Drug Carriers: A Review on the Most Used Mathematical Models for Drug Release

Carriers are protective transporters of drugs to target cells, facilitating therapy under each points of view, such as fast healing, reducing infective phenomena, and curing illnesses while avoiding side effects. Over the last 60 years, several scientists have studied drug carrier properties, trying to adapt them to the release environment. Drug/Carrier interaction phenomena have been deeply studied, and the release kinetics have been modeled according to the occurring phenomena involved in the system. It is not easy to define models’ advantages and disadvantages, since each of them may fit in a specific situation, considering material interactions, diffusion and erosion phenomena, and, no less important, the behavior of receiving medium. This work represents a critical review on main mathematical models concerning their dependency on physical, chemical, empirical, or semi-empirical variables. A quantitative representation of release profiles has been shown for the most representative models. A final critical comment on the applicability of these models has been presented at the end. A mathematical approach to this topic may help students and researchers approach the wide panorama of models that exist in literature and have been optimized over time. This models list could be of practical inspiration for the development of researchers’ own new models or for the application of proper modifications, with the introduction of new variable dependency

Optimization of a supercritical assisted process for the production of liposomes for industrial applications

2017 - 2018Liposomes are spherical vesicles made of a double lipidic layer that surrounds an inner aqueous core. Several methods for the preparation of liposomes have been developed in the last decades. However, these methods present drawbacks, such as low reproducibility, batch operations, low encapsulation efficiency of hydrophilic compounds, a difficult control of liposome size distribution and high solvent residue, hindering the real industrial potential of these drug delivery systems. Supercritical fluid (SCF) technologies have been proposed to overcome several limitations of conventional processes for the production of micronized particles carriers, coprecipitates and nanocomposite polymeric structures. Recently, some techniques based on the use of supercritical carbon dioxide have been proposed also for liposome production. However, these methods have still some limitations related to the control of liposome dimension and size distribution and also show very low encapsulation efficiency of hydrophilic drug. The major limitation of these processes, both conventional and supercritical, derives from the hydration step of the lipid layer. Indeed, during this step, only a part of the water used for hydration is actually entrapped into liposomes, resulting in a low overall encapsulation efficiency. Therefore, the objective of this Ph.D. thesis is to develop a novel technology assisted by supercritical carbon dioxide for the production of liposomes of controlled dimensions. The proposed technique was called Supercritical assisted Liposome formation (SuperLip); in this process, first water droplets are produced; then, they are rapidly covered by phospholipids... [edited by Author]XXXI cicl

High Efficiency and New Potential of RSLDE: A Green Technique for the Extraction of Bioactive Molecules from Not Completely Exhausted Plant Biomass and Organic Industrial Processing Waste

A product is characterized by low environmental impact if, during the whole process (from extraction of raw materials from solid natural matter to disposal), its negative contribution to environment modification is significantly reduced or eliminated. According to circular economy, it is important to take into consideration other aspects, such as the possibility to improve the efficiency of extraction process by modifying the principle on which it is based and allowing the recovery of not completely exhausted waste, obtaining other active ingredients, and favoring the recycling of normally eliminated materials. The purpose of this work was to propose more efficient and greener alternatives to conventional solid–liquid extraction processes. Major features are the rapidity of the process, extraction at room temperature and high yields. Rapid Solid–Liquid Dynamic Extraction (RSLDE) represents an innovative solid–liquid extraction technology that allows the solid matrices containing extractable substances in an organic or inorganic solvent and their mixtures to be exhausted in shorter time than current techniques. The principle at the basis of this novel process consists of the generation of a negative pressure gradient between the inside and the outside of the solid matrix, which induces the extraction of compounds not chemically linked to the solid matter, being insoluble in the extractant liquid. Therefore, this work focuses on how RSLDE can potentially bring several improvements in the field of solid–liquid extraction, especially for industrial applications

Comparison Process of Blood Heavy Metals Absorption Linked to Measured Air Quality Data in Areas with High and Low Environmental Impact

