Drug delivery systems parenteral administration route

The lack of activity after oral administration for most peptides and proteins resulted in the past besides parenteral application into the utilization of nonoral administration pathways, for example, nasal, buccal, rectal, vaginal, percutaneous, ocular, or pulmonary drug delivery [27]. Drug delivery via these administration routes, however, is also frequently accompanied by presystemic degradation processes. Bioavailability of numerous peptides and proteins is, for example, markedly reduced after subcutaneous or intramuscular administration compared to their intravenous administration. The pharma-cokinetically derived apparent absorption rate constant is thus the combination of absorption into the systemic circulation and presystemic degradation at the absorption... 

Table 6.5 List of mucoadhesive polymers in the design of nano-drug delivery systems for administration by non-parenteral routes [58, 59]...

The use of ttaditional disperse systems, e.g., macroemulsions, in the pharmaceutical industry has been limited due to manufacturing complexity and stability problems [117]. The characteristic properties of nano-emulsions (kinetic stability, small and controlled droplet size, etc.) make them interesting systems for pharmaceutical applications. Indeed, nano-emulsions are used as drug delivery systems for administration through various systemic routes. There are numerous publications on nano-emulsions as drug delivery systems for parenteral [17,18,28,29,118-124], oral [25,125-129], and topical administration, which includes the administration of formulations to the external surfaces of the body skin [32,130,131] and to the body cavities nasal [30,132] as weU as ocular administration [31,133-136]. Moreover, many patents concerning pharmaceutical applications of nano-emulsions have been registered [17,18,25,137-145]. An application of nano-emulsions in this field has been in the development of vaccines [33,146-147]. 

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. 

Duma RJ, Akers MJ, Turco SJ. Parenteral drug administration routes, precautions, problems, complications, and drug delivery systems. Chapter 2. In Avis KE, Lieberman HA, Lachman L, eds. Pharmaceutical Dosage Forms Parenteral Medications. 1. New York Marcel Dekker, Inc., 1992. 

Parenteral administration is the primary route of testing delivery for nucleic acid therapeutics irrespective of whether systemic or local effects are desired. However, to some extent, pulmonary and oral routes are also investigated as potential routes for local targeting to treat cystic fibrosis or colonic tissue (171-173). For nonparenteral delivery, the use of pharmaceutical excipients in the formulation is critical. In addition, the production costs of nucleic acid therapeutic-containing drug delivery systems should be minimized. Even for intravenously or subcutaneously injected nucleic acid-based therapeutics, the use of protective carriers is most likely necessary, and advantageous as compared to injection of the naked RNA or DNA. Carriers can be divided into viral or... 

Ingemann, I. et al. Peptide and protein drug delivery systems for non-parenteral routes of administration. In Pharmaceutical Formulation Development of Peptides and Proteins. Frokjaer, S. and Hovgaard, L. (Eds.) Taylor Francis, London, U.K., 2000, p. 189. 

Sporadic clinical reports, without the support of data from controlled studies, repeatedly indicate the effectiveness of intratracheal administration of parenteral antimicrobial preparations in the treatment of tracheobronchitis and pneumonia in cattle. The expectation when using this route of administration is that a greater therapeutic effect will be achieved when the drug is placed as close to the infection site as possible, rather than relying on the systemic circulation for drug delivery. 

Polylactic acid has been studied extensively for controlled release applications ranging from the oral delivery of simple drugs such as indomethacin9 to the parental administration of complex proteins such as insulin.10 Polylactic acid of different molecular weights has been studied as matrix material for parenteral administration. Seki et al.11 used polylactic acid 6000 and Smith and Hunneyball8 used polylactic acid 100,000 for the controlled delivery of drugs by the parenteral route. Several polylactic acid systems have been studied for the controlled... 

Several types of CDD systems have been designed based on various mechanisms of drug release (Table I). These mechanisms are dependent on the required site of drug delivery, the physicochemical properties of the drug and also of the delivery vehicle (13), Modes of administration can be oral, sublingual, transdermal, rectal, intrauterine, ocular, or parenteral (intramuscular, peritoneal, and subcutaneous routes of injection). 

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