Solid Composite Material for Delivering Viable Cells into Skin Tissues via Detachable Dissolvable Microneedles

Abstract

Delivering cells to desired locations in the body is needed for disease treatments, tissue repairs, and various scientific investigations such as animal models for drug development. Here, we report the solid composite material that when embedded with viable cells, can temporarily keep cells alive. Using the material, we also show the fabrication of detachable dissolvable microneedles (DMNs) that can instantly deliver viable cells into skin tissue. B16-F10-murine-melanoma (B16-F10) and human-embryonickidney-293T (HEK293T) cells embedded in the solid matrix of the hyaluronic/polyvinylpyrolidone/maltose (HA/PVP/maltose) mixture show 50.6 ± 12.0 and 71.0 ± 5.96% survivals, respectively, when kept at 4 °C for 24 h. Detachable DMNs made of the HA/PVP/maltose mixture and loaded with B16-F10-cells were constructed, and the obtained DMN patches could detach the cell-loaded needles into the skin within 1 min of patch application. In vivo intradermal tumorgrafting mice with the DMNs containing 800 cells of B16-F10 developed tumors 10 times bigger in volume than tumors induced by hypodermic needle injection of suspension containing 100,000 cells. We anticipate this work to be a starting point for viable cell encapsulation in the solid matrix and viable cell delivery via DMNs.

Application of microneedle patches for drug delivery; doorstep to novel therapies

“…The solid backbone of separable MNs is made of non-degradable materials while arrowhead tips are fabricated using degradable scaffolds. 51 Pukfukdee et al 62 designed a separable hyaluronic acid-polyvinylpyrrolidone-maltose as a solid matrix for cell delivery into the cutaneous tissue. In this regard, they encapsulated murine melanoma cells (B16-F10) and found the successful delivery of melanoma cells by cell-loaded needles into the hypodermic region.…”

Delivery and diffusion of retinal in dermis and epidermis through the combination of prodrug nanoparticles and detachable dissolvable microneedles

“…Hyaluronic acid (HA, injection grade, Shandong Focuschem Biotech Co., Ltd., Shandong Sheng, China) was mixed with each of the following materials: polyvinyl pyrrolidone (PVP K30, average Mw 40,000, Sigma-Aldrich, Germany), polyvinyl alcohol (PVA, average Mw 146,000-186,000, Sigma-Aldrich), carboxymethyl cellulose (CMC, Dow Chemical Thailand Ltd, Bangkok, Thailand), sericin (Seritech Co., Ltd, Bangkok, Thailand) and maltose (Sigma-Aldrich), at two ratios. Solution of selected materials was prepared in water and the obtained solution was used to prepare microneedle arrays via the molding method as previously described [31,35]. The total of 11 formulations of needle matrix material were experimented and they include (expressed here as weight percentages) 100% HA, 50% PVP + 50% HA, 25% PVP + 75% HA, 50% maltose + 50% HA, 25% maltose + 75% HA, 50% PVA + 50% HA, 25% PVA + 75% HA, 50% CMC + 50% HA, 25% CMC + 75% HA, 50% sericin + 50% HA and 25% sericin + 75% HA.…”

Microneedle arrays integrated with living organisms for smart biomedical applications

“…For example, Wanichwecharungruang et al . utilized dissolving MNAs made of hyaluronate (HA)/polyvinyl pyrrolidone (PVP)/maltose to deliver cancer cells into mice models for tumor grafting ( Figure 6 A ) 88 . After drying at 4 °C, the MNAs could maintain the viability of the encapsulated B16-F10-murine-melanoma at about 38.8% for 7 days.…”

“…Cell transplantation using these B16-F10-cell-loaded MNAs displayed higher tumorigenesis efficiency and larger tumor formation using less cells compared to the hypodermic needle injection. Reproduced with permissions from American Chemical Society 2020 88 . B (i) MSCs were delivered into localized skin by a core-shell MNA for would healing.…”