Jonah A. Kaplan

The Self‐Assembly of Anticancer Camptothecin–Dipeptide Nanotubes: A Minimalistic and High Drug Loading Approach to Increased Efficacy

20-(S)-Camptothecin (CPT)-conjugated dipeptides are reported that preassemble into nanotubes with diameters ranging from 80-120 nm. These nanoassemblies maintain a high (∼47 %) drug loading and exhibit greater drug stability (i.e., resistance to lactone hydrolysis), and consequently greater efficacy against several human cancer cells (HT-29, A549, H460, and H23) in vitro compared with the clinically used prodrug irinotecan. A key and defining feature of this system is the use of the CPT-conjugated dipeptide as both the drug and precursor to the nanostructured carrier, which simplifies the overall fabrication process.

Photo-crosslinking of a self-assembled coumarin-dipeptide hydrogel

The self-assembly and photo-crosslinking of a lysine dipeptide functionalized with 7-(diethylamino)-3-coumarin carboxylic acid (7-DAC) is described. Self-assembly of the dipeptide in water and PBS produces a hydrogel comprised of uniform, micrometer length nanofibers. Irradiation of the nanofibers at 365 nm induces dimerization of the coumarin groups, which crosslinks and stabilizes the noncovalent nanofibers and enhances the mechanical properties.

Stretch-Induced Drug Delivery from Superhydrophobic Polymer Composites: Use of Crack Propagation Failure Modes for Controlling Release Rates

The concept of using crack propagation in polymeric materials to control drug release and its first demonstration are reported. The composite drug delivery system consists of highly-textured superhydrophobic electrosprayed microparticle coatings, composed of biodegradable and biocompatible polymers poly(caprolactone) and poly(glycerol monostearate carbonate-co-caprolactone), and a cellulose/polyester core. The release of entrapped agents is controlled by the magnitude of applied strain, resulting in a graded response from water infiltration through the propagating patterned cracks in the coating. Strain-dependent delivery of the anticancer agents cisplatin and 7-ethyl-10-hydroxycamptothecin to esophageal cancer cells (OE33) in vitro is observed. Finally the device is integrated with an esophageal stent to demonstrate delivery of fluorescein diacetate, using applied tension, to an ex vivo esophagus.

Mechanoresponsive materials for drug delivery: Harnessing forces for controlled release ☆

ABSTRACT Mechanically‐activated delivery systems harness existing physiological and/or externally‐applied forces to provide spatiotemporal control over the release of active agents. Current strategies to deliver therapeutic proteins and drugs use three types of mechanical stimuli: compression, tension, and shear. Based on the intended application, each stimulus requires specific material selection, in terms of substrate composition and size (e.g., macrostructured materials and nanomaterials), for optimal in vitro and in vivo performance. For example, compressive systems typically utilize hydrogels or elastomeric substrates that respond to and withstand cyclic compressive loading, whereas, tension‐responsive systems use composites to compartmentalize payloads. Finally, shear‐activated systems are based on nanoassemblies or microaggregates that respond to physiological or externally‐applied shear stresses. In order to provide a comprehensive assessment of current research on mechanoresponsive drug delivery, the mechanical stimuli intrinsically present in the human body are first discussed, along with the mechanical forces typically applied during medical device interventions, followed by in‐depth descriptions of compression, tension, and shear‐mediated drug delivery devices. We conclude by summarizing the progress of current research aimed at integrating mechanoresponsive elements within these devices, identifying additional clinical opportunities for mechanically‐activated systems, and discussing future prospects. Graphical abstract Figure. No Caption available.

Imparting superhydrophobicity to biodegradable poly(lactide-co-glycolide) electrospun meshes.

The synthesis of a family of new poly(lactic acid-co-glycerol monostearate) (PLA–PGC18) copolymers and their use as biodegradable polymer dopants is reported to enhance the hydrophobicity of poly(lactic acid-co-glycolic acid) (PLGA) nonwoven meshes. Solutions of PLGA are doped with PLA–PGC18 and electrospun to form meshes with micrometer-sized fibers. Fiber diameter, percent doping, and copolymer composition influence the nonwetting nature of the meshes and alter their mechanical (tensile) properties. Contact angles as high as 160° are obtained with 30% polymer dopant. Lastly, these meshes are nontoxic, as determined by an NIH/3T3 cell biocompatibility assay, and displayed a minimal foreign body response when implanted in mice. In summary, a general method for constructing biodegradable fibrous meshes with tunable hydrophobicity is described for use in tissue engineering and drug delivery applications.

Fabricating Superhydrophobic Polymeric Materials for Biomedical Applications.

Superhydrophobic materials, with surfaces possessing permanent or metastable non-wetted states, are of interest for a number of biomedical and industrial applications. Here we describe how electrospinning or electrospraying a polymer mixture containing a biodegradable, biocompatible aliphatic polyester (e.g., polycaprolactone and poly(lactide-co-glycolide)), as the major component, doped with a hydrophobic copolymer composed of the polyester and a stearate-modified poly(glycerol carbonate) affords a superhydrophobic biomaterial. The fabrication techniques of electrospinning or electrospraying provide the enhanced surface roughness and porosity on and within the fibers or the particles, respectively. The use of a low surface energy copolymer dopant that blends with the polyester and can be stably electrospun or electrosprayed affords these superhydrophobic materials. Important parameters such as fiber size, copolymer dopant composition and/or concentration, and their effects on wettability are discussed. This combination of polymer chemistry and process engineering affords a versatile approach to develop application-specific materials using scalable techniques, which are likely generalizable to a wider class of polymers for a variety of applications.

Stereotactic core needle breast biopsy marker migration: An analysis of factors contributing to immediate marker migration

ObjectivesTo evaluate breast biopsy marker migration in stereotactic core needle biopsy procedures and identify contributing factors.MethodsThis retrospective study analyzed 268 stereotactic biopsy markers placed in 263 consecutive patients undergoing stereotactic biopsies using 9G vacuum-assisted devices from August 2010-July 2013. Mammograms were reviewed and factors contributing to marker migration were evaluated. Basic descriptive statistics were calculated and comparisons were performed based on radiographically-confirmed marker migration.ResultsOf the 268 placed stereotactic biopsy markers, 35 (13.1%) migrated ≥1 cm from their biopsy cavity. Range: 1–6 cm; mean (± SD): 2.35 ± 1.22 cm. Of the 35 migrated biopsy markers, 9 (25.7%) migrated ≥3.5 cm. Patient age, biopsy pathology, number of cores, and left versus right breast were not associated with migration status (P> 0.10). Global fatty breast density (P= 0.025) and biopsy in the inner region of breast (P = 0.031) were associated with marker migration. Superior biopsy approach (P= 0.025), locally heterogeneous breast density, and t-shaped biopsy markers (P= 0.035) were significant for no marker migration.ConclusionsMultiple factors were found to influence marker migration. An overall migration rate of 13% supports endeavors of research groups actively developing new biopsy marker designs for improved resistance to migration.Key Points• Breast biopsy marker migration is documented in 13% of 268 procedures.• Marker migration is affected by physical, biological, and pathological factors.• Breast density, marker shape, needle approach etc. affect migration.• Study demonstrates marker migration prevalence; marker design improvements are needed.