Drug Delivery- Recombinant Human Deoxyribonuclease I

 DRUG DELIVERY

 

The droplet or particle size of an aerosol is a critical factor in defining the site of deposition of the drug in the patient’s airways (Gonda, 1990). A distribution of particle or droplet size of 1 to 6 µm was determined to be optimal for the uniform deposition of rhDNase I in the airways (Cipolla et al., 1994). Jet nebulizers have been used since they are the simplest method of producing aerosols in the desired respirable range. However, recirculation of protein solutions under high shear rates in the nebulizer bowl can present risks to the integrity of the protein molecule. rhDNase I survived recirculation and high shear rates during the nebulization process with no apparent degrada-tion in protein quality or enzymatic activity (Cipolla et al., 1994).

 

Approved nebulizers produce aerosol droplets in the respirable range (1–6 µm) with a mass median aerodynamic diameter (MMAD) of 4 to 6 µm. The delivery of rhDNase I with a device that produces smaller droplets leads to more peripheral deposition in the smaller airways and thereby improves efficacy (Geller et al., 1998). Results obtained in 749 CF patients with mild disease confirmed that patients randomized to the Sidestream nebulizer powered by the Mobil Aire Compressor (MMAD ¼ 2.1 µm) tended to have greater improvement in pulmonary function than patients using the Hudson T nebulizer with PulmoAide Compressor (MMAD ¼ 4. µm). These re-sults indicate that the efficacy of rhDNase I is dependent, in part, on the physical properties of the aerosol produced by the delivery system.

Comments

Post a Comment

Popular posts from this blog

Adenoviral Vectors - Viral Vectors for Gene Transfer

Image
  Viral Vectors for Gene Transfer   Viruses, natural parasites that efficiently enter cellular targets and hijack cellular machinery for propagation, are currently the most effective vectors for gene therapy. Approximately 70% of all gene therapy clinical trials employ viral vectors (Table 4). Many viruses with divergent properties have been devel-oped for gene transfer. Retroviruses, adenoviruses and adeno-associated viruses (AAVs) are the most extensively studied to date. Characteristics of each are summarized in Table 5.   Adenoviral Vectors Biology   Adenoviruses are non-enveloped, lytic, DNA viruses with a linear double-stranded genome and icosahedral symmetry. Since the isolation of the first human adenovirus in 1953 from tonsils and adenoid tissue (Rowe, 1953), 50 additional serotypes have been identified and grouped into six species (A–F) based on genome size, composition and homology, hemag-glutinating properties and oncogenicity in rodents. Because the subg...
Read more

Direct Binding to Non-Nucleic Acids

Image
  DIRECT BINDING TO NON-NUCLEIC ACIDS The ability of nucleic acids to fold into complex three-dimensional structures through regions of (partial) complementarity allows them to bind to virtually any molecule with nano- to picomolar affinity (Proske et al., 2005). This high affinity is supported by data on their extreme specificity. A nucleic acid sequence specifically binding theophylline has a million times higher affinity for theophylline than caffeine, mole-cules which differ by only one methyl group.   Aptamers/Riboswitches   Aptamers and riboswitches are single-stranded ONs of either DNA or RNA, generally about 60 nucleotides long, which fold into well-defined three-dimensional structures. They bind to their target molecule by complementary shape interactions accompanied by charge and hydrophobic interactions and hydrogen bridges. The target can be small molecules or macromolecules. Aptamers are isolated artificially, whereas riboswitches occur naturally (Tucker and ...
Read more

Uptake - Immunological Principles of Vaccines

  Uptake   Every immune reaction against a pathogen starts with its uptake by specialized phagocytic cells in the infected tissue. These cells carry receptors on their surface; pattern-recognition receptors (PRRs) that recognize common features of pathogens called pathogen associated molecular patterns (PAMPs). Binding of PAMPs to these PRRs results in phagocy-tosis of the pathogens. Examples of PRRs are toll-like receptors (TLRs), scavenger receptors and C-type lectins (Table 2). TLRs consist of a family of receptors, with each member recognizing different patterns on the surface of pathogens ( Akira et al., 2006). TLRs canbe found on many cells including macrophages and dendritic cells (DCs). DCs can also engulf materials from their extracellular environment by a receptor independent process called micropinocytosis.
Read more