Intestinal retentive devices have applications ranging from sustained oral drug delivery systems to indwelling ingestible medical devices. Current strategies to retain devices in the small intestine primarily focus on chemical anchoring using mucoadhesives or mechanical coupling using expandable devices or structures that pierce the intestinal epithelium. Here, the feasibility of intestinal retention using devices containing villi‐inspired structures that mechanically interlock with natural villi of the small intestine is evaluated. First the viability of mechanical interlocking as an intestinal retention strategy is estimated by estimating the resistance to peristaltic shear between simulated natural villi and devices with various micropost geometries and parameters. Simulations are validated in vitro by fabricating micropost array patches via multistep replica molding and performing lap‐shear tests to evaluate the interlocking performance of the fabricated microposts with artificial villi. Finally, the optimal material and design parameters of the patches that can successfully achieve retention in vivo are predicted. This study represents a proof‐of‐concept for the viability of micropost‐villi mechanical interlocking strategy to develop nonpenetrative multifunctional intestinal retentive devices for the future.
Melasma is a common chronic relapsing pigmentary disorder primarily affecting women. It is highly prevalent in the Indian skin type with a large psychological impact. Treatment is challenging with no cure available yet. Even so, treatment modalities are many and varied-each promising more than the last. We analyzed the understanding of photoprotection, topical and oral treatments, and procedures such as microneedling, laser resurfacing, and peelings that serve as the primary methods for controlling and preventing this illness. While there are a few well established treatments such as hydroquinone and triple combination creams, side effects impede their long-term use. Safer alternatives have now come up which can be used for extended durations such as kojic acid, rucinol, and cysteamine cream. Lasers and light therapies have slowly become an essential component of melasma management. In this manuscript, we attempt to provide a critical and concise review of the current updates in melasma therapy.
Estimates of vessel leakiness are valuable in assessing the effect of anti-angiogenic drugs on vascular permeability. Here we present image processing methods to quantify vessel permeability to albumin in whole mount or thick section specimens.Mice with endometrial implants in the peritoneal wall [1,2] were euthanized 7 days postimplantation and injected I.V. with FITC-conjugated albumin. Nine of the mice had been treated with an angiogenesis inhibitor and eight mice were untreated controls. Vessels were imaged using confocal microscopy (Figs. 1, 2).To identify albumin filled vessels serial sections were globally thresholded to distinguish background from albumin. Pixels were categorized as belonging to vessel contents if they were within an apparent vessel with a minimum width of 5-8 microns in any direction, independent of length and vessel morphology.To determine the permeability coefficient for vessels, 12 test line segments were applied passing through the vessel center in different orientations (Fig 1). An exponential decay curve fit was performed on a histogram of intensity vs. distance (Fig 3) along each test segment. The exponential decay curve is in the form of e (-x/τ) , where x is the distance from the vessel boundary to the free albumin, and τ is the lifetime decay, referred to in this study as the permeability coefficient. Larger coefficients correspond to greater amounts of free albumin present outside the vessel wall, indicating higher vessel permeability. The highest and lowest permeability coefficients were excluded for each image section analyzed. The permeability coefficients of the treated and untreated groups were then averaged.For comparison, 3-D connectivity algorithm was used to distinguish between intravascular and leaked albumin pixels. Pixels above threshold that were connected to a minimum number of voxels (corresponding to a minimum width of 5-8 microns in any direction) of above-threshold pixels in x, y, and z were considered to represent vessel contents (VC). All other pixels above threshold were counted as free albumin (FA). The mean ratio of free albumin to vessel contents pixels (FA/VC) was calculated.
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