Electrospun nanofibrous polymeric scaffold with targeted drug release profiles for potential application as wound dressing

The use of high-throughput screening and similar techniques in drug discovery has put a number of evolutionary pressures on drug candidates such that over time there is a tendency for them to increase in molecular weight, increase in log K(octanol/water) and decrease in water solubility. These trends provide an ever-increasing series of challenges for the drug formulator to generate effective, orally bioavailable dosage forms. An important tool in this regard is the use of cyclodextrins, especially chemically modified cyclodextrins. These starch derivatives interact via dynamic complex formation and other mechanisms in a way that camouflages undesirable physicochemical properties, including low aqueous solubility, poor dissolution rate and limited drug stability. Through these effects, cyclodextrins and their derivatives have become popular modalities for increasing oral bioavailability and absorption rate. These actions have positioned cyclodextrins as important enabling and functional excipients. This review aims to assess the use of cyclodextrins in oral and other administration routes in the context of the Biopharmaceutical Classification Systems (BCS), a US FDA-based characterization approach that bins drugs based on solubility and permeability features. Specifically, a framework based on Fickian theory as well as the Noyes-Whiney relationship is constructed to assess where cyclodextrins are likely to be useful and where their use is probably not justified. This working model is examined in the context of a number of published examples in which cyclodextrins have been applied to class I, II, III, and IV drugs and drug candidates.

/pdf/role-of-cyclodextrins-in-improving-oral-drug-delivery-6r3gk8oy0n.pdf

Role of cyclodextrins in improving oral drug delivery

Processing of Polymer Nanofibers Through Electrospinning as Drug Delivery Systems

Nanomedicine in the diagnosis and therapy of neurodegenerative disorders

Tissue engineering of fibrous tissues of the musculoskeletal system represents a considerable challenge because of the complex architecture and mechanical properties of the component structures Natural healing processes in these dense tissues are limited as a result of the mechanically challenging environment of the damaged tissue and the hypocellularity and avascular nature of the extracellular matrix When healing does occur, the ordered structure of the native tissue is replaced with a disorganized fibrous scar with inferior mechanical properties, engendering sites that are prone to re-injury To address the engineering of such tissues, we and others have adopted a structurally motivated approach based on organized nanofibrous assemblies These scaffolds are composed of ultrafine polymeric fibers that can be fabricated in such a way to recreate the structural anisotropy typical of fiber-reinforced tissues This straight-and-narrow topography not only provides tailored mechanical properties, but also serves as a 3D biomimetic micropattern for directed tissue formation This review describes the underlying technology of nanofiber production and focuses specifically on the mechanical evaluation and theoretical modeling of these structures as it relates to native tissue structure and function Applying the same mechanical framework for understanding native and engineered fiber-reinforced tissues provides a functional method for evaluating the utility and maturation of these unique engineered constructs We further describe several case examples where these principles have been put to test, and discuss the remaining challenges and opportunities in forwarding this technology toward clinical implementation

https://www.seas.upenn.edu/~burdick2/papers/2009/Mauck_Tissue%20Engineering%20Part%20B%20-%20Reviews_2009.PDF

Engineering on the straight and narrow: the mechanics of nanofibrous assemblies for fiber-reinforced tissue regeneration.

Electrostatic spinning was applied to the preparation of drug-laden nanofiber for potential use in oral and topical drug delivery. While this technique is in its infancy with regard to pharmaceutical applications, a number of recent publications suggest that it may be of high value in the formulation of poorly water-soluble drugs by combining nanotechnology and solid solution/dispersion methodologies. The purpose of this article is to describe some of these recently published applications. For immediate release oral application, a water-soluble cellulose polymer was selected (i.e., hydroxypropylmethylcellulose, HPMC) while for topical application, a nonbiodegradable, water-insoluble polymer was investigated (i.e., a segmented polyurethane, SPU). Solutions of the polymer and the drugs in appropriate solvents could be spun across various potentials (16-24 kV) generating nanofibers with diameters ranging from 300 to 2000 nm. Dissolution studies found that the non-woven fabrics derived from HPMC and containing itraconazole dissolved over a time course of minutes to hours depending on the formulation used as well as the drug/polymer ratios. Drug release from the SPU samples was dependent on the incorporated drug as well as nanostructure obtained.

The use of polymer-based electrospun nanofibers containing amorphous drug dispersions for the delivery of poorly water-soluble pharmaceuticals

Dendrimeric poly(propylene-imines) as effective delivery agents for DNAzymes: toxicity, in vitro transfection and in vivo delivery.

Dendrimeric poly(propylene-imines) as effective delivery agents for DNAzymes: dendrimer synthesis, stability and oligonucleotide complexation.

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The use of polymer-based electrospun nanofibers containing amorphous drug dispersions for the delivery of poorly water-soluble pharmaceuticals

Dendrimeric poly(propylene-imines) as effective delivery agents for DNAzymes: toxicity, in vitro transfection and in vivo delivery.

Dendrimeric poly(propylene-imines) as effective delivery agents for DNAzymes: dendrimer synthesis, stability and oligonucleotide complexation.