired by natural compounds, covering a variety of therapeutic indications with a great range of chemical structures. Several latest reviews have tinted the tangible importance of natural products to the drug discovery process, being over a hundred natural product-derived compounds which are currently undergoing clinical trials [1]. Although these natural products represent a large source of potential drugs, mostly of them have limited clinical use due to chemical instability, low absorption and biodistribution, first pass metabolism, little accumulation in the organs of the body, inadequate efficacy or safety profiles [2,3]. These characteristics strongly influence the delivery of natural products using conventional dosage forms. Different strategies have been adopted to overcome these limitations, such as development of semisynthetic compounds or synthetic analogues, or the production of prodrugs but in mostly of the cases have not been satisfactory.

Nanotechnology has an enormous impact in medical technology, significantly improving the performance of drugs in terms of efficacy, safety and patient compliance.

Nanosized drug delivery systems have already entered in clinical use with the most pressing challenge the design of multifunctional, structured materials able to target specific tissues or organs or containing functionalities to allow transport across biological barriers. These delivery systems can be smartly designed to tag a variety of chemical, molecular and biological entities. Researchers mainly focused priority areas such as specific target diseases such as cancer, neurodegenerative and cardiovascular diseases. A successful drug carrier system needs to demonstrate optimal drug loading and release properties, long shelf-life exerting much higher therapeutic efficacy and lower side-effects as well [4].

Promising nanoparticles, nanocapsules, lipid nanoparticles, dendrimers, micelles and liposomes of taxol and derivatives, berberin, artemisinin, huperzine, camptothecin, polyphenols such as resveratrol, curcumin, sylibin and catechins have been reported in the literature for their considerable potential in the development of new dosage forms of natural drugs. So far, the results obtained from the nanoencapsulated natural products are very encouraging generally having a sustained release and improved bioavailability at much lower doses. We have entered the era of nanomedicine with natural drugs, it is probably the most salient feature of the field and a decisive step toward the demonstration that natural drugs can continue to play a key role in modern clinic.

References

[1] M.S. Butler. Natural products to drugs: natural product-derived compounds in clinical trials. Nat. Prod. Rep. 25: 475–516 (2008).

[2] M. Coimbra, B. Isacchi, L. van Bloois, J.S. Torano, A. Ket, X. Wu, F. Broere, J.M. Metselaar, C.J. Rijcken, G. Storm, A. R. Bilia, R.M. Schiffelers. Int. J. Pharm. 416: 433–442 (2011).

[3] B. Isacchi, M.C. Bergonzi, M. Grazioso, C. Righeschi, A. Pietretti, C. Severini, A.R. Bilia. Artemisinin and artemisinin plus curcumin liposomal formulations: Enhanced antimalarial efficacy against Plasmodium berghei-infected mice. Eur. J. Pharm. Biopharm. 80: 528–534 (2012).

[4] P. Couvreur, C. Vauthier. Nanotechnology: Intelligent design to treat complex disease. Pharm. Res. 23: 1417–1450 (2006).