Drug Delivery Systems

A perspective drug delivery systems can be defined as mechanisms to introduce therapeutic agents into the body. Chewing leaves and roots of medical plants and inhalation of soot from the burning of medical substances are examples of drug delivery from the earliest times. However, these primitive approaches of delivering drugs lacked a very basic need in drug delivery; that is, consistency and uniformity (a required drug dose). This led to the development of different drug delivery methods in the later part of the eighteenth and early nineteenth century. Those methods included pills, syrups, capsules, tablets, elixirs, solutions, extracts, emulsions, suspension, cachets, troches, lozenges, nebulizers, and many other traditional delivery mechanisms. Many of these delivery mechanisms use the drugs derived from plant extracts. The modern era of medicine development started with the discovery of vaccines in 1885 and techniques for purification of drugs from plant sources in the late nineteenth century, followed by the introduction of penicillin after its discovery in 1929, and a subsequent era of prolific drug discovery. The development and production of many pharmaceuticals involves the genetic modification of microorganisms to transform them into drug-producing factories. Examples are recombinant deoxyribonucleic acid (DNA), human insulin, interferon [for the treatment of acquired immunodeficiency syndrome (AIDS) related Kaposi’s sarcoma, Hairy cell leukemia, Hepatitis B and C, etc.], interleukin-2 (Renal cell and other carcinomas), erythropoietin (for the treatment of anemia associated with chronic renal failure/AIDS/antiretroviral agents, chemotherapyassociated anemia in nomnyloid malignancy patient), and tissue plasminogen activator (1). It is now possible to produce oligonucleotide, peptide, and protein drugs in large quantities, while gene therapies also appear to be clinically feasible. Each of these therapeutic agents, by virtue of size, stability,ortheneedfortargeting,requiresaspecializeddrug delivery system (2). While the conventional drug delivery forms are simple oral, topical, inhaled, or injections, more sophisticated delivery systems need to take into account pharmacokinetic principles, specific drug characteristics, and variability of response from one person to another and within the same person under different conditions. The efficacy of many therapeutic agents depends on their action on target macromolecules located either within or on the surface of particular cells types. Many drugs interact with enzymes or other macromolecules that are shared by a large number of cell types, while most often a drug exerts its action on one cell type for the desired therapeutic effect. Certain hormones, for example, interact with receptor mechanisms that are present in only one or a few cell types. An ideal gene delivery system should allow the gene to find its target cell, penetrate the cell membrane, and enter into the nucleus. Further, genes should not be released until they find their target and one has to decide whether to release the genes only once or repeatedly through a predetermined way (2). Thus, the therapeutic efficacy of a drug can be improved and toxic effects can be reduced by augmenting the amount and persistence of drugs in the vicinity of the target cells, while reducing the drug exposure to the nontarget cells. This basic rationale is behind controlled drug delivery. A controlled drug delivery system requires simultaneous consideration of several factors, such as the drug property, route of administration, nature of delivery vehicle, mechanism of drug release, ability of targeting, and biocompatibility. These have been summarized in Fig. 1. It is not easy to achieve all these in one system because of extensive independency of these factors. Further, DRUG DELIVERY SYSTEMS 437