Bentonite- and Palygorskite-Based Gels for Topical Drug Delivery Applications

Bentonite or palygorskite-based hydrogels have recently been suggested as a strategy to increase bioavailability and control the retention and release of therapeutic candidates. In this work, clay-based hydrogels loaded with diclofenac acid nanocrystals have been successfully designed and developed. The aim was to improve diclofenac solubility, its dissolution rate and to enhance its local bioavailability after topical application. For this purpose, diclofenac acid nanocrystals were prepared by wet media milling technology and then loaded into inorganic hydrogels based on bentonite and/or palygorskite. Diclofenac acid nanocrystals were characterized by morphology, size, and zeta potential. Moreover, rheological behavior, morphology, solid state, release studies, and in vitro skin penetration/permeation of diclofenac acid nanocrystals-loaded hydrogels were performed. The hydrogels were characterized by a crystalline structure, and demonstrated that the inclusion of diclofenac in clay-based hydrogels resulted in an increased thermal stability. The presence of both palygorskite and bentonite reduced nanocrystal mobility, and consequently its release and penetration into the skin. On the other hand, bentonite- or palygorskite-based hydrogels revealed great potential as an alternative strategy to enhance topical bioavailability of DCF nanocrystals, enhancing their penetration to the deeper skin layers

Nanocrystals as an effective strategy to improve Pomalidomide bioavailability in rodent

Pomalidomide (POM) is an FDA-approved immunomodulatory imide drug (IMiDs) an it is effectively used in the treatment of multiple myeloma. IMiDs are analogs of the drug thalidomide and they have been repurposed for the treatment of several diseases such as psoriatic arthritis and Kaposi Sarcoma. In recent years, IMiDs have been also evaluated as a new treatment for neurological disorders with an inflammatory and neuroinflammatory component. POM draws particular interest for its potent anti-TNF-α activity at significantly lower concentrations than the parent compound thalidomide. However, POM's low water solubility underpins its low gastrointestinal permeability resulting in irregular and poor absorption. The purpose of this work was to prepare a POM nanocrystal-based formulation that could efficiently improve POM's plasma and brain concentration after intraperitoneal injection. POM nanocrystals prepared as a nanosuspension by the media milling method showed a mean diameter of 219 nm and a polydispersity index of 0.21. POM's nanocrystal solubility value (22.97 µg/mL) in phosphate buffer was about 1.58 folds higher than the POM raw powder. Finally, in vivo studies conducted in adult Male Sprague-Dawley rats indicated that POM nanocrystal ensured higher and longer-lasting drug levels in plasma and brain when compared with POM coarse suspension

Morphological and Postural changes in the foot during pregnancy and puerperium : a longitudinal study

The aim of this study is to observe the morphological and postural changes to the foot that take place during pregnancy and the puerperium. Method: In this descriptive, observational, longitudinal study, we analysed 23 pregnant women, with particular attention to morphological and postural aspects of the foot, at three time points during and after pregnancy: in weeks 9-13 of gestation, weeks 32-35 of gestation and weeks 4-6 after delivery. The parameters considered were changes in foot length, the Foot Posture Index (FPI) and the Hernández Corvo Index, which were analysed using a pedigraph and taking into account the Body Mass Index (BMI). The same procedure was conducted in each review. Results: The statistical analyses obtained for each foot did not differ significantly between the three measurement times. A pronator-type footprint was most frequently observed during the third trimester of pregnancy; it was predominantly neutral during the postpartum period. Statistically significant differences between the measurement times were obtained in the right foot for cavus vs. neutral foot type (between the first and third trimesters and also between the first trimester and the puerperium) (in both cases, p < 0.0001). Conclusions: Foot length increases in the third trimester and returns to normal in the puerperium. According to FPI findings, the third trimester of pregnancy is characterised by pronation, while the posture returns to neutrality during the postpartum period. During pregnancy, the plantar arch flattens, and this persists during the puerperium. The incidence of cavus foot increases significantly in the third trimester and in the puerperium

Measuring adherence to inhaled control medication in patients with asthma: Comparison among an asthma app, patient self‐report and physician assessment

Background Previous studies have demonstrated the feasibility of using an asthma app to support medication management and adherence but failed to compare with other measures currently used in clinical practice. However, in a clinical setting, any additional adherence measurement must be evaluated in the context of both the patient and physician perspectives so that it can also help improve the process of shared decision making. Thus, we aimed to compare different measures of adherence to asthma control inhalers in clinical practice, namely through an app, patient self-report and physician assessment. Methods This study is a secondary analysis of three prospective multicentre observational studies with patients (≥13 years old) with persistent asthma recruited from 61 primary and secondary care centres in Portugal. Patients were invited to use the InspirerMundi app and register their inhaled medication. Adherence was measured by the app as the number of doses taken divided by the number of doses scheduled each day and two time points were considered for analysis: 1-week and 1-month. At baseline, patients and physicians independently assessed adherence to asthma control inhalers during the previous week using a Visual Analogue Scale (VAS 0–100). Results A total of 193 patients (72% female; median [P25–P75] age 28 [19–41] years old) were included in the analysis. Adherence measured by the app was lower (1 week: 31 [0–71]%; 1 month: 18 [0–48]%) than patient self-report (80 [60–95]) and physician assessment (82 [51–94]) (p 0.05). There was a moderate correlation between patient self-report and physician assessment (ρ = 0.596, p < 0.001). Conclusions Adherence measured by the app was lower than that reported by the patient or the physician. This was expected as objective measurements are commonly lower than subjective evaluations, which tend to overestimate adherence. Nevertheless, the low adherence measured by the app may also be influenced by the use of the app itself and this needs to be considered in future studies.info:eu-repo/semantics/publishedVersio

Formulation and characterization studies of trimethyl chitosan / sodium alginate nanoparticles for targeted drug delivery

The objective of this study was to develop positively charged nanoparticles based on trimethyl chitosan and sodium alginate, as drug delivery systems able to interact with the sialic residues of the mucous membranes. Nanoparticles were prepared with the ionotropic gelation method, using sodium tripolyphosphate as cross-linking agent. Ten different nanoparticle formulations were developed by varying the concentration of one component, while keeping constant the two others, or by varying the ratio between the three components. The aim of this formulation study was to determine the effect of both polymers and cross-linker concentration and their ratios on nanoparticle dimensional parameters, such as mean size and size distribution, and surface charge. Overall results of the formulations study indicated that samples prepared with 2 mg/mL trimethyl chitosan concentration and different sodium alginate concentrations, namely 1 or 2 mg/mL, showed the best dimensional features, while the optimum concentration of cross-linking agent was 1 mg/mL. Moreover, nanoparticle showed a positive charge surface, useful to interact with mucosal membranes