Site-specific drug release

Drug delivery Site-specific delivery of drugs. Ideally, these NPs could bear a pharmaceutical drug that could be driven to the target organ and be released there. 

Drugs, cosmetic ingredients, and food additives are microencapsulated for a variety of reasons, which include reducing local side-effects, controlled release, site-specific (drug) delivery, and drug targeting. A tremendous amount of research work has been done in a search for suitable methods to achieve an effective eneapsulation of water-soluble active matter. The physical characteristics of the microspheres produced largely determine their suitability for use for different objectives. Microspheres are prepared from both natural and synthetic polymers. 

One element that is often ignored in this evaluation though is the extent of the mechanism. For example, if enzymatic activity is to be used to release drug at the site of action, even if the activity/time/volume is one hundred times higher at the desired site than elsewhere (not unreasonable), but the volume of nonspecific activity is one thousand times as great (also not unreasonable), the system does not stand any chance of achieving site-specific delivery. 

Controlled release, although resulting in a zero-order delivery system, may also incorporate methods to promote localization of the drug at an active site. In some cases, a controlled-release system will not be sustaining, but will be concerned strictly with localization of the drug. Site-specific systems and targeted-delivery systems are the descriptive terms used to denote this type of delivery control. 

In addition, biodegradable nanoparticles for sustained release formulations to improve site-specific drug delivery has also been reviewed [98]. 

III. Metabolism Issues here include species-specific metabolism (related to novel pattern of drug release at receptor sites), and possible use of novel paracrine- and endocrine-like peptidergic mediators. These could manifest themselves in novel ... 

Cellular Carriers. Erythrocytes, leukocytes, platelets, islets, hepatocytes, and fibroblasts have all been suggested as potential carriers for drugs and biological substances. They can be used to provide slow release of entrapped drugs in the circulatory system, to deliver drugs to a specific site in the body, as cellular transplants to provide missing enzymes and hormones (in... 

When administered as valaciclovir, aciclovir is released during absorption, and 60% of the drug reaches the bloodstream, as described above. Site activation also occurs in herpesvirus-infected cells where aciclovir is biochemically transformed to the phosphorylated active drug by virus-specific thymidine kinase [74]. 

Implementation of dissolution testing by BP was in a tiered program similar to that employed at the time by USP. For the first category, products would conform to 75% release in 45 min. Where the drug had a narrow therapeutic index and should not release too rapidly, was known to exhibit a brief plasma half-life, or have site-specific absorption, additional testing to satisfy the need for greater control would be considered. Dissolution tests were included in 1980 for 14 tablet and four capsule monographs (15,16). 

Thermoresponsive polymeric micelles with PIPAAm block copolymers can be expected to combine passive spatial targeting specificity with a stimuli-responsive targeting mechanism. We have developed LCSTs of PIPAAm chains with preservation of the thermoresponsive properties such as a phase transition rate by copolymerization with hydrophobic or hydrophilic comonomers into PIPAAm main chains. Micellar outer shell chains with the LCSTs adjusted between body temperature and hyperthermic temperature can play a dual role in micelle stabilization at a body temperature due to their hydrophilicity and initiation of drug release by hyperthermia resulting from outer shell structural deformation. Simultaneously, micelle interactions with cells could be enhanced at heated sites due... 

A buccal drug delivery system is applied to a specific area on the buccal membrane. Moreover, the delivery system ean be designed to be unidirectional in drug release so that it can be protected from the loeal environment of the oral cavity. It also permits the inclusion of a permeation enhancer/protease inhibitor or pH modifier in the formulation to modulate the membrane or the tablet-mucosal environment at that particular application site. While the irritation is limited to the well-defined area, the systemic toxicity of these enhancers/inhibitors and modifiers can be reduced. The buccal mucosa is well suited for this type of modification as it is less prone to irreversible damage [9]. In the event of drug toxicity, delivery can be terminated promptly by removal of the dosage form. 

In the design of drugs, the usefulness of renal-specific enzymes which enable the site-specific release of the active drug, should be taken into account. The design of kidney-selective prodrugs is based upon the relatively higher amounts of certain enzymes in the proximal tubular cells than elsewhere in the body. 

---