Implantable device for drug delivery and blood sampling in the rat

An implantable drug-delivery and venous sampling device is described that is constructed from a polyvinyl chloride catheter and a rubber intravenous catheter plug coated with Silastic. The implant was used for repeated venous sampling and for both administration of parenteral solutions and injections into the right colon of the rat for periods to 1 mo.     

Novel "three-in-one" peptide device for genetic drug delivery

We here describe a new strategy for the delivery of oligonucleotides to cells that is based on the use of a short peptide containing three functional units: a membrane-penetrating segment, a DNA-binding domain and a cell-localization sequence. The designed vector binds strongly to oligonucleotides and has membrane-perturbing abilities in vitro. This type of multi-functional device may be a powerful tool to achieve efficient delivery of genetic drugs in vivo.     

Overcoming physiological barriers by nanoparticles for intravenous drug delivery to the lymph nodes

The lymph nodes are major sites of cancer metastasis and immune activity, and thus represent important clinical targets. Although not as well-studied compared to subcutaneous administration, intravenous drug delivery is advantageous for lymph node delivery as it is commonly practiced in the clinic and has the potential to deliver therapeutics systemically to all lymph nodes. However, rapid clearance by the mononuclear phagocyte system, tight junctions of the blood vascular endothelium, and the collagenous matrix of the interstitium can limit the efficiency of lymph node drug delivery, which has prompted research into the design of nanoparticle-based drug delivery systems. In this mini review, we describe the physiological and biological barriers to lymph node targeting, how they inform nanoparticle design, and discuss the future outlook of lymph node targeting.     

Development of a three-microneedle device for hypodermic drug delivery and clinical application

There is a potential use for intradermic or hypodermic drug delivery in skin surgery or aesthetic surgery. Hypodermic delivery with the use of a noninvasive device can be a more useful, reliable, and effective administration route to obtain higher compliance. The authors developed a microneedle device composed of three fine needles (three-microneedle device). The tip of each needle was fabricated with a bevel angle to release a drug broadly into the tissue in a horizontal fashion. In this study, the authors investigated the usefulness of this newly developed three-microneedle device for hypodermic liquid injection, focusing on the optimum insertion depth and the diffusion of injected materials to the tissue. The authors also assessed the efficacy of and patient satisfaction with three-microneedle device injections of botulinum toxin type A for wrinkle reduction in patients with glabellar rhytides. The three-microneedle device yielded consistent results in hypodermal diffusion. On India ink diffusion test and ultrasonographic imaging, three-microneedle device injection showed a broad diffusion in horizontal extension, as compared with usual 31-gauge needle injection. The efficiency and satisfaction of the patients receiving botulinum toxin type A with the three-microneedle device were highly rated. Three-microneedle device delivery enables accurate and broad diffusion of injected substances, thus reducing the total dose and/or injection number of drugs. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.     

An open-loop insulin delivery device for the control of experimental diabetes.

A new insulin delivery device has been developed and tested. It includes a reservoir, a pump, and a power pack. The reservoir holds 75 ml and is coupled to a precision peristaltic pump whose delivery can be set to any one of 128 different flow rates from 0 to 80 microliter/min (+/- 1.6% over 10 months) using the flow rate controller included in the battery power pack. The system weighs 525 g, consuming 50 mW at the maximum pumping rate, proportionately less at lower rates. Ten pumps have undergone bench tests for 30 days. One has been subjected to an extended life test of 16 months without change of tubing while seven complete systems have been used on dogs to demonstrate their capability for precise long-term (up to 16 months) intravenous insulin therapy. With this system, experimental diabetes has been controlled in 7 dogs for periods now extending beyond 16 months. This device now qualifies for-long term studies on hospitalized patients with diabetes mellitus.     

Nanomaterials for ocular drug delivery

Efficient drug delivery to the eye remains a challenging task for pharmaceutical scientists. Due to the various anatomical barriers and the clearance mechanisms prevailing in the eye, conventional drug delivery systems, such as eye drop solutions, suffer from low bioavailability. More invasive methods, such as intravitreal injections and implants, cause adverse effects in the eye. Recently, an increasing number of scientists have turned to nanomaterial-based drug delivery systems to address the challenges faced by conventional methods. This paper highlights recent applications of various nanomaterials, such as polymeric micelles, hydrogels, liposomes, niosomes, dendrimers, and cyclodextrins as ocular drug delivery systems to enhance the bioavailability of ocular therapeutic agents.     

Nanoparticles for drug delivery to the lungs

The lungs are an attractive route for non-invasive drug delivery with advantages for both systemic and local applications. Incorporating therapeutics with polymeric nanoparticles offers additional degrees of manipulation for delivery systems, providing sustained release and the ability to target specific cells and organs. However, nanoparticle delivery to the lungs has many challenges including formulation instability due to particle-particle interactions and poor delivery efficiency due to exhalation of low-inertia nanoparticles. Thus, novel methods formulating nanoparticles into the form of micron-scale dry powders have been developed. These carrier particles exhibit improved handling and delivery, while releasing nanoparticles upon deposition in the lungs. This review covers the development of nanoparticle formulations for pulmonary delivery as both individual nanoparticles and encapsulated within carrier particles.     

