New Drug Delivery Systems in Anesthesia

The healthcare field has recently seen changes in drug delivery systems as a result of a movement to improve the efficacy of existing systems while lowering side effects [1].Drug delivery systems are useful in delivering the required amount of drugs efficiently to specific target sites. This allows them to increase bioavailability and absorption of molecules, sustain levels for long-term treatment, and decrease the total amount of drugs and doses required for patients, as well as the damage to normal tissues [1].

Intranasal delivery allows direct delivery to the cerebrospinal fluid conveniently and painlessly, with hardly any loss in bioavailability [2]. This is because most anesthetics can easily pass through the mucous membrane, and nasal delivery allows a way for them to completely bypass the blood-brain barrier [2, 3].

Pulmonary drug delivery systems include metered dose inhalers, nebulizers, and dry powder inhalers, which all offer the advantages of larger surface area and proximity to blood flow [4]. There has been a strong effort to develop a way to deliver opioids by inhalation, which has the benefit of increasing patient compliance, since the doses would be lower and less burdensome [1].

Buccal mucosal delivery systems, which consist of drug absorption through the membrane in the inner lining of the cheeks and the bottom of the mouth, are beneficial because they allow drugs to avoid being metabolized through the “first pass effect,” therefore decreasing the amount of the drugs that are needed [5]. While it generally has a slower onset because the buccal mucous is less permeable, it has been proven effective in delivering fentanyl and buprenorphine hydrochloride [6].

Intra-articular drug delivery systems, referring to delivery in the tissue between joints, are thought to prolong the residence time of drugs because of the presence of microspheres that are designed to improve uptake in these areas [7].

Transdermal delivery systems, patches worn on the skin, have been shown to bypass the first pass effect, keep drug levels relatively constant, and decreases gastrointestinal side-effects [1, 8].  After application of a patch, the skin underneath absorbs the drugs and it concentrates in the upper skin levels, gradually diffusing through the skin’s membranes and entering the body [9]. A disadvantage of this system is that only lipophilic, low molecular weight drugs can pass through the skin, but by incorporating enhancers and active energy-dependent methods into the system, dermal anesthesia with hydrophobic substances like lignocaine has been achieved [10].

New molecules with semi-permeable membranes have been developed as carriers that can better target specific tissues and increase absorption rate [1]. Liposomes are nanovesicles that are surrounded by a membrane and are nontoxic, biodegradable, and nonimmunogenic – thus they are promising carriers for drug delivery [11].  However, because of a lot of quality assurance and costs, they have made little strides in clinical practice [12].

Computerized drug delivery systems have been developed inter-disciplinarily, in an attempt to utilize technology to optimize patient care. The advent of these systems, which can be either open-loop or closed-loop, has created a shift towards total intravenous anesthesia [1].  Open-loop systems are known as target-controlled infusion pumps, in which drug concentrations are calculated using a computer and pharmacokinetic models, and the TCI pumps gradually decrease or increase the rate of infusion to meet the desired drug concentration set by an anesthesiologist [1, 13].  Closed-loop systems monitor a patient’s variables such as muscle relaxation, hypnosis, and analgesia in real-time, while a computer-controlled feedback mechanism delivers drugs based on these parameters [14].  This type of computerized system is being developed as a way to provide anesthesia in distant locations, known as tele-anesthesia [15].

References

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