The present study investigated the transdermal delivery of donepezil hydrochloride across dermatomed porcine ear skin using passive and physical enhancement techniques. In vitro permeation studies were performed on Franz diffusion cells. Microneedles were fabricated in the lab using a polymeric blend of polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP). The fabricated microneedles were characterized using SEM. Effect of PVA-PVP microneedles and ablative laser (P.L.E.A.S.E) alone, and in combination with anodal iontophoresis on the delivery of donepezil hydrochloride was investigated. Scanning electron microscopy, histology, methylene blue staining, and confocal laser microscopy were used to characterize the microchannels created in the skin. Permeation of donepezil after passive delivery was found to be 26.87 ± 3.97 µg/sq.cm. Microneedles, laser, and iontophoresis significantly increased the permeation to 282.23 ± 8.28 µg/sq.cm, 1562 ± 231.8 µg/sq.cm and 623.4 ± 21.3 µg/sq.cm. Also, a significantly higher permeation was achieved with microneedles and laser in combination with iontophoresis (1000 ± 160.9 µg/sq.cm and 1700.4 ± 189.43 µg/sq.cm respectively). A sharp increase in flux was observed with a combination of skin microporation and iontophoresis, however, the same was not observed for iontophoretic delivery alone. Thus, flux can be successfully tailored with a combination of skin microporation and iontophoresis to suit patient needs.Developability assessment of therapeutic mAb candidates before entering CMC development mitigates the risk of later failure because of manufacturing and stability issues. For mAbs derived from library based screenings, such evaluation starts with the first panning and ends with the selection of a lead candidate. This candidate should show, amongst others, high affine target binding and beneficial conformational as well as chemical stability. In addition, colloidal stability, reflected by the self-interaction propensity, should be superior in order to reduce aggregate formation and unacceptably high viscosity at elevated protein concentrations. Here, we present a study demonstrating the application of self-interaction bio-layer interferometry (SI-BLI) in a developability assessment, including the evaluation of preformulations. We reveal that the formulation rankings based on SI-BLI, DLS and viscosity measurements correlate. SI-BLI provides a deeper understanding of influencing factors on mAb self-interaction such as ionic strength or cation species. The attractive mAb self-interaction propensity was significantly more suppressed by Mg2+ compared to Na+. SI-BLI can be performed in high throughput with minimal material and sample preparation needs. Therefore, it can be applied in early stages of developability assessment going beyond the use of a platform formulation and a small number of analysis, to screen more parameters before proceeding with candidate selection and further extensive development.Application of amino acids-immobilized porous materials for drug delivery studies has been attracted a lot of attention in the recent years. In this study, amino acids-grafted graphene foams were prepared by anchoring of Alanine (Ala), Cysteine (Cys) and Glycine (Gly) amino acids on the surface of graphene oxide (GO) nanostructures and used as the novel biocompatible carriers to control releasing of the cisplatin as the cytotoxic anticancer drug. The characterization of prepared compounds was done by the FT-IR, Raman, TGA, N2 adsorption-desorption isotherms, SEM, and TEM techniques. Adsorption and in vitro release behavior of amino acids-functionalized foams were studied using ICP standard method. The results show that the drug loading amount and the drug releasing rate are significantly enhanced upon functionalization process. The Ala-Foam sample with the larger surface area and pore volume showed a higher loading content (4.53%) than other samples. In addition, the MTT test on the two MCF-7 and HepG2 human cancer cell lines exhibited an acceptable biocompatibility and sustainable drug releasing from the carriers up to 48 h, leading to the dosage frequency decrease and the patient compliance improvement.The use of nanomedicines to induce immunogenic cell death is a new strategy that aims to increase tumor immunogenicity and thereby prime tumors for further immunotherapies. In this study, we developed a nanoparticle formulation for combinatory chemotherapy and photothermal therapy based only on materials previously used in FDA-approved products and investigated the effect of the combinatory therapy on the growth inhibition and induction of immunogenic cell death in human MDA-MB-231 breast cancer cells. The formulation consists of ~108-nm nanoparticles made of poly(lactic acid)-b-methoxy poly(ethylene glycol) which carry doxorubicin for chemotherapy and indocyanine green for photothermal therapy. A 0.3 mg/mL suspension of NPs increased the medium temperature up to 10 °C upon irradiation with an 808-nm diode laser. In vitro studies showed that combination of laser assisted indocyanine green-mediated photothermal therapy and doxorubicin-mediated chemotherapy effectively eradicated cancer cells and resulted in the highest level of damage-associated molecular pattern presentation (calreticulin, high mobility group box 1, and adenosine triphosphate) compared to the individual treatments alone. These results demonstrate that our nanoparticle-mediated combinatory approach led to the most intense immunogenic cell death when compared to individual chemotherapy or photothermal therapy, making it a potent option for future in vivo studies in combination with cancer immunotherapies.Phototherapy exerts its anticancer effects by converting laser radiation energy into hyperthermia or reactive singlet oxygen (1O2). In this study, we developed chitosan nanoparticles (CS NPs) encapsulating both photothermal (IR780) and photodynamic (5-Aminolevulinic acid (5-ALA)) reagents for photothermally enhanced photodynamic therapy by noninvasive oral administration. https://www.selleckchem.com/products/hro761.html The 5-ALA&IR780@CS NPs were stable in acidic conditions similar to the gastric environment, which greatly improved drug oral absorption and local accumulation in subcutaneous mouse colon tumors (CT-26 cells) following oral gavage. Mechanistic studies revealed that the co-delivery system can lead to photothermally enhanced photodynamic effects against cancer cells by increasing oxidative stress, including the elevation of ROS, superoxide and 1O2 production. Additionally, significant therapeutic efficacy for cancer treatment were observed in vivo after oral administration of 5-ALA&IR780@CS NPs, without causing any overt adverse effects. Our work highlights the great potential of photothermally enhanced photodynamic therapy by CS NPs for colon cancer management via oral route.