**4. Future considerations**

for treating neurological disorders. The drugs may be administered directly into the CNS or administered systematically for targeted action in the CNS. The osmotic and chemical opening of the blood-brain barrier as well as the transport/carrier systems constitutes some of the widely reported strategies to promote the permeation of blood-brain barrier (BBB) and delivery of drugs in brain. In conjunction with the net delivery of drug, the access to the intended target site within the CNS is also important. To serve this purpose, the drugs may be conjugated with various nanostructures such as liposomes and NPs and a suitable route of administration can be sought. It has been postulated that nanoscale drug carriers possess a great potential for improving the delivery of drugs through nasal routes to deliver drugs to the brain. Among other mucosal sites, nasal delivery is especially attractive for brain-targeted drug delivery, as the nasal epithelium is characterized by its relatively high permeability, vuscularized mucosa, and low enzymatic activity. If a nasal drug formulation is delivered deep and high enough into the nasal cavity, the olfactory mucosa may be reached and drug transport into the brain and/or

Transdermal systems in the form of patches deliver the drugs across the skin barrier for systemic effects at a predetermined and controlled rate. Due to concentration gradient between the transdermal patch and blood, the drug will continue diffusing into the blood for prolonged period of time and maintain constant drug concentration in the blood flow. Transdermal drug delivery avoids problems such as gastrointestinal irritation, metabolism, pH-dependent variation in delivery rate, and interference with gastric emptying due to presence of food. However, slow penetration rates, lack of dosage flexibility and/or precision, and a restriction to relatively low dosage drugs are the major limitations. The stratum corneum of the skin forms a formidable barrier against uptake, and thus transdermal delivery is difficult to achieve. The substances having molecular weight greater than 500 Da [33] and hydrophilic characteristics encounter the difficulty in absorption through skin. Penetration enhancers often have to be added to the delivery system to improve delivery into or through the skin. Recently, it has been demonstrated that atmospheric-pressure argon microplasma irradiation (AAMI) can improve skin permeability of drugs without the need of injection needles and skin damages [34]. AAMI can be a promising alternative to promote drug delivery through the skin and simultaneously minimize the pain from other manipulations related to skin penetration enhancement. However, the feasibility of atmospheric microplasma irradiation is

cerebrospinal fluid (CSF) via the olfactory receptor neurons may occur [32].

8 Advanced Technology for Delivering Therapeutics

still under investigation for enhancing percutaneous absorption of drugs.

The delivery of drug to a specific target in the body is comparable to the magic bullet principle applied in nuclear medicine. Nuclear medicine may advance drug development by visualizing biodistribution and site of action [35]. The biodistribution and release kinetics of drug from the novel formulations can be quantified by radiolabeling with γ-emitting radionuclide. Many nuclear medicine departments have participated in the assessment of drug performance and toxicity in contributing data to clinical trials. The application of nuclear medicine techniques to the evaluation of pharmaceutical formulations has been an interesting area of work. Scintigraphy can be used to determine the position of drug release and assess site-specific absorption of orally administered drugs, for example, the evaluation of controlled release formulation designed to release the drug specifically in colon [36]. Hence, the importance of nuclear medicine in drug delivery application has been described in detail in this book.

The new delivery methods could enhance the performance of drugs by increasing effectiveness, safety, and patient compliance and ultimately reduce healthcare costs. Nanotechnology could be strategically implemented in developing new drug delivery systems that can expand drug markets. Nanomaterials are poised to take advantage of existing cellular machinery to facilitate the delivery of drugs. However, clinical development of drugs is halted because of poor biopharmaceutical and undesirable pharmacokinetic properties. Novel delivery technologies are being tested for overcoming the barriers toward safe delivery of drugs. An in-depth understanding of novel strategies constitutes the primary focus and subsequent demonstration of easy scale-up of the formulations with favorable pharmacokinetics and toxicity profiles could augment the translation of research findings into practical therapeutics. A collaborative effort among scientists in various disciplines, including medicine, materials science, engineering, physics, and biotechnology could potentiate the translation of novel laboratory innovation into commercially viable medical products.