Air pollution is a problem shared by the entire world population, and researchers have highlighted its adverse effects on human health in recent years. The object of this paper was the relationship between the pollutants’ concentrations measured in the air and the quantity of pollutant itself inhaled by the human body. The area chosen for the study has a high environmental impact given the significant presence on the territory of polluting activities. The Acerra area (HI) has a waste-to-energy plant and numerous industries to which polluting emissions are attributed. This area has always been the subject of study as the numbers of cancer patients are high. A survey on male patients to evaluate the heavy metals concentrations in the blood was conducted in the two areas and then linked to its values aero-dispersed. Using the air quality data measured by the monitoring networks in two zones, one with high environmental impact (HI) and one with low environmental impact (LI), the chronicle daily intake (CDI) of pollutants inhaled by a single person was calculated. The pollutants considered in this study are PM10 and four heavy metals (As, Cd, Ni, Pb) constituting the typical particulates of the areas concerned. The CDI values calculated for the two zones are significantly higher in the HI zone following the seasonal pollution trend

Operating Parameters Optimization for the Production of Liposomes Loaded with Antibodies Using a Supercritical Fluid-Assisted Process

Encapsulation of antibodies represents a significant advance to protect and deliver these therapeutics in a controlled manner, increasing the stability requested to cover the temporal gap between particle production and their administration. Furthermore, using encapsulation, extracellular, cell surface, and intracellular targets can be reached. This work examines the feasibility of encapsulating mouse IgG isotype control antibodies within phosphatidylcholine-based liposomes using a supercritical fluid-based process called SuperLip (Supercritical-assisted Liposome formation). This process allows a continuous production of both nano- and micrometric liposomes with high encapsulation efficiency working under mild operative conditions. The effect of some operative parameters has been studied on liposome mean diameter, particle size distribution, and antibody entrapment efficiency, comparing these data with those collected working with liposomes obtained by the thin-layer hydration technique. In particular, the effect of water flow rate and of the antibody loading were studied. Antibody-loaded liposomes with mean diameters in the range between 205 and 501 nm have been obtained by using a supercritical fluid-assisted process. High entrapment efficiencies up to 94% have been calculated

Efficacy and durability of multifactorial intervention on mortality and MACEs:a randomized clinical trial in type-2 diabetic kidney disease

Background: Multiple modifiable risk factors for late complications in patients with diabetic kidney disease (DKD), including hyperglycemia, hypertension and dyslipidemia, increase the risk of a poor outcome. DKD is associated with a very high cardiovascular risk, which requires simultaneous treatment of these risk factors by implementing an intensified multifactorial treatment approach. However, the efficacy of a multifactorial intervention on major fatal/non-fatal cardiovascular events (MACEs) in DKD patients has been poorly investigated. Methods: Nephropathy in Diabetes type 2 (NID-2) study is a multicentre, cluster-randomized, open-label clinical trial enrolling 395 DKD patients with albuminuria, diabetic retinopathy (DR) and negative history of CV events in 14 Italian diabetology clinics. Centres were randomly assigned to either Standard-of-Care (SoC) (n = 188) or multifactorial intensive therapy (MT, n = 207) of main cardiovascular risk factors (blood pressure 40/50 mg/dL for men/women and < 175 mg/dL, respectively). Primary endpoint was MACEs occurrence by end of follow-up phase. Secondary endpoints included single components of primary endpoint and all-cause death. Results: At the end of intervention period (median 3.84 and 3.40 years in MT and SoC group, respectively), targets achievement was significantly higher in MT. During 13.0 years (IQR 12.4–13.3) of follow-up, 262 MACEs were recorded (116 in MT vs. 146 in SoC). The adjusted Cox shared-frailty model demonstrated 53% lower risk of MACEs in MT arm (adjusted HR 0.47, 95%CI 0.30–0.74, P = 0.001). Similarly, all-cause death risk was 47% lower (adjusted HR 0.53, 95%CI 0.29–0.93, P = 0.027). Conclusion: MT induces a remarkable benefit on the risk of MACEs and mortality in high-risk DKD patients. Clinical Trial Registration ClinicalTrials.gov number, NCT00535925. https://clinicaltrials.gov/ct2/show/NCT0053592

