Formulation and in Vitro Characterisation of Fungal Chitosan Nanoparticles Coated With Zein for Improved Oral Delivery of Selenoamino Acids

Selenium (Se) is an essential micronutrient in both human and animal nutrition that exists in a wide array of different forms, both organic and inorganic. Selenoamino acids (SeAAs), such as selenocystine (SeCys2), selenomethionine (SeMet), and methylselenocysteine (MSC) are organic species with reported health benefits of cancer prevention, increased fertility and improved immunological status. However, supplementation of SeAAs can be challenging, due to their reported narrow therapeutic range of indices, low bioavailability and increased susceptibility to oxidation. To address this, SeAAs were encapsulated into nanoparticles (NPs) to lower their toxicity profiles in comparison to their native form, in addition to offering them protection from the harsh conditions present in the gastrointestinal tract. The ionotropic gelation method was employed to produce NPs, using the cationic polyelectrolyte chitosan (Cs) crosslinked with the polyanion tripolyphosphate (TPP). The NP physicochemical properties were optimised using a Design of Experiments (DoE) and mathematical modelling approach. First, a central composite design (CCD) was used to identify a feasible region in which unloaded NPs with target properties for oral delivery (size~300 nm, PDI \u3c 0.5 and ZP \u3e 30 mV) could be achieved, indicating that optimum conditions to be 6:1 mass ratios of Cs:TPP. Following that, SeMet was used as a prototype encapsulant and a second DoE approach was employed, namely a Box Behnken design (BBD). In that study, Cs:TPP ratio, Cs solvent pH, and drug load concentration were independently varied and the dependent variables assessed were encapsulation efficiency (EE%), particle size, PDI and ZP. The BBD highlighted the optimum conditions for NP production, although EE% remained relatively low (≈40 %). By varying the pH of the ionotropic solution components and coating the NPs with zein (a prolamine rich protein), EE% was doubled (≈80 %), diameters increased from 187±58nm to 377±47nm and PDI and ZP values were maintained. The formulation performed well indicating good suitability for oral delivery, in terms of stability, cytotoxicity (intestinal and liver cell lines) and release profiles, as determined by in vitro techniques. The models generated from the BBD were then applied to the SeAAs, SeCys2 and MSC and further refinement of the zein coating was investigated. NPs with similar physicochemical properties to those of SeMet loaded Cs were produced, indicating the strength of the DoE models and their usefulness in formulation design. These NPs also performed well in in vitro assessments for stability and release profiles. However, SeCys2 showed cytotoxicity to liver cell lines which was reduced after encapsulation within the NP matrix, inferring its protective effects and thus use as a delivery system. Chitin was extracted from the cultivated mushroom Agaricus bisporus in order to derive fungal Cs (fCs) with equivalent physicochemical properties to the commercial Cs (CL113) that had been employed for NP production. fCs with comparable properties to CL113 were produced, although fCs possessed a higher molecular weight (MW) (180±19 vs 110±4 kDa). Trimethyl chitosan was then synthesised from the fCs and assessed for permeation enhancing capabilities on intestinal cell monolayer models, which implicated its potential application as a permeation enhancer. fCs was used for the production of synthetic SeCys2 loaded NPs using the knowledge gained from the previously developed DoE models and in vitro methodologies. Lastly, a preliminary study to assess the feasibility of Irish mushrooms providing Se species for supplementation purposes was conducted, implicating them as a viable source for SeCys2

Oral Prevention and Management of Oral Healthcare

Oral health is an important factor in the maintenance of general health, wellbeing, and overall quality of life. Envisioning a transformational change in the management of oral healthcare, this Special Issue is focused on oral health and prevention and their impact on clinical practice current oral health literacy and policies. Preventive strategies should be implemented to reduce oral problems, due to the negative consequences on individuals and communities in terms of pain and suffering, functional impairments, and reduced quality of life

Minimally invasive orthodontics: elastodontic therapy in a growing patient affected by Dentinogenesis Imperfecta

AIM: The aim of the study was to report the use of an elastodontic therapy in a growing patient affected by Dentinogenesis Imperfecta, second class malocclusion, deep bite and lower arch crowding from the deciduous dentition to permanent one. CASE REPORT: At first, the 5-year-old patient was treated with an elastodontic device known as "Nite-Guide". When the patient was 7 years old, during her first permanent molars and incisors eruption and after optimal house-practices, an Occlus-o-Guide Series G was placed at night and on daylight (two hours a day) performing exercises aimed to activate facial muscles and facilitate the deep bite reopening. At 9 years of age, with totally deep bite resolution, she used the Occluso-Guide only at night to hold down previous results and follow patient's dental growth. At 11 years of age, after successful teeth switching, we prescribed an Occlus-o-Guide Series N, which is functional for permanent dentition and guaranteed an eruptive guide for last dental elements. CONCLUSIONS: This clinic case could be considered an example of approach for all those patients with systemic and/or dental diseases that do not allow adequate dental retention, which is necessary for most orthodontic appliances; elastodontic devices do not require adequate dental retention and define a minimum intervention on the surfaces of the teeth

The Ethics of Deferred Prosecution Agreements for MNEs Culpable of Foreign Corruption: Relativistic Pragmatism or Devil’s Pact?

Deferred prosecution agreements (DPAs) are legal means, alternative to trial, for the resolution of criminal business cases. Although DPAs are increasingly used in the US and are spreading to other jurisdictions, the ethics of DPAs has hardly been subjected to critical scrutiny. We use a multidisciplinary approach straddling the line between philosophy and law to examine the ethics of DPAs used to resolve cases of multinational enterprises’ (MNEs) foreign corruption. Deontologically, we argue that the normativity of DPAs raises critical concerns related to the notion of justice as punishment, with serious cases of international corruption resolved with minimal retribution for offending MNEs. Taking a utilitarian ethical perspective, we also evaluate the effect of DPAs on MNEs’ tendency to self-regulate or re-offend. Our conclusion, supported by critical analysis of the juridical literature and case evidence on MNEs’ recidivism, is that DPAs do not foster ethical behavior

Prevention of neurological injuries during mandibular third molar surgery: technical notes

Surgery to the mandibular third molar is common, and injuries to the inferior alveolar nerve and the lingual nerve are well-recognized complications of this procedure. The aim of these technical notes is to describe operative measures for reducing neurological complications during mandibular third molar surgery. The following procedure should be used to prevent damage to the inferior alveolar nerve: a well-designed mucoperiosteal flap, to obtain appropriate access to the surgical area; a conservative ostectomy on the distal and distal-lingual side; tooth sectioning, to facilitate its removal by decreasing the retention zones; tooth dislocation in the path of withdrawal imposed by the curvature of the root apex; and careful socket debridement, when the roots of the extracted tooth are in intimate contact with the mandibular canal. To prevent injury to the lingual nerve, it is important (I) to assess the integrity of the mandibular inner cortex and exclude the presence of fenestration, which could cause the dislocation of the tooth or its fragment into the sublingual or submandibular space; (II) to avoid inappropriate or excessive dislocation proceedings, in order to prevent lingual cortex fracture; (III) to perform horizontal mesial-distal crown sectioning of the lingually inclined tooth; (IV) to protect the lingual flap with a retractor showing the cortical ridge; and (V) to pass the suture not too apically and from the inner side in a buccal-lingual direction in the retromolar are