Advanced delivery system

The process of phagocytosis is of particular relevance when particulate delivery systems, such as microspheres, liposomes and other advanced delivery systems (described in Chapter 5), are used. Such particulate carriers are susceptible to MPS clearance. Sequestration by the MPS is useful in some cases, for example in the treatment of certain microbial diseases. However, if the drag is to be delivered to sites other than the MPS, it is highly undesirable. Therefore considerable research effort is being directed towards methods of avoiding MPS uptake of drag delivery systems. Strategies to both exploit and avoid MPS uptake are described in detail in Chapter 5 (see Section 5.1.4). 

In this book, the term dmg delivery system (DDS) is used as a general term to denote any type of advanced delivery system. Conventional dmg delivery systems are simple oral, topical or injection formulations. A DDS, as used here, represents a more sophisticated system which may incorporate one, or a combination, of advanced technologies such as rate-control, pulsatile release or bioresponsive release to achieve spatial and/or temporal delivery. A dmg delivery and targeting system (DDTS) specifically describes an advanced delivery system that incorporates some type of specific targeting technology (such as, for example, monoclonal antibodies) such systems are currently most advanced for use in the parenteral administration of dmgs. Also, rate-control and dmg targeting are treated as two separate issues in this book and are dealt with in detail in Chapters 4 and 5 respectively. 

Advanced delivery systems include transdermal patches, which are now well established and accepted by patients. Technologies under development include, for example, iontophoresis, which uses a small electric current to propel the drag through the skin. Drag delivery via iontophoresis occurs at enhanced rates and amounts in comparison to patch technology, which uses simple passive diffusion. The development of safe, non-toxic absorption enhancers to facilitate transdermal absorption is a further focus of current research. 

Davis, S. S. In Advanced Delivery Systems for Peptides and Proteins—Pharmaceutical Considerations Delivery Systems for Peptide Drugs Davis, S. S., Ilium, L., Tomlinson, E., Eds. Plenum Press New York, 1986, pp. 1-21. 

An alternative to the pulmonary route of administration is the nasal route, which is less demanding when it comes to formulation. With regard to, for example, particle size and simpler device development (5,90), examples are Minirin (Ferring), desmopression, and Suprecur (Sanofi-Aventis), buserelin, which are proteins formulated as nasal drops or nasal spray, where bioavailabdities of approximately 3% to 10% can be obtained. The formulations are just protein dissolved in purified water containing preservatives chlorbutanol and benzalkonium chloride (91,92). However, more advanced delivery systems are also used, for example, chitosan formulations where bioavailabihties of 14% to 15% compared to subcutaneous administration can be obtained (90). A recent review by nium (2007) gives more details on nanoparticulate systems used for nasal delivery (93) or consult Costantino et al. (2007) on the physiochemical and therapeutic aspects (5). 

Advancing technology as well as this demonstration of potential utility of Mass Scatter able Mines led the Army to revise mine warfare doctrine and establish new requirements for a family of Scatterable Mines that could be rapidly and remotely emplaced by a variety uf delivery systems. This requirement called for both Anti-Tank and Anti-Personnel Mine Systems. To this end, two first generation systems are well ad-vandedin devebpment. These are the XM56, a helicopter delivered Anti-Tank Mine System and die XM692, an artillery delivered Anti-Personnel Mine System. Other second generation systems which add increased versatility and capability are scheduled to follow ... 

Edwards-Levy, F., Andry, M. C. Levy, M. C. (1994). Determination of free amino group content of serum-albumin microcapsules. II. Effect of variations in reaction-time and terephthaloyl chloride concentration. International Journal of Pharmaceutics, Vol. 103, 3, (March 1994), pp. (253-257), ISSN 0378-5173 Friend, D. R. (2005). New oral delivery systems for treatment of inflammatory bowel disease. Advanced Drug Delivery Reviews, Vol. 57, 2, (January 2005), pp. (247-265), ISSN 0169-409X... 

Liu, Z., Jiao, Y., Wang, Y., Zhou, C. Zhang, Z. (2008). Polysaccharides-based nanoparticles as drug delivery systems. Advanced Drug Deliver / Reviews, Vol. 60, 15, (December 2008), pp. (1650-1662), ISSN 0169-409X... 

Schacht E, Vandorpe J, Crommen J, Seymur L (1996) In Ogata N, Kim SW, Feijen J, Okano T (eds) Advanced biomaterials in biomedical engineering and grug delivery systems. Springer, Tokyo, p 81... 

T., Katutani, Y., and Kitsugi, T., Release of antibiotics from composites of hydroxyapatite and poly(lactic acid), in Advances in Drug Delivery Systems (J. M. Anderson and S. W. Kim, eds.), Elsevier, New York, 1986, pp. 179-186. 

Peritonitis is a leading cause of morbidity in PD patients, which often leads to loss of the catheter and subsequent change to HD as the treatment modality. However, recent advances with connectors used during instillation and drainage of dialysate and delivery systems have dramatically decreased the incidence of peritonitis. Peritonitis can be caused by chemical irritation or microorganisms. 

To facilitate in-plant compounding, most suppliers have developed systems which efficiently and repro-ducibly deliver a controlled additive package to a compound, using either a specialised concentrate or a masterbatch formulation. Some of the polymer manufacturers have also made available advanced additive delivery systems, which they have often developed originally for their own use (e.g. Eastman, Montell). 

As pharmaceutical scientists gain experience and tackle the primary challenges of developing stable parenteral formulations of proteins, the horizons continue to expand and novel delivery systems and alternative routes of administration are being sought. The interest in protein drug delivery is reflected by the wealth of literature that covers this topic [150-154]. Typically, protein therapeutics are prepared as sterile products for parenteral administration, but in the past several years, there has been increased interest in pulmonary, oral, transdermal, and controlled-release injectable formulations and many advances have been made. Some of the more promising recent developments are summarized in this section. 

GM Zentner, GS Rork, KJ Himmelstein. Osmotic flow through controlled porosity films An approach to the delivery of water soluble compounds. In JM Anderson, SW Kim, eds. Advances in Drug Delivery Systems. New York Elsevier, 1986, pp 217-230. 

Kostarelos, K. (2003) Rational design and engineering of delivery systems for therapeutics biomedical exercises in colloid and surface science. Advances in Colloid and Interface Science, 106, 147-168. 

Recent developments in polymer chemistry have allowed for the synthesis of a remarkable range of well-defined block copolymers with a high degree of molecular, compositional, and structural homogeneity. These developments are mainly due to the improvement of known polymerization techniques and their combination. Parallel advancements in characterization methods have been critical for the identification of optimum conditions for the synthesis of such materials. The availability of these well-defined block copolymers will facilitate studies in many fields of polymer physics and will provide the opportunity to better explore structure-property relationships which are of fundamental importance for hi-tech applications, such as high temperature separation membranes, drug delivery systems, photonics, multifunctional sensors, nanoreactors, nanopatterning, memory devices etc. 

Silica particles A novel drug-delivery system. Advanced Materials, 16, 1959-1966. 

O Hagan DT (1998) Recent advances in immunological adjuvants the development of particulate antigen delivery systems. Exp Opin Invest Drugs 7 349-359... 

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