Stochastic to Deterministic: A straightforward approach to create serially perfusable multiscale capillary beds.

Generation of in vitro tissue models with serially perfused hierarchical vasculature would allow greater control of fluid perfusion throughout the network and enable direct mechanistic investigation of vasculogenesis, angiogenesis, and vascular remodeling. In this work, we have developed a method to produce a closed, serially perfused, multiscale vessel network embedded within an acellular hydrogel. We confirmed that the acellular and cellular gel-gel interface was functionally annealed without preventing or biasing cell migration and endothelial self-assembly. Multiscale connectivity of the vessel network was validated via high-resolution microscopy techniques to confirm anastomosis between self-assembled and patterned vessels. Lastly, using fluorescently labeled microspheres, the multiscale network was serially perfused to confirm patency and barrier function. Directional flow from inlet to outlet man-dated flow through the capillary bed. This method for producing closed, multiscale vascular networks was developed with the intention of straightforward fabrication and engineering techniques so as to be a low barrier to entry for researchers who wish to investigate mechanistic questions in vascular biology. This ease of use offers a facile extension of these methods for incorporation into organoid culture, organ-on-a-chip (OOC) models, and bioprinted tissues.

pH-responsive delivery of anti-metastatic niclosamide using mussel inspired polydopamine nanoparticles.

Niclosamide (Nic), an FDA approved antihelminthic drug, is being repurposed as a potent anti-cancer and anti-inflammatory agent. Niclosamide exhibits anti-cancer activity in multiple cancer types, including breast, colon, and prostate cancers. Niclosamide, a BCS II drug, is practically insoluble in water and sparingly soluble in organic solvents (ethanol, dimethyl sulfoxide), leading to limited therapeutic applications, and necessitates the need for a drug carrier. Herein, we report the preparation of polydopamine nanoparticles loaded with niclosamide (Nic-PDA NPs). The designed formulation had a very high loading efficiency (~30%) and entrapment efficiency close to 90%. The average hydrodynamic diameter of Nic-PDA NPs was 146.3 nm, with a narrow size distribution (PDI = 0.039). The formulation exhibited a pH-dependent drug release profile, with ~35% drug released at pH 7.4 after 120 h, compared to > 50% at pH 5.5 in simulated physiological conditions. The NPs exhibited time-dependent cellular uptake and were primarily localized in the cytoplasm. The formulation exhibited comparable cytotoxicity in MDA-MB-231 cells (IC50 = 2.73 µM, 36 h), and inhibited the migration of cancer cells significantly compared to the free drug and unloaded PDA NPs. Furthermore, the unloaded NPs exhibited excellent in vivo compatibility. The study establishes a rigorously optimized protocol for the synthesis of Nic loaded PDA NPs. The biocompatibility, anti-migratory efficacy, and the in vivo non-toxic nature of PDA has been well demonstrated.

Comprehensive Evaluation of Degradable and Cost-Effective Plasmonic Nanoshells for Localized Photothermolysis of Cancer Cells.

Integrating the concept of biodegradation and light-triggered localized therapy in a functional nanoformulation is the current approach in onco-nanomedicine. Morphology control with an enhanced photothermal response, minimal toxicity, and X-ray attenuation of polymer-based nanoparticles is a critical concern for image-guided photothermal therapy. Herein, we describe the simple design of cost-effective and degradable polycaprolactone-based plasmonic nanoshells for the integrated photothermolysis as well as localized imaging of cancer cells. The gold-deposited polycaprolactone-based plasmonic nanoshells (AuPCL NS) are synthesized in a scalable and facile way under ambient conditions. The synthesized nanoshells are monodisperse, fairly stable, and highly inert even at five times (250 µg/mL) the therapeutic concentration in a week-long test. AuPCL NS are capable of delivering standalone photothermal therapy for the complete ablation of cancer cells without using any anticancerous drugs and causing toxicity. It delivers the same therapeutic efficacy to different cancer cell lines, irrespective of their chemorefractory status and also works as a potential computed tomography contrast agent for the integrated imaging-directed photothermal cancer therapy. High biocompatibility, degradability, and promising photothermal efficacy of AuPCL NS are attractive aspects of this report that could open new horizons of localized plasmonic photothermal therapy for healthcare applications.

Pharmaceutical feasibility and flow characteristics of polymeric non-spherical particles.

Last decade has seen emergence of particle shape as a critical design parameter to overcome several long standing problems associated with particulate drug delivery- non-specific drug effects, RES uptake, poor bioavailability, achieving controlled release profiles, predictable degradation profiles, longer circulation time and zero order release kinetics to name a few. Non-spherical particles have been synthesized by techniques ranging from classical solvent evaporation to specialized techniques like film stretching and PRINT®. Non-spherical particles tend to show a difference in macrophage uptake, adhesion to target cells and distribution in vivo. This review also discusses these effects and its implications. Lastly, the impact of particle aspect ratio and other shape-governed parameters on flow properties, dispersion viscosities and other pharmaceutically relevant aspects have been briefly explained. Although there are no thumb rules yet, modern and classical literature on behavior of non-spherical particles has been reviewed and the observations have been trend-lined.