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Advanced Drug Delivery Reviews (v.61, #15)
Micro- and nanotechnologies for intelligent and responsive biomaterial-based medical systems
by Mary Caldorera-Moore; Nicholas A. Peppas (pp. 1391-1401).
Advances in medical treatments of a wide variety of pathophysiological conditions require the development of better therapeutic agents, as well as a combination of the required therapeutic agents with device-integrated biomaterials that can serve as sensors and carriers. Combination of micro- and nano-fabricated systems with intelligent biomaterials that have the ability to sense and respond is a promising avenue for the development of better diagnostic and therapeutic medical systems. Micro- and nano-electromechanical systems (MEMs and NEMs) are now becoming a family of potentially powerful new technologies for drug delivery, diagnostic tools, and tissue engineering. Improvements in micro- and nano-fabrication technologies have enhanced the ability to create better performing therapeutic systems for numerous pathophysiological applications. More importantly, MEMS- and NEMS-based tissue regeneration scaffolds, biosensors, and drug delivery devices provide new opportunities to mimic the natural intelligence and response of biological systems.
Keywords: Responsive hydrogels; Intelligent therapeutics; Micro- and nano-electromechanical systems; Biosensors; Controlled drug delivery; Tissue engineering
Molecular and magnetic resonance imaging: The value of immunoliposomes
by Dorota Kozlowska; Paul Foran; Peter MacMahon; Martin J. Shelly; Stephen Eustace; Richard O'Kennedy (pp. 1402-1411).
Molecular imaging has the potential to transform the field of diagnostic imaging through enabling far more detailed investigation and characterisation of disease processes than is currently possible. Magnetic resonance imaging (MRI) is capable of three-dimensional non-invasive imaging of opaque tissues at near cellular resolution. Among the imaging techniques available today, MRI has, perhaps, the greatest potential to exploit the possibilities that molecular imaging presents. Nanoparticles are the focus of intense research, due to a wide variety of potential applications in the biomedical, optical, and electronic fields. In this article we examine the progress made in the development of nanoparticles as targeted contrast agents for molecular magnetic resonance imaging. In particular, we will examine the potential of antibody-targeted liposomes (immunoliposomes) as vehicles for delivering MRI contrast agents to cellular biomarkers, thus enabling visualisation of structures and processes at the molecular level. We will address some of the challenges that must be faced by researchers in this field before the progress made in the laboratory can be translated into improved clinical diagnostics and therapeutics.
Keywords: Abbreviations; Ab; antibody; DCC; N,N′-dicyclohexylcarbodiimide; DSPC; 1,2-distearoyl-; sn; -glycero-3-phosphocholine; EPR; enhanced permeability and retention; Fab′; antibody fragment; Gd–BSA; diethylenetriaminepentaacetic acid α,ω-bis(8-stearoylamido-3,6-dioxaoctylamide) gadolinium salt; Gd–DTPA; gadolinium–diethylenetriaminepentaacetic acid; Her2; human epidermal growth factor receptor 2, also known as HER2/neu, ErbB-2 or ERBB2; HPMA; N-(2-hydroxypropyl)methacrylamide; kDa; kilodaltons; mAb; monoclonal antibody; MR; magnetic resonance; MRI; magnetic resonance imaging; MPS; mononuclear phagocyte system; NGPE; N-glutaryl-phosphatidylethanolanime; PAP; polychelating amphiphilic polymer; PE; phosphatidylethanolamine; PEG; polyethylene glycol; PEG–DSPE; polyethylene glycol 1, 2-distearoyl-sn-glycero-3-phosphatidylethanolamine; PET; positron emission tomography; RES; reticuloendothelial system; R; 1; longitudinal relaxation rate; R; 2; transverse relaxation rate; r; 1; longitudinal relaxivity; r; 2; transverse relaxivity; scFv; single chain variable fragment (of an antibody); SATA; succinimidyl-S-acetyl thioacetate; SPDP; N-succinimidyl-pyridyl-dithiopropionate; SPECT; single photon emission computed tomography; T; 1; longitudinal relaxation time; T; 2; transverse relaxation time; w/v; weight per volumeMolecular imaging; Magnetic resonance imaging; Immunoliposomes; Targeted nanoparticles; Contrast agents; Gadolinium
Squalene: A natural triterpene for use in disease management and therapy
by L. Harivardhan Reddy; Patrick Couvreur (pp. 1412-1426).
Squalene is a natural lipid belonging to the terpenoid family and a precursor of cholesterol biosynthesis. It is synthesized in humans and also in a wide array of organisms and substances, from sharks to olives and even bran, among others. Because of its significant dietary benefits, biocompatibility, inertness, and other advantageous properties, squalene is extensively used as an excipient in pharmaceutical formulations for disease management and therapy. In addition, squalene acts as a protective agent and has been shown to decrease chemotherapy-induced side-effects. Moreover, squalene alone exhibits chemopreventive activity. Although it is a weak inhibitor of tumor cell proliferation, it contributes either directly or indirectly to the treatment of cancer due to its potentiation effect. In addition, squalene enhances the immune response to various associated antigens, and it is therefore being investigated for vaccine delivery applications. Since this triterpene is well absorbed orally, it has been used to improve the oral delivery of therapeutic molecules. All of these qualities have rendered squalene a potentially interesting excipient for pharmaceutical applications, especially for the delivery of vaccines, drugs, genes, and other biological substances. This paper is the first review of its kind and offers greater insight into squalene's direct or indirect contribution to disease management and therapy.
Keywords: Squalene; Adjuvant; Vaccine; Cancer; Drug carrier; Gene delivery; Antioxidant; Chemopreventive agent; Terpenoid; Terpene
Safety and efficacy of sodium caprate in promoting oral drug absorption: from in vitro to the clinic
by Sam Maher; Thomas W. Leonard; Jette Jacobsen; David J. Brayden (pp. 1427-1449).
A major challenge in oral drug delivery is the development of novel dosage forms to promote absorption of poorly permeable drugs across the intestinal epithelium. To date, no absorption promoter has been approved in a formulation specifically designed for oral delivery of Class III molecules. Promoters that are designated safe for human consumption have been licensed for use in a recently approved buccal insulin spray delivery system and also for many years as part of an ampicillin rectal suppository. Unlike buccal and rectal delivery, oral formulations containing absorption promoters have the additional technical hurdle whereby the promoter and payload must be co-released in high concentrations at the small intestinal epithelium in order to generate significant but rapidly reversible increases in permeability. An advanced promoter in the clinic is the medium chain fatty acid (MCFA), sodium caprate (C10), a compound already approved as a food additive. We discuss how it has evolved to a matrix tablet format suitable for administration to humans under the headings of mechanism of action at the cellular and tissue level as well as in vitro and in vivo efficacy and safety studies. In specific clinical examples, we review how C10-based formulations are being tested for oral delivery of bisphosphonates using Gastro Intestinal Permeation Enhancement Technology, GIPET® (Merrion Pharmaceuticals, Ireland) and in a related solid dose format for antisense oligonucleotides (ISIS Pharmaceuticals, USA).
Keywords: Oral drug delivery; Sodium caprate (C; 10; ); Absorption promoter; Drug delivery platforms; Clinical trials; Oral formulation; Drug delivery systems
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