Markerlund8047

In particular, the mechanistic salt model can be used to aid in screening and salt form selection where the aim is to mitigate effects of ARAs.The synergy between directed chemotherapy and thermal therapy (both magnetic hyperthermia and photothermia) mediated by a nanoassembly composed of functionalized biomimetic magnetic nanoparticles (BMNPs) with the chemotherapeutic drug doxorubicin (DOXO) covered by the polymer poly(lactic-co-glycolic acid) (PLGA), decorated with TAT peptide (here referred to as TAT-PLGA(DOXO-BMNPs)) is explored in the present study. The rationale behind this nanoassembly lies in an optimization of the nanoformulation DOXO-BMNPs, already demonstrated to be more efficient against tumor cells, both in vitro and in vivo, than systemic traditional therapies. By embedding DOXO-BMNPs into PLGA, which is further functionalized with the cell-penetrating TAT peptide, the resulting nanoassembly is able to mediate drug transport (using DOXO as a drug model) and behaves as a hyperthermic agent (induced by an alternating magnetic field (AMF) or by laser irradiation with a laser power density of 2 W/cm2). Our results obtained using the HepG2 cell line show that there is a synergy between chemotherapy and thermal therapy that results in a stronger cytotoxic effect when compared to that caused by the soluble DOXO. This is probably due to the enhanced DOXO release occurring upon the application of the thermal therapy, as well as the induced local temperature rise mediated by BMNPs in the nanoassembly following exposition to AMF or to near-infrared (NIR) laser irradiation. These results represent a proof of concept demonstrating that TAT-PLGA(DOXO-BMNPs) can be used to efficiently combine therapies against tumor cells, which is a step forward in the transition from systemic to local treatments.Cancer, a group of diseases responsible for the second largest cause of global death, is considered one of the main public health problems today. Despite the advances, there are still difficulties in the development of more efficient cancer therapies and fewer adverse effects for the patients. In this context, nanobiotechnology, a materials science on a nanometric scale specified for biology, has been developing and acquiring prominence for the synthesis of nanocarriers that provide a wide surface area in relation to volume, better drug delivery, and a maximization of therapeutic efficiency. Among these carriers, the ones that stand out are those focused on the activation of the immune system. The literature demonstrates the importance of this system for anticancer therapy, given that the best treatment for this disease also activates the immune system to recognize, track, and destroy all remaining tumor cells.The lyoprotective effects of mannitol and lactose have been evaluated in the production of sildenafil citrate liposomes. Liposomes were prepared by mixing the components under ultrasonic agitation, followed by a transmembrane pH gradient for remote drug loading. Mannitol and lactose, as compared to sucrose and trehalose, were used as the stabilizing agents, and different freeze-drying cycles were assayed. The remaining moisture and the thermal characteristics of the lyophilized samples were analyzed. Size, entrapment efficiency, biocompatibility, and cell internalization of original and rehydrated liposomes were compared. The type of additive did not affect the biocompatibility or cell internalization, but did influence other liposome attributes, including the thermal characteristics and the remaining moisture of the lyophilized samples. A cut-off of 5% (w/w) remaining moisture was an indicator of primary drying completion-information useful for scaling up and transfer from laboratory to large-scale production. Lactose increased the glass transition temperature to over 70 °C, producing lyoprotective effects similar to those obtained with sucrose. MLN7243 Based on these results, formulations containing liposomes lyophilized with lactose meet the FDA's requirements and can be used as a biocompatible and biodegradable vehicle for the pulmonary delivery of therapeutic doses of sildenafil citrate.Complementary and alternative medicines represent an interesting field of research on which worldwide academics are focusing many efforts. In particular, the possibility to exploit pharmaceutical technology strategies, such as the nanoencapsulation, for the delivery of essential oils is emerging as a promising strategy not only in Italy but also all over the world. The aim of this work was the development of nanostructured lipid carriers (NLC) for the delivery of essential oils (Lavandula, Mentha, and Rosmarinus) by intranasal administration, an interesting topic in which Italian contributions have recently increased. Essential oil-loaded NLC, projected as a possible add-on strategy in the treatment of neurodegenerative diseases, were characterized in comparison to control formulations prepared with Tegosoft CT and Neem oil. Homogeneous (polydispersity index, PDI less then 0.2) nanoparticles with a small size ( less then 200 nm) and good stability were obtained. Morphological and physical-chemical studies showed the formation of different structures depending on the nature of the liquid oil component. In particular, NLC prepared with Lavandula or Rosmarinus showed the formation of a more ordered structure with higher cytocompatibility on two cell lines, murine and human fibroblasts. Taken together, our preliminary results show that optimized positively charged NLC containing Lavandula or Rosmarinus can be proposed as a potential add-on strategy in the treatment of neurodegenerative diseases through intranasal