Drug Carriers: A Review on the Most Used Mathematical Models for Drug Release

Carriers are protective transporters of drugs to target cells, facilitating therapy under each points of view, such as fast healing, reducing infective phenomena, and curing illnesses while avoiding side effects. Over the last 60 years, several scientists have studied drug carrier properties, trying to adapt them to the release environment. Drug/Carrier interaction phenomena have been deeply studied, and the release kinetics have been modeled according to the occurring phenomena involved in the system. It is not easy to define models&rsquo; advantages and disadvantages, since each of them may fit in a specific situation, considering material interactions, diffusion and erosion phenomena, and, no less important, the behavior of receiving medium. This work represents a critical review on main mathematical models concerning their dependency on physical, chemical, empirical, or semi-empirical variables. A quantitative representation of release profiles has been shown for the most representative models. A final critical comment on the applicability of these models has been presented at the end. A mathematical approach to this topic may help students and researchers approach the wide panorama of models that exist in literature and have been optimized over time. This models list could be of practical inspiration for the development of researchers&rsquo; own new models or for the application of proper modifications, with the introduction of new variable dependency

Discrete and Continuous Glucose Monitoring Systems: The Point of View of a Patient Affected by Type-1 Diabetes

This work represents the point of view of a diabetic patient with an indirect experience in this specific field of research. As a chemical engineer and researcher in drug carrier production, he has always approached type-1 diabetes (T1D) in a scientific manner. Therefore, this work represents a description of almost 20 years of this illness treatment using a multi-injection insulin system, compared with the experience acquired with a newly adopted micro-infusion system, allowing automatized insulin administration. The use of the continuous system reduced significantly the Hb1Ac average values, from 8.8% to 6.6%, in less than 2 years. Moreover, a full 24 h control guaranteed the almost total elimination of the hypoglycemia risk, thanks to the automated control system, that can stop insulin administration in order to prevent critical situations. It is also important to note that the point of view underlined in this work does not presume to be that of a doctor or of a researcher who works closely in the field of medicine or diabetology. However, the author wants to highlight that doctors could try to educate patients to a scientific approach to treat illnesses correctly. The author experienced the very common difficulties related to the use of insulin with multi-injection administration for many years; then, he was proposed to start treatment with the automated pump mechanism. In this work, the author provides comments on the physical and psychological advantages and disadvantages of both insulin release systems, in order to define their impact on a patient&rsquo;s daily life. This work may also represent a vademecum for patients during the beginning of diabetes treatment, helped by the constant support and advice of a medical doctor

Sustainability Indicators for Materials and Processes

The concept of sustainability is nowadays employed to compare manufacturing processes or to define the correct path for material selection. Sometimes, this concept is only partially defined, including just low costs, profit maximization and/or CO2 emission reduction. Actually, a process or material can be defined as sustainable only if an objective function related to the economic, environmental and social impacts is simultaneously maximized. To this aim, it is necessary to define appropriate and specific sustainability indicators (i.e., values related to the economic, social and environmental aspects of a process or material under analysis). These indicators come about from simple calculations, and they are defined in terms of percentages and represented and compared using radar diagrams. Then, a process or specific material is identified by an objective function (i.e., the area included by the polygon that links the scores reported on the diagram). The scope of this representation of data is to individuate the major weaknesses of the process/material, proposing methods of optimization and trying to maximize the objective function in the retrieved diagram. This work aims to propose a general and simple method to calculate sustainability indicators on the basis of specific definitions related to a given process/material. To highlight the potential of this calculation and comparison instrument, two case studies are proposed: the first aims at comparing processes for the production of energy, while the second aims at driving the choice of manufacturing material. The selected indicators and adopted algorithm allowed for the identification of hydroelectric and eolic as the most sustainable processes for energy production; for materials, the results strictly depended on the assumptions made regarding favorable mechanical properties