Multifunctional nanocarriers☆
Section snippets
Brief introduction
The use of nanoparticulate pharmaceutical carriers to enhance the in vivo efficiency of many drugs well established itself over the past decade both in pharmaceutical research and clinical setting. Surface modification of pharmaceutical nanocarriers, such as liposome, micelles, nanocapsules, polymeric nanoparticles, solid lipid particles, niosomes and others [1], [2], [3], [4] is normally used to control their biological properties in a desirable fashion and make them to simultaneously perform
Basic property of pharmaceutical nanocarriers – longevity in the blood
Since for the body defence system, “plain” pharmaceutical nanocarriers usually represent foreign particles, they become easily opsonized and removed from the circulation long prior to completion of their function. Thus, the “basic” property of any multifunctional nanocarrier is its longevity, and long-circulating pharmaceuticals and pharmaceutical carriers represent currently an important and still growing area of biomedical research, see for example [7], [8], [9], [10], [11], [12]. There are
Combination of targeted ligands with protecting polymers
The further development of the concept of pharmaceutical nanocarriers involves the attempt to add the property of the specific target recognition to the carrier's ability to circulate long, i.e. simultaneously attach both the protecting polymer and the targeting moiety on the surface of the nanocarrier. Targeting of drug carriers with the aid of ligands specific to cell surface-characteristic structures allows for the selective drug delivery to those cells. To obtain “simple” targeted
Adding the stimuli sensitivity function
An additional function can be added to long-circulating PEGylated pharmaceutical carriers, which allows for the detachment of protecting polymer (PEG) chains under the action of certain local stimuli characteristic of pathological areas, such as decreased pH value or increased temperature usually noted for inflamed and neoplastic areas. The matter is that the stability of PEGylated nanocarriers may not always be favorable for drug delivery. In particular, if drug-containing nanocarriers
The function for intracellular delivery of nanocarriers
Many biologically active compounds, including macromolecular drugs, need to be delivered intracellularly to exert their therapeutic action inside the cell onto nucleus or other specific organelles, such as mitochondria. This group includes preparations for gene and antisense therapy, which have to reach cell nuclei; pro-apoptotic drugs, which target mitochondria; lysosomal enzymes, which have to reach lysosomal compartment; and some others. However, the lipophilic nature of the biological
Contrast moiety for visualization
To make it possible to use pharmaceutical nanocarriers for diagnostic/imaging purposes as well as to allow for their real-time biodistribution and target accumulation, the contrast reporter moieties can be added to multifunctional nanocarriers. Currently used medical imaging modalities include: (a) Gamma-scintigraphy (based on the application of gamma-emitting radioactive materials); (b) Magnetic resonance (MR, phenomenon involving the transition between different energy levels of atomic nuclei
Some chemical reactions used to provide pharmaceutical nanocarrier with multiple functions
As clearly follows from everything said above, preparing multifunctional nanocarriers with controlled properties require the conjugation of proteins, peptides, polymers, cell-penetrating moieties, reporter groups and other functional ligands to the carrier surface (although, in certain cases functional components may be load inside the nanocarrier or distributed within the nanocarrier structure). This attachment can proceed non-covalently, via the hydrophobic adsorption of certain intrinsic or
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This review is part of the Advanced Drug Delivery Reviews theme issue on “Particulate Nanomedicines” Vol. 58/14, 2006.