Pulmonary drug delivery selectivity

Intimately related to these factors is the design of the device, formulation, and the interface with the patient. Much of the discussion below will focus on the implications of excipients on formulation challenges for inhaled aerosol products. This chapter summarizes excipients for pulmonary formulations from several perspectives (i) excipient selection based on principles of delivery, (ii) physicochemical requirements for excipients, and (iii) specific challenges for formulations faced with aerosol drug delivery systems, including (a) biological aspects, (b) microbiological aspects, (c) analytical issues, and (d) future prospects. 

F. Modulation of Pulmonary Selectivity by Sustained-release Drug Delivery Systems... 

Table 3 Selected Studies of Sustained Drug Delivery Systems for Pulmonary Delivery... 

The purpose of this chapter is to present overviews of a selection of the major endothelial and epithelial barriers to drug delivery for which there are either primary culture or cell line systems that recapitulate the characteristics of the in vivo barrier. Our objective is to define some general characteristics of cell culture models and highlight the more commonly applied primary cell cultures and cell lines in use today. Specifically, we focus on cell culture models for the intestinal epithelium, blood-brain barrier, pulmonary and nasal epithelium, ocular epithelium, placental barrier, and renal epithelium. Renal epithelium was included here primarily because some cell lines derived from this tissue [e.g., Madin-Darby canine kidney cells (MDCK)] are often used as surrogates for other barriers by pharmaceutical scientists. We have arbitrarily chosen to exclude the skin and liver from the scope of this overview. However, it should be noted that hepatocyte cell culture models, for example, are becoming more widely available and have been the subject of recent reviews.1,2... 

Alternate delivery systems are the focus of many laboratories throughout the world. The major routes selected are oral, pulmonary, intranasal, transdermal, vaginal, and others. Successful drug delivery discoveries are the result of interdisciplinary efforts of biochemists, chemists, engineers, physicists, pharmaceutical scientists, and clinical investigators. 

Solid lipid nanoparticles have been investigated in many different administration routes parenteral, oral, (trans)dermal, ocular d64,i97 pulmonary.Furthermore, cationic SLN formulations were used to complex DNA for cell transfection. In the following chapter, selected studies are summarized with respect to a parenteral, oral and dermal administration as well as for gene delivery to illustrate the versatility of solid lipid nanoparticle formulations in drug delivery. 

The delivery system plays a key role in determining the overall pulmonary deposition (percent of drug deposited in the lung), the amount of swallowed drug, and the regional deposition within the lung. All three factors are important for the degree of pulmonary selectivity. 

Selection of the appropriate route of administration and delivery device is critical for the commercial success of a drug product. Although injections are the most efficient delivery method for proteins, they are not always the most suitable from the patient s perspective. Few routes of administration (IV, IM, SC, pulmonary, and topical for local delivery) have been successful to date with protein therapeutics because of the size and complexity of the protein structure. Consideration of the bioavailability via a given route must be made when determining the dose required. Use of a delivery device such as an implantable pump, needle-free injector, or dry-powder inhaler may yield a product with a commercial advantage over a competitor s product. 

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