Method needle-free

The use of needle-free jet devices for the delivery of nucleic acids has been described for various disease models, and has been found to generally enhance DNA uptake in various tissues and to increase DNA vaccine efficacy. Jet injection has been found to be an efficient method to induce papillomas in rabbits by inoculation with cottontail rabbit papillomavirus DNA (Brandsma et al., 1991). Jet injection has been used to introduce DNA through the skin surface, effectively transfecting skin, muscle, fat and mammary tumor tissue (Furth et al., 1992). 

Bramson, J., et al. 2003. Enabling topical immunization via microporation A novel method for pain-free and needle-free delivery of adenovirus-based vaccines. Gene Ther 10 251. 

Drug delivery via the nasal route offers a number of advantages, the most important of which is the possibility of needle-free treatment. It also means that—in addition to the newly developed peptide- and protein-based drugs—this method is also suitable for a wide variety and perhaps most of the drugs that are currently in use. However, it is not only convenience that sets nasal drug delivery apart This method also provides a rapid onset of action and high bioavailability. 

Although attempts made so far to prepare complexes of the type Mn (aromatic)2 or [Mn(aromatic) 2] + have been unsuccessful, it has been possible to isolate a bright yellow tetraphenylborate of the [Re(C6He)2] + ion (as fine needles) and a red-brown reineckate of the [Re(sj/TO-(CHs)3 CeHs) 2] ion by the aluminum chloride method. The free bases are stable, but attempts at reduction to the uncharged complex of the element were unsuccessful (5S). 

Selection of the appropriate route of administration and delivery device is critical for the commercial success of a drug product. Although injections are the most efficient delivery method for proteins, they are not always the most suitable from the patient s perspective. Few routes of administration (IV, IM, SC, pulmonary, and topical for local delivery) have been successful to date with protein therapeutics because of the size and complexity of the protein structure. Consideration of the bioavailability via a given route must be made when determining the dose required. Use of a delivery device such as an implantable pump, needle-free injector, or dry-powder inhaler may yield a product with a commercial advantage over a competitor s product. 

Establishing clinical bioequivalence to a reference delivery method, usually a needle and syringe or an autoinjector or pen injector is the customary method of demonstrating that these conditions have been successfully met. This requires that the maximum blood plasma concentration of the drug (Cmax) and the total area under the time-concentration curve (AUC), as well as their associated confidence intervals, adequately approximate a reference product. The standard criteria to establish bioequivalence are 70-143% for Cmax and 80-125% for AUC (Fig. 3 for an example of a bioequivalent needle-free delivery). 

Establishing bioequivalence is less relevant for vaccines and is usually done instead by comparing seroconversion rates in naive recipients to a needle-administered reference group. Several reports (Table 1) actually demonstrate increased seroconversion rates with needle-free delivery (or equivalent seroconversion with much lower doses). This is thought to be due to better targeting of the immune cells in the epidermis and, to a lesser extent, the dermis. This area is not yet fully understood, however, as other reports point to generally equivalent seroconversion rates between the two methods. 

Minimally invasive methods of transdermal drug delivery, e.g., needle-free injections... 

Injection still remains the most common method for administration of proteins and peptides. Efforts are being made to use needle-free or painless injections and also to improve the controlled delivery by parenteral route. 

Laudanosine, C21H27O4N. This alkaloid occurs in the liquor from which thebaine is precipitated, and can be isolated by Hesse s method. The crude alkaloid is purified by extraction with small quantities of ether, in which laudanosine is soluble, and finally by precipitation with potassium iodide. The free base crystallises from hot benzene in needles, m.p. 89°, [ ] f 103-23° (EtOH), is soluble in alcohol, chloroform, hot benzene or... 

Flow-Based Systems Needle-type sensors with a fluid flowing over the sensor tip seem to resist biofouling and extend sensor lifetime.31 There are numerous methods that have been investigated for flow-based sensors, such as microperfusion systems,75 microdialysis,76 77 and ultrafiltration.78 Reduced fouling was found with an open microflow system where slow flow of protein-free fluid over the sensor surface at the implant site is effected.73 Different from the other flow-based sensors, the open microflow is controlled by the subcutaneous tissue hydrostatic pressure and does not require a pump. 

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