Molecular aptamers for drug delivery

The active targeting of drugs in a cell-, tissue- or disease-specific manner represents a potentially powerful technology with widespread applications in medicine, including the treatment of cancers. Aptamers have properties such as high affinity and specificity for targets, easy chemical synthesis and modification, and rapid tissue penetration. They have become attractive molecules in diagnostics and therapeutics rivaling and, in some cases, surpassing other molecular probes, such as antibodies. In this review, we highlight the recent progress in aptamer-mediated delivery for therapeutics and disease-targeting based on aptamer integration with a variety of nanomaterials, such as gold nanorods, DNA micelles, DNA hydrogels and carbon nanotubes.     

Novel technologies for antiangiogenic drug delivery in the brain

Antiangiogenic therapies aimed at inhibiting the formation of tumor vasculature hold great promise for cancer therapy, with multiple compounds currently undergoing clinical trials. As with many forms of chemotherapy, antiangiogenic drugs face numerous hurdles in their translation to clinical use. Many such promising agents exhibit a short half-life, low solubility, poor bioavailability, and multiple toxic side effects. Furthermore, when targeting malignant brain tumors the blood-brain barrier represents a formidable obstacle, preventing drugs from penetrating into the central nervous system (CNS). In this review, we discuss several pre-clinical antiangiogenic therapies and describe issues related to the unique conditions in the brain with regard to cancer treatment and neurotoxicity. We focus on the limitations of antiangiogenic drugs in the brain, along with numerous solutions that involve novel biomaterials and nanotechnological approaches. We also discuss an example in which modifying the properties of an antiangiogenic compound enhanced its clinical efficacy in treating tumors while simultaneously mitigating undesirable neurological side-effects.     

Novel technologies for antiangiogenic drug delivery in the brain

Antiangiogenic therapies aimed at inhibiting the formation of tumor vasculature hold great promise for cancer therapy, with multiple compounds currently undergoing clinical trials. As with many forms of chemotherapy, antiangiogenic drugs face numerous hurdles in their translation to clinical use. Many such promising agents exhibit a short half-life, low solubility, poor bioavailability and multiple toxic side effects. Furthermore, when targeting malignant brain tumors the blood-brain barrier represents a formidable obstacle, preventing drugs from penetrating into the central nervous system (CNS). In this review, we discuss several preclinical antiangiogenic therapies and describe issues related to the unique conditions in the brain with regard to cancer treatment and neurotoxicity. We focus on the limitations of antiangiogenic drugs in the brain, along with numerous solutions that involve novel biomaterials and nanotechnological approaches. We also discuss an example in which modifying the properties of an antiangiogenic compound enhanced its clinical efficacy in treating tumors while simultaneously mitigating undesirable neurological side-effects.Key words: angiogenesis, CNS, glioma, drug-delivery, brain, blood-brain-barrier, nanoparticles, lodamin     

Small-scale systems for in vivo drug delivery

Recent developments in the application of micro- and nanosystems for drug administration include a diverse range of new materials and methods. New approaches include the on-demand activation of molecular interactions, novel diffusion-controlled delivery devices, nanostructured 'smart' surfaces and materials, and prospects for coupling drug delivery to sensors and implants. Micro- and nanotechnologies are enabling the design of novel methods such as radio-frequency addressing of individual molecules or the suppression of immune response to a release device. Current challenges include the need to balance the small scale of the devices with the quantities of drugs that are clinically necessary, the requirement for more stable sensor platforms, and the development of methods to evaluate these new materials and devices for safety and efficacy.     

Radiation crosslinked polymerization of methacrylamide and psyllium to develop antibiotic drug delivery device

Psyllium is a medicinally important polysaccharide and its modification with methacrylamide through radiation crosslinked polymerization will develop hydrogels meant for drug delivery applications. The present paper deals with the preparation of hydrogels and their characterization by SEMs, FTIR, TGA and swelling studies. The release dynamics of model antibiotic drug rifampicin from the hydrogels has been studied for the evaluation of the release mechanism. The values of the diffusion exponent ‘n’ have been obtained (0.64, 0.58 and 0.57), respectively, in distilled water, pH 2.2 buffer and pH 7.4 buffer. The release of the drug from the hydrogels occurred through non-Fickian diffusion mechanism.     

A diaphragm delivery device for flow microcalorimetry

A diaphragm delivery device is described which allows delivery of a reagent to a flow system at a constant or variable flow rate. The device presents only a Teflon surface to the reagent and avoids direct contact with the pump. This delivery system is used to cireumvent the serious problem of reagent interaction with the working parts of pumps used in flow microcalorimetry while retaining the convenience of switching from one solution to another. The reaction of α-chymotrypsin with the nonspecific substrate 3-(2-furyl)-acryloylimidazole is used to illustrate the advantages of the diaphragm delivery device.