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Maggio E.T.,Aegis USA | Pillion D.J.,University of Alabama at Birmingham
Drug Delivery and Translational Research | Year: 2013

A new class of alkylsaccharide transmucosal delivery enhancement agents are described that overcome the principal limitations preventing broad acceptance of intranasal administration for many potential applications in systemic drug delivery, namely, poor transmucosal absorption and damage to the nasal mucosa. This review will describe recent developments in use of these excipients in human clinical trials and preclinical studies along with their chemical and pharmacological properties and explore commercial implications of the use of these excipients in introduction of new intranasal formulations of peptidic and nonpeptidic drugs. © 2012 Controlled Release Society.


Polysorbates and other polyoxyethylene-based surfactants are incorporated into most biotherapeutics to prevent protein aggregation in order to minimize loss of efficacy, induction of unwanted immunogenicity, altered pharmacokinetics and reduced shelf life. While they are effective in initially preventing protein aggregation, they contain ether linkages (within polyoxyethylene moieties) and in the case of polysorbate 80 unsaturated alkyl chains that spontaneously and rapidly auto-oxidize in aqueous solution to protein-damaging peroxides, epoxy acids and reactive aldehydes, including formaldehyde and acetaldehyde. Oxidative damage induces unwanted immunogenicity and in some instances promotes re-aggregation. Immunogenicity of biotherapeutics is a serious and growing concern for the US FDA and European Medicines Agency and will have significant and growing impact on the development and regulatory approval of both biosimilar and new innovator biotherapeutics. © 2013 Future Science Ltd.


Argyropoulos C.,University of Texas at Austin | Chen P.-Y.,University of Texas at Austin | D'Aguanno G.,Aegis USA | Engheta N.,University of Pennsylvania | Alu A.,University of Texas at Austin
Physical Review B - Condensed Matter and Materials Physics | Year: 2012

The anomalous transmission properties of zero-permittivity ultranarrow channels are used to boost Kerr nonlinearities and achieve switching and bistable response for moderate optical intensities. Strong field enhancement, uniform all along the channel, is a typical feature of ε-near-zero supercoupling and is shown to be particularly suited to enhance nonlinear effects. This is obtained by designing narrow apertures at cutoff in a plasmonic screen. We show that this nonlinear mechanism can significantly outperform nonlinearities in traditional Fabry-Pérot resonant gratings. © 2012 American Physical Society.


The most effective option for the medical treatment of patients with acromegaly is the use of somatostatin analogs. Octreotide acetate is a synthetic analog of somatostatin, with similar effects but a prolonged duration of action. Octreotide acetate is routinely given by subcutaneous (s.c.) or intramuscular injection. In the present study, we examined the feasibility of oral delivery of octreotide acetate reconstituted with increasing concentrations (0.5%, 1.5% and 3.0%) of Intravail®, a patented alkylsaccharide transmucosal absorption enhancing agent. The pharmacokinetics of orally delivered (by gavage) octreotide acetate in Intravail® were compared to those of octreotide acetate administered subcutaneously in sodium acetate buffer to male Swiss Webster mice. Oral delivery of octreotide acetate in 0.5% Intravail® significantly enhanced total uptake (1254.08. ng/ml/min vs. 311.63. ng/ml/min, respectively), serum half-life (52.1. min vs. 1.3. min, respectively), and relative bioavailability (4.0 vs. 1.0, respectively) when compared to delivery by s.c. injection. Higher concentrations of Intravail® did not further enhance uptake, serum half-life, or bioavailability. The results of this study indicate that oral delivery of octreotide acetate in Intravail® is feasible, and is an effective method of administration which significantly improves uptake, bioavailability and half-life when compared to s.c. injection. Thus, oral delivery of octreotide acetate in Intravail® may have significant potential as a novel, non-invasive approach to the treatment of acromegaly and octreotide-mediated symptoms of carcinoid and VIP-secreting tumors. © 2011 Elsevier B.V.


Alu A.,University of Texas at Austin | D'Aguanno G.,Aegis USA | D'Aguanno G.,U.S. Army | Mattiucci N.,Aegis USA | And 2 more authors.
Physical Review Letters | Year: 2011

Extraordinary optical transmission through metallic gratings is a well established effect based on the collective resonance of corrugated screens. Being based on plasmonic resonances, its bandwidth is inherently narrow, in particular, for thick screens and narrow apertures. We introduce here a different mechanism to achieve total transmission through an otherwise opaque screen, based on an ultrabroadband tunneling that can span from dc to the visible range at a given incidence angle. This phenomenon effectively represents the equivalent of Brewster transmission for plasmonic and opaque screens. © 2011 American Physical Society.


