Malaysia has set out to focus on cutting edge research areas that include nanotechnology. One particular field that has gained advantage due to the nanotechnology revolution is pharmacy. A new distinctive discipline has since evolved, namely nanopharmacy. Nanopharmacy involves the preparation and delivery of ultra small pharmaceuticals or therapeutic substances in the molecular and nanometer (nm) size range (preferably 1 to 100 nm) to the desired site of action in the human body, without affecting healthy organs and tissues. The importance of this science relies on the fact that almost 95% of the actual discovered drugs present poor pharmacokinetics and bioavailability properties.
The aim of nanopharmacy is to improve drug pharmacokinetics (what the body does to the drug), pharmacodynamics (what the drug does to the body), non-specific toxicity, immunogenicity and biorecognition of systems in order to attain maximum efficacy and minimum undesirable side effects. To achieve this aim, drug formulation, route of administration and specific targeting are the major parameters considered.
Progress in drug formulation has produced new nano-delivery systems or nanocarriers. They are useful as drug carriers for the effective transport of poorly soluble therapeutic substances. Nanocarriers, in the form of polymer, lipid, ceramic or protein, can be designed to control degradation, react to stimuli and be site-specific. When a drug is attached to a nanocarrier it can be delivered to the appropriate site, released in a controlled way and protected from undergoing premature degradation, especially in the hostile condition of the stomach. Researchers utilize polymers and lipid substances that have particular physical or chemical characteristics, such as biodegradability, biocompatibility and responsiveness to pH or temperature changes.
Route of Administration
Route of administration is as important as the drug itself to achieve the desired therapeutic effect. Nanocarriers are developed with the aim of crossing a particular physical barrier, such as the blood–brain barrier; or on finding alternative and acceptable routes for the delivery of a new generation of protein-based drugs. The peroral route is the most frequently used drug delivery route due to higher patient acceptability and convenience.
However, increasing number of new effective therapeutics are protein- and peptide-based chemicals that do not cross mucosal surfaces and biological membranes, and cannot withstand the degradative environment that exists in the gastrointestinal tract. Thus, the peroral route might be used in the future for administration of sensitive compounds if appropriate protection could be granted to the drugs by the nanosystems.
Transdermal drug delivery avoids problems such as gastrointestinal irritation, metabolism, variations in delivery rates and interference due to the presence of food. Limitations include slow penetration rates, lack of dosage flexibility and/or precision, and a restriction to relatively low dosage drugs.
Parenteral routes of drug delivery using, e.g. intravenous, intramuscular or subcutaneous administrations are very important, but more invasive compared to peroral and transdermal route of drug delivery. However nanoscaled drug carriers have the potential to improve the delivery of drugs through nasal and sublingual routes, both of which avoid first-pass metabolism (and consequently degradation) by the liver. In addition, there is the possibility of improving the ocular bioavailability of drugs if administered in a colloidal drug carrier.
Another important route of drug delivery is through the lungs. Pulmonary delivery using metered dose inhaler systems may contain nanostructures such as liposomes, micelles, nanoparticles and dendrimers. It offers local targeting for the treatment of respiratory diseases and increasingly appears to be a viable option for the delivery of drugs systemically. However, the success of pulmonary delivery of protein drugs is diminished by proteases and macrophages in the lung, which reduce their overall bioavailability, and by the barrier between the blood capillary and alveolar air.
Targeting can be either passive or active. An example of passive targeting is the preferential accumulation of chemotherapeutic agents in solid tumors. Active targeting involves the chemical ‘decorating’ of the surface of drug carriers with molecules enabling them to be selectively attached to diseased cells.
Current research at the Nanotechnology Research Laboratory of the Faculty of Pharmacy, UiTM, involves the formulation of nanosystems intended for oral drug administration based on the following principles:
(i) the system must be stable in the gastrointestinal tract
(ii) it should interact with the intestinal epithelium and be absorbed therein
(iii) it should be made of safe materials.
Nanoparticles are prepared by the wet nanogrinding or precipitation methods. The size is determined by the Zetasizer and visualized by the scanning electron microscope. Among various drug molecules cefotaxime sodium (a peptide) has been selected as model drug to test the efficacy of the systems for oral administration of peptides. Interestingly, following oral administration to rats, these systems elicited higher drug levels, than control drug solutions. These results suggest that the polymeric nanosystems are able to enter the epithelia and provide a continuous delivery of the peptide to the blood stream.
Also, transdermal delivery systems (mainly for cosmetic application) are under study. They comprise nanoemulsions, solid lipid nanoparticles and nanostructured lipid particles for the delivery of active cosmetics into the skin. These nanocosmetic systems favour the transport of suitable lipids into the skin, increasing the skin bioavailability of the active compounds. This may reduce the transepidermal water loss (TEWL), indicating that the barrier function of the skin is strengthened.
The long-term objective of nanopharmacy is driven by the need to target drugs to the site of action, to increase patient acceptability and reduce healthcare costs; and on the other hand, to identify novel ways to deliver new classes of pharmaceuticals that cannot be effectively delivered by conventional means. The transition from research to commercial nanopharmacy is at a nascent stage of development. Although the full potential of nanopharmacy is distant, recent advances in nanopharmacy (dendrimers, nanoparticles, and oliposomes) and personalized medicine (a result of advances in pharmacogenetics and pharmacogenomics) is a further step on transforming nanopharmacy from research ideas into commercial reality.
Research Management Institute