Drug Delivery Letters - Volume 1, Issue 2, 2011

Liquid needle-free injectors employ high-velocity liquid jets to deliver drugs and vaccines. Several parameters are critical to the injection quality: nozzle diameter, volume of drug delivered, ampoule diameter, pressure that drives liquid volume, and impact gap (distance between piston and trigger). A physical model is presented to calculate the stagnation pressure of the injection jet. Two types of the injection systems were tested: a spring-powered system and a voice-coil powered system. The calculation results show that the variation of stagnation pressure with time matches the experimental measurement under the same system conditions. The maximum stagnation pressure determines whether the jet can erode and penetrate into the skin. The maximum stagnation pressure was calculated under three conditions: different volumes, different spring rates and different ampoule diameters, and the results were compared with the experimental measurements. The experiments validated the physical model.

Taxanes (paclitaxel and docetaxel) are among the most active cytotoxic agents in use in oncology, being widely used in adjuvant and advanced treatment settings in multiple tumor types. Due to the impressive benefits offered by the taxanes, different strategies are in development, aimed at reducing their systemic toxicity and the need for premedication, while improving anti-tumor spectra and treatment efficacy. Although a remarkable amount of effort has been aimed at overcoming delivery difficulties, very few compounds have reached clinical trials, and some of those few have failed advanced trials. This mini-review reports the most recent developments in advanced taxane delivery approaches, with particular focus on receptor-targeted delivery systems.

Short interfering RNAs, or siRNAs, belong to a class of RNA species which play a role in both cellular defence and gene regulation. siRNAs are members of a larger RNA interference pathway found within cells and are involved in the degradation of RNAs which possess complementarity to specific target sequences. This property has given siRNA technology the potential to become a powerful new tool for a wide variety of disciplines, ranging from the design of novel anti-cancer agents to agricultural applications. The following review outlines novel delivery systems that can be used for applied siRNA technologies. Improved delivery systems for the cellular uptake of siRNAs using both viral expression vectors and nanoliposomal particles are discussed. New therapeutics that can be used to combat human disease and agricultural applications of siRNA technologies are also described. This review attempts to pave the way for future innovations based upon RNA interference in medicine and agriculture.

Growing demands on a suitable formulation method that ensures the stability of the active compound coupled with the limitations of current methods (milling, lyophilization, spray drying, and freeze spray drying) has brought wide attention to supercritical fluid (SCF) technology. Advantages of using the SCF technology comprise its high abilities, adaptability in providing alternative processing methods, high compressibility and diffusivity of the supercritical fluid, capability as an alternative for conventional organic solvents, and the option to attain different processing parameters which would be otherwise difficult to conduct with traditional methods. This review proposes to present an up-to-date outlook on dry powder pulmonary formulations of macromolecules using SCF technology.

Polymers that exhibit physicochemical responses to stimuli have been widely explored as potential drug delivery systems. Different kind of stimuli investigated to date includes, for example, chemical substances and changes in temperature, pH and electric fields. Polymers that exhibit dramatic changes in their behavior in an aqueous solution at temperatures close to the body temperature are of particular interest in drug delivery and biomedical applications. Thermosensitive polymers have a wide range of applications, specially, the thermosensitive triblock copolymers because they exhibit unique aqueous solution properties, biodegradability and biocompatibility. These copolymers can be designed to be used as potential drug delivery systems for therapeutic protein drugs or poorly water soluble drugs. This article reviews the applications of polymer solutions with the ability to form in situ implants under temperature changes, in areas of interest to biomedical, pharmacist and engineer scientists. Recent advantages on thermosensitive and biodegradable polymers are discussed to give a wide overview of the available strategies to modify them in order to make them suitable for potential applications in health products.

Capuramycin (CM) antibiotics are bactericidal for Mycobacterium tuberculosis (MTB) in vitro. Due to their low membrane permeability and efflux, however, these compounds are less effective against intracellular MTB. To improve intracellular activity, we created phospholipid Phosal 53 MCT-based nanoemulsion (NE) formulations of CM analogues SQ641, SQ641-aua, SQ641-2aua and SQ997-3aua. We assessed intracellular killing activity of the 4 CM analogues and their NE formulations against MTB using the J774A.1 mouse macrophage cell line. Of the several emulsifiers investigated, d-tocopheryl polyethylene glycol 1000 succinate (TPGS) produced the most efficacious and stable emulsion, with a mean particle size below 70 nm. CM analogue-NE formulations prepared using TPGS as emulsifier (-NETPGS) showed significantly improved intracellular activity over free drugs. The order of intracellular activity was SQ641-2aua- NETPGS>SQ997-3aua-NETPGS>SQ641-aua-NETPGS>SQ641-NETPGS. At 2× MIC the intracellular killing activity of SQ641- 2aua-NETPGS, the most active formulation, surpassed that of first-line anti-TB drugs isoniazid (INH), rifampin (RIF) and ethambutol (EMB). Enhanced intracellular activity of the -NETPGS formulation, perhaps, was due to TPGS mediated blocking of the drug efflux.

The use of nanoemulsions as a carrier system for skin targeting has attracted increased attention over recent years. Nanoemulsions can be intended for both topical and systemic delivery of the biologically active agents for controlled and targeted delivery. Nanoemulsion droplets fall within the size range of 20-200nm, typically below 100nm. Nanoemulsions have high surface area and ability to solubilize poorly soluble drugs. They are reported to have higher skin permeation and retention potential than other novel drug delivery systems like nanoparticles, liposomes, microemulsions etc. Use of nanoemulsions for skin targeting of drug is a current research scenario in the field of Pharmaceutics. This research area has generated immense interest from the Pharmaceutical industry and a number of nanoemulsion based cosmetics formulations like anti-aging creams, skin cleansing lotions etc. are available in the market. Recently, Zydus Cadilla launched the Oxalgin NanoGel™ diclofenac sodium nanoemulsion gel showing the importance of nanoemulsion as carrier system for skin targeting of drugs. This review embodies an in-depth discussion on composition, application, its mechanism of skin permeation and commercial aspects of nanoemulsions for skin targeting.

The respiratory system is in extensive contact with the outside environment, being a place for materials and chemical exchanges. Lungs and airways are constantly exposed to hazardous conditions, and thus able to develop various diseases. Pulmonary administration of compounds for the treatment of respiratory tract diseases has been performed since ancient cultures, and is currently being studied as a route of administration of drugs for systemic action. On the other hand, parenteral administration of drugs to treat lung disorders is also being explored. In order to circumvent the disadvantages presented by conventional formulations, nanotechnology-based drug delivery systems for pulmonary administration and pulmonary targeting have been exploited. In this field, polymeric micelles are emerging as a promising platform for drug delivery, cancer targeting and tumor imaging applications. This paper is a literature revision regarding the use of polymeric micelles as drug delivery systems for pulmonary administration of drugs as well as for systemic targeted treatment of lung diseases.