Argyropoulos C.,University of Texas at Austin | Chen P.-Y.,University of Texas at Austin | Monticone F.,University of Texas at Austin | D'Aguanno G.,Aegis USA | Alu A.,University of Texas at Austin
Physical Review Letters | Year: 2012

Here we extend the reach of Fano resonant coupling by combining this concept with cloaking and plasmonic resonances in a single nonlinear nanoparticle, in order to realize giant all-optical scattering nanoswitches controlled by moderate pumping intensities. We show that a core-shell nonlinear plasmonic particle may be designed to abruptly switch from being completely cloaked to being strongly resonant, with up to a 40 dB cross-sectional difference. Self-tunable optical cloaks and resonant scatterers are envisioned for use as efficient all-optical switches and nanomemories. © 2012 American Physical Society.


Mattiucci N.,Aegis USA | D'Aguanno G.,Aegis USA | Bloemer M.J.,Charles M Bowden Laboratory
Optics Letters | Year: 2012

We exploit the properties of ultranarrow, Fano-like resonances generated by the coupling of long range surface plasmons with ultrathin (∼10 nm), metallic, subwavelength gratings embedded in a nonlinear, cubic material to obtain all-optical switching at telecommunication wavelengths for extremely low input power. We provide an example of a silver metallic grating embedded in a chalcogenide glass (As2S3), and we show the concrete possibility to achieve all-optical switching at local field intensities compatible with the photo-darkening threshold of the material. © 2012 Optical Society of America.


De Ceglia D.,Aegis USA | Vincenti M.A.,Aegis USA | Scalora M.,Charles wden Research Center
Optics Letters | Year: 2012

We demonstrate controllable light deflection in thick metal gratings with periodic subwavelength slits filled with an active material. Under specific illumination conditions, the grating becomes nearly transparent and acts as a uniform optical phased-array antenna where the phase of the radiating elements is controlled by modifying the index of refraction of the material that fills each slit. The beam-steering operational regime occurs in a wide wavelength band, and it is relatively insensitive to the input angle. © 2012 Optical Society of America.


Maggio E.T.,Aegis USA
Journal of Excipients and Food Chemicals | Year: 2012

Aggregation can have a number of deleterious effects on biotherapeutics including the loss of efficacy, the induction of unwanted immunogenicity, altered pharmacokinetics, and reduced shelf life. Aggregation is ameliorated by the inclusion of surfactants in biotherapeutics formulations, typically non-ionic polymeric ether surfactants. The most commonly used examples are Tween® 20 (Polysorbate 20) and Tween® 80 (Polysorbate 80). Others include Triton™ X-100, Pluronic® F-68, Pluronic® F-88, Pluronic® F-127 (poloxamers), and Brij 35 (polyoxyethylene alkyl ether). The usefulness of polysorbates, in particular in preventing protein aggregation in biotherapeutic formulations, is well accepted. However, polysorbates contain ether linkages and unsaturated alkyl chains that have been shown to auto-oxidize in aqueous solution to protein-damaging peroxides and reactive aldehydes including formaldehyde and acetaldehyde. The peroxides principally affect methionine and tryptophan moieties. The aldehydes react with primary amino groups on proteins and are known to induce immunogenicity of proteins in the absence of aggregation or adjuvants. Detection of protein aggregation and prevention of aggregation using polysorbates is relatively straightforward using light scattering or size exclusion chromatography methods. Detection of oxidative damage to amino acyl moieties or increased immunogenicity resulting from the reaction of biotherapeutics with the degradation products of polysorbates is considerably more difficult and has generally been ignored in the scientific literature. As an increasing number of biotherapeutic agents come into use in common clinical practice, including both as innovator and as biosimilar products, these latter issues will come under increased scrutiny. Substitution of non-ionic, non-ether-based surfactants, could offer significant improvements in stability, reduced immunogenicity, and shelf life, and represents a significant unmet need in the field of biotherapeutics formulation. © IPEC-Americas Inc.


Maggio E.T.,Aegis USA
Journal of Excipients and Food Chemicals | Year: 2014

Intranasal drug delivery is becoming an increasingly important form of drug administration for chronic and chronic-intermittent diseases. Important new applications currently in development include drugs for diabetes, osteoporosis, obesity, certain types of convulsive disorders, migraine headaches, symptomatic pain relief, nausea, and anxiety, among others. Transmucosal absorption across the nasal mucosa is generally limited to molecules less than 1,000 Da. Systemic delivery of larger molecules requires formulations with a suitable transmucosal absorption enhancer. More than one hundred potential transmucosal absorption enhancing excipients have been tested to date. Nearly all have failed due to poor effectiveness or unacceptable toxicity to the mucosal tissue. Alkylsaccharides, cyclodextrins, and chitosans have emerged as leading candidates for potential broad clinical applications allowing the development of convenient, patient-friendly, needle free formulations of small molecule drugs, as well as, peptide and protein drugs that can be administered at home, at work, or in other public and private settings outside of the doctor's office or hospital environment. © IPEC-Americas Inc.

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