Therapeutic agents delivery system

Eroglu M, Irmak S, Acar A, Denkba EB (2002) Design and evaluation of a mucoadhesive therapeutic agent delivery system for postoperative chemotherapy in superficial bladder cancer. Int J Pharm 235(l-2) 51-59... 

Membrane-reservoir systems based on solution-diffusion mechanism have been utilized in different forms for the controlled delivery of therapeutic agents. These systems including membrane devices, microcapsules, liposomes, and hollow fibres have been applied to a number of areas ranging from birth control, transdermal delivery, to cancer therapy. Various polymeric materials including silicone rubber, ethylene vinylacetate copolymers, polyurethanes, and hydrogels have been employed in the fabrication of such membrane-reservoir systems (13). 

The selection of a vehicle can dramatically affect delivery and consequently efficacy of topical preparations. In terms of transdermal delivery, where delivering therapeutic agents for systemic effects is desired, solvents and co-solvent systems are widely used to improve both the amount and range of drugs that can be administered at therapeutic levels through the skin. Vehicles used in transdermal systems, such as patches, have recently been reviewed (Williams, 2003). In contrast, the focus of this chapter is on the use of solvents in topical dosage forms, i.e. preparations intended for a local or regional effect on the skin. 

Currently, polymeric micelles are widely accepted as drug and imaging agent delivery systems due to their ease of formation, stability, ability to encapsulate hydro-phobic molecules and therapeutic success in preclinical and clinical studies [88]. 

Some of their derivatives have been used as antiviral drugs. Due to their flexible chemistry, they can be exploited to design drug delivery systems and in molecular nanotechnology. In such systems, they can act as a central lipophilic core and different parts like targeting segments, linkers, spacers, or therapeutic agents can be attached to the said central nucleus. Their central core can be functionalized by peptidic and nucleic acid sequences and also by numerous important biomolecules. 

The promise of the isolation and production of therapeutic polypeptides and proteins demands that for treatment of a chronic disease state an oral delivery system be developed which will protect these valuable agents from the hostile gastric environment. Subsequently, the drugs will have to be completely released in the intestine, preferably in a state that will enhance their rapid dissolution and transport across the gut wall minimizing interaction with intestinal proteases. 

The conventional concentration of benzalkonium chloride in eyedrops is 0.01%, with a range of 0.004-0.02% [111]. While uptake of benzalkonium chloride itself into ocular tissues is limited [113], even lower concentrations of benzalkonium chloride have been reported to enhance corneal penetration of other compounds including therapeutic agents [93,112,114]. The differential effect of this preservative on the cornea compared to the conjunctiva can be exploited to target a drug for corneal absorption and delivery to the posterior segment of the eye [115]. Its use has been proposed as a means of delivering systemic doses by an ocular route of administration [116]. 

Controlled and sustained drug delivery has recently begun to make an impression in the area of treatment of dental diseases. Many researchers have demonstrated that controlled delivery of antimicrobial agents, such as chlorhexidine [128-130], ofloxacin [131-133], and metronidazole [134], can effectively treat and prevent periodontitis. The incidence of dental caries and formation of plaque can also be reduced by controlled delivery of fluoride [135,136]. Delivery systems used are film-forming solutions [129,130], polymeric inserts [132], implants, and patches. Since dental disease is usually chronic, sustained release of therapeutic agents in the oral cavity would obviously be desirable. 

Despite the evidence for the cytotoxicity of CNTs, there are an increasing number of published studies that support the potential development of CNT-based biomaterials for tissue regeneration (e.g., neuronal substrates [143] and orthopedic materials [154—156]), cancer treatment [157], and drug/vaccine delivery systems [158, 159]. Most of these applications will involve the implantation and/or administration of such materials into patients as for any therapeutic or diagnostic agent used, the toxic potential of the CNTs must be evaluated in relation to their potential benefits [160]. For this reason, detailed investigations of the interactions between CNTs/CNT-based implants and various cell types have been carried out [154, 155, 161]. A comprehensive description of such results, however, is beyond the scope of this chapter. Extensive reviews on the biocompatibility of implantable CNT composite materials [21, 143, 162] and of CNT drug-delivery systems [162] are available. 

The potential of the chemically modified nucleic acid molecules has been proven by in vitro studies however, the in vivo therapeutic applicability of these molecules seems to be unsatisfactory because of their possible toxic effects (largely unknown) and adverse bioavailability. In this view, both antisense and transfection technologies require reliable and efficient systems for their delivery into target cells. On the basis of this consideration, the development of an efficient nucleic acid delivery system represents one of the key steps for these therapeutic agents, which are necessary for a practical clinical utilization of natural or unnatural oligonucleotides. 

Constant release is not always the desired solution for controlled drug administration some therapeutic situations require consecutive pulses. A biphasic oral delivery system able to release an immediate dose of therapeutic agent as well as a further pulse of drug after some hours would, useful. In order to obtain such a desired release performance, a new system (three-layer tablet) has been designed with the following characteristics ... 

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