Challenges and solutions for the delivery of biotech drugs – a review of drug nanocrystal technology and lipid nanoparticles
Introduction
The introduction of biotechnological methods for the production of drugs brought a revolution to the pharmaceutical field. Nowadays, drugs like insulin are produced by recombinant technology. This reduces not only the price for injectables but makes it simultaneously so relatively cheap that enough insulin is available at a sufficiently low price to go for other, more patient friendly administration routes, i.e. pulmonary delivery. After pulmonary delivery, the bioavailability of insulin is much lower compared to injection (only approximately 10% (Brunner et al., 2001, Heinemann et al., 2000)), thus requiring higher amounts of insulin for treatment. Therefore, development of pulmonary administration was only possible after insulin was available in sufficient, relatively low price quantity as provided by biotechnological production. At present, the clinical trials are in phase 3 with the products AERx (Novo Nordisk/Aradigm) and Exubera (Aventis/Pfizer/Inhale). Of course other recombinant products are still more expensive than the natural products (e.g. albumin), but some of the natural sources are limited, in addition safety aspects are also of importance (e.g. potential contamination from blood products).
One has to differentiate between two different types of drugs:
- 1.
Biopharmaceutical drugs (biopharmaceuticals) and
- 2.
Biotechnological drugs.
- 1.
Water-soluble drugs (in general biopharmaceuticals) and
- 2.
Poorly water-soluble drugs (many products from biotechnological processes, e.g. aphidicolin).
Section snippets
Challenges for formulation and delivery
Of course, the challenges are manifold, basically one can differentiate between problems being very often related to these drugs and problems being more related specifically to a molecule, e.g. conformation issues. Problems frequently occurring with many drugs are:
- 1.
Poor solubility
- 2.
Insufficient in vitro stability (shelf life)
- 3.
Too low bioavailability
- 4.
Too short in vivo stability (half life)
- 5.
Strong side effect, need for targeted delivery
- 6.
Regulatory issues/hurdles
- 7.
Lack of large scale production
Solutions for optimised delivery of biotechnology drugs
Traditional administration routes are oral administration or parenteral injection. The orally administered drug is absorbed from the gut and enters the blood stream, diffuses from the enteral absorption sides to blood and tissue whereas a parenterally administered drug is injected directly into the blood, which is typically only possible in form of a drug solution or emulsion. By these routes of drug administration, the drug itself is present as molecule in a solution (i.e. blood). It
Conclusion and perspective
The presented carriers are suitable to solve delivery problems with biotech drugs of different solubility. The suitability of the carriers has been proven because they are either already on the market (e.g. drug nanocrystals in products such as Rapamune® or Emend®) or they have been used in clinical phases/human studies (cyclosporine-loaded SLN). They fulfill the key prerequisites for the introduction to the clinic and the market, that means they are in line with regulatory requirements and
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