administration, due to the well-known beneficial effects of essential oils and the mucoadhesive properties of NLC.High medication costs are one of the major barriers to patient adherence. Medication affordability might be improved by generic substitution. The aim of this study was to assess the effectiveness of the implementation of generic substitution mechanisms in Poland. This was a retrospective analysis of nationwide real-world big data corresponding to dispensation of metformin preparations in 2019 in Poland. Relevant prescription and dispensation data were compared to assess the prevalence of generic substitution and its economic consequences. Among the 1,135,863 e-prescriptions analysed, a generic substitution was found in only 4.81% of the packs dispensed, based on e-prescriptions issued for metformin under its originator version and 2.73% under generic drugs. It is estimated that if these values were applied to the total Polish drug market, patients could lose the opportunity to lower their co-payment by 15.91% and the national payer to reduce its reimbursement expenditures by 8.31%. Our results point at the suboptimal implementation of generic substitution in Poland. Therefore, relevant actions need to be taken in order to maximise the benefits provided by this mechanism. It could not only lead to the win-win scenario in which both patients and the national payer are secured substantial savings, but it could also have a positive impact on patient adherence.Lipidic implants are valuable controlled delivery systems that present good biocompatibility and are useful for long-lasting therapies. However, these promising systems can present inflexible drug release profiles that limit their performance. Thus, finding new materials to overcome this drawback is crucial. Herein, lipidic implants containing caffeine and poorly soluble salicylic acid and rutin were developed. The inclusion of Gelucire® 50/02, sucrose, and two biobased ionic liquids, [Cho][Phe] and [Cho][Glu], were evaluated as a mean to improve the performance of the systems. The formulation procedure, dye content distribution, drug content, drug release, water content, and lipidic erosion of the developed systems were assessed. AFM analysis of the implants containing ILs was also performed. The results demonstrated that neither Gelucire® 50/02 nor sucrose were suitable tools to improve the drug release profile. In contrast, the ILs proved to be promising materials for multiple reasons; not only did they facilitate the formulation and incorporation of the studied drugs into the implants, but they also allowed a more suitable release profile, with [Cho][Glu] allowing a higher drug release due to its ability to increase surface wrinkling. Hence, this study showcases ILs as multitalented materials in lipid-based drug implants.The feasibility of using respirable bacteriophage (phage) powder to treat lung infections has been demonstrated in animal models and clinical studies. This work investigated the influence of formulation compositions and excipient concentrations on the aerosol performance and storage stability of phage powder. An anti-Acinetobacter baumannii phage vB_AbaM-IME-AB406 was incorporated into dry powders consisting of trehalose, mannitol and L-leucine for the first time. The phage stability upon the spray-drying process, room temperature storage and powder dispersion under different humidity conditions were assessed. In general, powders prepared with higher mannitol content (40% of the total solids) showed a lower degree of particle merging and no sense of stickiness during sample handling. These formulations also provided better storage stability of phage with no further titer loss after 1 month and less then 1 log titer loss in 6 months at high excipient concentration. Mannitol improved the dispersibility of phage powders, but the in vitro lung dose dropped sharply after exposure to high-humidity condition (65% RH) for formulations with 20% mannitol. While previously collected knowledge on phage powder preparation could be largely extended to formulate A. baumannii phage into inhalable dry powders, the environmental humidity may have great impacts on the stability and dispersion of phage; therefore, specific attention is required when optimizing phage powder formulations for global distribution.Dermatophytosis is a fungal infection of skin, nails and hair. Treatments can be long and infections are often recurrent, and novel treatments are desirable. Here we tested the use of polymeric films that can be sprayed on the skin for the prevention and treatment of dermatophytosis. The two polymers selected were ABIL T Quat 60 and Eudragit E100, which were tested ex vivo using a porcine skin model, and in vitro using microbiological and microscopy techniques. Acceptability of the polymeric films was tested on the skin of healthy volunteers. The results showed that ABIL and Eudragit films prevented and treated fungal skin infections. Whilst polymer films may provide a physical barrier that prevents fungal colonization, it was shown that both polymers are active antifungals ex vivo and in vitro and have intrinsic antifungal activity. For ABIL, we also established that this polymer binds essential nutrients such as metal ions and sugars, thereby restricting the growth of fungi. When applied to healthy subjects' skin, the polymeric films neither modified the skin color nor increased trans-epidermal water loss, suggesting a low potential for skin irritation, and the approach was generally found to be acceptable for use by the volunteers. In conclusion, we developed a novel strategy for the potential prevention and treatment of dermatophytosis.