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Pharmaceutical Nanobiotechnology: Drug Targeting, Gene Delivery and Tissue Engineering
- 등록일2003-07-24
- 조회수10285
- 분류산업동향 > 종합 > 종합
Pharmaceutical Nanobiotechnology: Drug Targeting, Gene Delivery and Tissue Engineering
Claus-Michael Lehr
Dept. of Biopharmaceutics and Pharm. Technology,
Saarland University, Saarbrucken, Germany,
email: lehr@mx.uni-saarland.de, http://www.uni-saarland.de/fak8/lehr
Pharmaceutical nano-biotechnology has an enormous potential to improve the delivery of drugs across biological barriers, both for local as well as for systemic application. This holds in particular for macromolecular biopharmaceuticals (peptides, proteins, antisense agents, gene vectors), but also for conventional small organic molecules.
In order to improve the delivery of macromolecules, we are exploring the potential of specific bioadhesive ligands, in particular lectins and lectin-like molecules (1). Currently, we are using computer-aided modeling and docking, as well as atomic force micros to calculate and measure binding forces, respectively, relevant to the design of structurally optimized lectinomimetics for controlled cellular targeting and delivery (2). Such ligands may be coupled to the surface of nanoparticles, prepared from lipids, polymers or inorganic materials, representing an alternative to viral gene vectors, and allowing targeted delivery of drugs to specific areas of mucosal epithelia.
Advanced drug carriers for pulmonary drug delivery
Based on several clinical studies, the respiratory mucosa of the peripheral lung appears as a promising new route for the systemic delivery of peptides and proteins, and the first commercial inhalative formulations of insulin are expected to be available soon. Still, however, the mechanisms how macromolecules can cross the so-called “blood-air barrier” are hardly understood, which makes a rational optimisation of drug carriers for such purposes difficult. In order to study transport processes and the interaction of drug carriers with the respiratoy mucosa at cellular level, we developed a method to grow human alveolar epithelial type cells (HAEpC) on permeable filters in primary culture, forming a confluent monolayer with functional tight junctions (3). While at present no permanent cell line seems to be suitable to study drug transport at the alveolar epithelium, some cell lines derived from airway epithelial cells can be used for pharmaceutical investigations, depending on the culture conditions (4).
Chemically modified SiO2-Nanoparticles as non viral gene delivery systems
Cationic silica nanospheres (SiNP) were obtained by covalent modification of commercial SiO2 -colloids with aminoalkylsilanes1,2. The size could be varied between 10 and 100 nm and a positive zeta potential of more than +31 mV at pH 7.4 was be obtained (5, 6). Such cationically surface modified silica nanoparticles form stable complexes with DNA under physiological conditions and are able to transfect epithelial cells in vitro with marker genes. Observed Transfection rates were comparable to those observed with other non-viral gene transfer systems (e.g. pEI and other polymers.) Surprisingly, the cytotoxicity of the Silicananoparticles was much lower than for other systems, which underscores the favorable safety profile of this new technology platform for gene delivery.
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