Nanoparticulate drug carriers include a class of particles made of polymers or lipids that — because of their size and chemical
composition —permit systemic and local treatment.
In general, these systems are expected to protect a drug from degradation, enhance drug absorption by facilitating diffusion
through epithelium, modify the pharmacokinetic and drug tissue distribution profile and/or improve intracellular penetration
They can be administered by all possible routes of administration, generally improving both bioavailability and therapeutic
efficacy of the carried drug.3 They represent an alternative class of vehicles to liposomes to transport drugs straight to the targeted diseased cells
in the body.
Table 1 Definition of the different types of nanoparticulate drug carriers and schematic representations.4–18
Numerous types of nanoparticle drug carriers have been developed (Table 1). The range of applications includes the treatment
of all major public health diseases including severe infections and cancer. They are also strongly believed to potentially
solve the problem of the in vivo delivery of biomimetic molecules such as nucleic acids, proteins, peptides and very insoluble drugs, which is very difficult
by other means (Table 2).
Although several liposomal formulations have been marketed since 1995 — illustrating that nanotechnology can be used to administer
toxic drugs such as antifungal and anticancer agents — two new formulations for polymer nanoparticles entered clinical trials
recently for cancer therapy.
This article focuses on the development of nanoparticulate drug carriers, highlighting several of the key issues being addressed
up to now.
Table 2 Suggested nanoparticulate drug carriers as a function of the physicochemical characteristics of the drug to be administered.3–31
The design of nanoparticulate drug carriers must fulfil the following requirements:
- Composition must be acceptable for use in human therapy (biodegradable, biocompatible, nontoxic).
- Size must be suitable for administration to humans by different routes and allow diffusion inside the body to reach the biological
- The biodistribution should suit the therapeutic target.
- The carrier must be loaded with the drug and should only release the drug in a controlled manner once the carrier has reached
the biological target site.
As lipids are part of living constituents, they were considered to be suitable chemicals to formulate solid lipid nanoparticles
(SLNs) and nanocapsules (LNCs) (Tables 1 and 2).
Synthetic polymers offer an almost infinite array of chemical composition and structure combinations. However, only a few
have the requirements that make them useful as nanoparticulate drug carriers.
The prime candidates are polyesters including polylactide (PLA) derivatives and polyepsiloncaprolactone (PCL), polyalkylcyanoacrylate
(PACA) and corresponding copolymers with polyethylene glycol (PEG), polysaccharides and polyethylenimine (Tables 1 and 2).
Natural macromolecules including polysaccharides (chitosan, alginate, pectine) were introduced to formulate hydrogel nanoparticles.
Research is continuing to find suitable new polymers because polymers can be produced at lower cost than lipids and should
be more interesting (economically) based on economic considerations.32 Polyesters of polymalic acid, polyamino acids of polybenzyl-glutamate) and pH- or temperature-sensitive species are growing