Newsletter: October 2016

The most sought-after route for administering medicine is oral, due to its ease and convenience for patients. Oral medicines need to be sufficiently water soluble for them to be taken up from the intestine, however, the majority of newly-discovered pharmaceutical compounds are poorly soluble in water.

Low solubility leads to decreased bioavailability and incomplete release from formulation, resulting in less of the drug being effective. Low solubility also limits the possibilities when choosing suitable delivery technologies.

This solubility problem is one of the main causes of difficulties with delivering existing drugs, and represents an obstacle for formulation to scientists.  Hence, the discovery and implementation of innovative methods of drug formulation are regarded as high priorities for researchers.

Chitosan nanoparticles can be used as a carrier molecule for the delivery of some lipophilic drugs (in other words, those being soluble in fats, but having low solubility in water). Chitosan nanoparticles are now being modified, such as by combining with other polymers like alginate and cyclodextrins, for more sustained or controlled release and targeting. These systems have great use in controlled release and targeting of almost all classes of bioactive molecules.

The objective of my research work at the University of Johannesburg (UJ) was to encapsulate essential oils extracted from specific medicinal plants. Essential oils are well known as natural products with important medicinal properties, especially in the treatment of cancer related symptoms. Despite several decades of extensive research and development in pharmaceutical chemistry, the poor solubility of lipophilic compounds in aqueous media remains a major barrier to their absorption, bioavailability and clinical efficacy. In cosmetics, for example, poor aqueous solubility and instability of oily compounds causes problems in formulation and fragrance stability.

Researchers involved in the development of pharmaceuticals have understood that drug delivery is a fundamental part of drug development and a wide range of drug delivery systems (DDS) have been designed. These include liposomes, micelles, dendrimers, microspheres, nanofibres and nanotubes. Ideally, all these systems should improve the stability, absorption and therapeutic concentration of the drug within the target site, while reducing unwanted side effects. In the last two to three decades of medical research, the need for effective drug delivery has emerged as a major concern, especially for the treatment of diseases such as cardiovascular disorders, cancer, malaria and tuberculosis (TB), which primarily require systematically administered therapies.

In cancer therapy, currently available cancer therapeutic strategies suffer from severe limitations that frequently result in treatment failure. The underlying basis for such failure is multifactorial, including poor oral bioavailability, insufficient targeting of the therapeutic agents, low water solubility and, consequently, emerging side effects and the spread of cancer to other organs. Amongst these, poor aqueous solubility remains one of the most critical challenges. For any drug to be absorbed in the small intestine and transported to the site of infection, it must possess enough aqueous solubility and be stable enough to pass through the gastro intestintal tract without degrading.

Encapsulation of lipophilic compounds into aqueous-soluble nanoparticulate systems provides a solution to several problems by improving the aqueous solubility of key compounds and providing a controlled way to deliver and release drugs with their full potential. The use of biodegradable polymers (such as polysaccharides) as drug carriers has long been of interest in controlled-release technology because these polymers are easily metabolised in the body.

The general biocompatibility and biodegradable profiles of polymeric nanoparticles are even more attractive with formulations that require more chronic dosing (such as cancer, TB and HIV/AIDS therapy), to avoid toxic accumulation of these materials in the human body. Biodegradable polymeric nanoparticles with hydrophilic surfaces have been designed to have longer circulation periods in the blood. Alginate, chitosan and cyclodextrins are such biopolymers and have received much attention due to their favourable properties. Nanoparticle carriers made of these bio-adhesive hydrophilic polysaccharides have the potential to increase the solubility of drugs and prolong the residence time, and therefore increase the absorption of loaded drugs. All these merits make polysaccharides promising biomaterials in drug delivery.

In our work, two nanoparticulate systems were prepared using a combination of the biomaterials (alginate, chitosan and cyclodextrin) by employing different methods. The encapsulation of the oily compounds in the nanoparticles increased their solubility in aqueous media (e.g. water) compared to the free, non-encapsulated compounds. The oil compounds were also released in a slow and sustained manner from the nanoparticles when incubated in simulated intestinal fluids. Due to the reduced particle size and high solubility it was anticipated that this new formulation (essential oil in nanoparticles) would be efficiently absorbed in the small intestine following oral administration. The slow and sustained release of the oily compounds from the nanoparticles would allow for a sustained treatment effect over a long period of time, which would in turn reduce the frequency of administering the drug. The next phase will be human application through the oral route.