Pycnogenol (PYC) is a concentrate of phenolic compounds derived from French maritime pine; its bi... more Pycnogenol (PYC) is a concentrate of phenolic compounds derived from French maritime pine; its biological activity as antioxidant, anti-inflammatory and antibacterial suggests its use in the treatment of open wounds. A bioadhesive film, loaded with PYC, was prepared by casting, starting with a combination of two biopolymer acqueous solutions: xanthan gum (1% wt/wt) and sodium alginate (1.5% wt/wt), in a 2.5/7.5 (wt/wt) ratio. In both solutions, glycerol (10% wt/wt) was added as plasticizing agent. The film resulted in an adhesive capable to absorb a simulated wound fluid (~ 65% wt/wt within 1 h), therefore suitable for exuding wounds. The mechanical characterization showed that the film is deformable (elastic modulus E = 3.070 ± 0.044 MPa), suggesting adaptability to any type of surface and resistance to mechanical solicitations. PYC is released within 24 h by a sustained mechanism, achieving a maximum concentration of ~ 0.2 mg/mL, that is safe for keratinocytes, as shown by cytotox...
International Journal of Pharma Research & Review, 2016
Purpose: Current available topical formulations containing non-steroidal anti-inflammatory drugs ... more Purpose: Current available topical formulations containing non-steroidal anti-inflammatory drugs (NSAIDs) suffer from inadequate efficacy due to drug limited solubility (class II of Biopharmaceutics Classification System) responsible for the incomplete absorption of the administered dose in the application site. Another problem is represented by inadequate formulation, difficult to be applied by a massage on inflamed and injured skin. However often this practice results painful for the patient as the formulation used has been projected without taking account of this problem. The aim of this research was to develop a new topical formulation able to release and make available to absorption the complete administered dose and to make the application easy and painfree using the anti-inflammatory drug ketoprofen (KET) as model drug. Methods: At first KET was intercalated in two lamellar anionic clays hydrotalcites (HTlcs), MgAl-HTlc-NO3 and ZnAl-HTlc-NO3, obtaining the inorganic-organic h...
The presence of impurities in medicinal products have to be controlled within safety limits from ... more The presence of impurities in medicinal products have to be controlled within safety limits from a pharmaceutical quality perspective. This matter is of special significance for those countries and regions where the directives, guidelines, or legislations, which prescribe the rules for the application of some products is quite selective or incomplete. Clay-based hydrogels are quite an example of this matter since they are topically administered, but, in some regions, they are not subjected to well-defined legal regulations. Since hydrogels establish an intimate contact with the skin, hazardous elements present in the ingredients could potentially be bioavailable and compromise their safety. The elemental composition and mobility of elements present in two hydrogels have been assessed. Sepiolite, palygorskite, and natural spring water were used as ingredients. The release of a particular element mainly depends on its position in the structure of the hydrogels, not only on its concent...
Ketoprofen (KET) represents one of the most common drugs used in the topical treatment of pain an... more Ketoprofen (KET) represents one of the most common drugs used in the topical treatment of pain and inflammations. However, its potential is rather limited due to the very low solubility and photochemical instability. The local administration of KET by conventional products, such as gels, emulgels, creams, and foams, does not guarantee an efficacious and safe treatment because of its low absorption (due to low solubility) and its sensitivity to UV rays. The photodegradation of KET makes many photoproducts responsible for different adverse effects. In the present work, KET was intercalated into the lamellar anionic clay ZnAl-hydrotalcite (ZnAl-HTlc), obtaining the hybrid ZnAl-KET with improved stability to UV rays and water solubility in comparison to the crystalline form (not intercalated KET). The hybrid was then formulated in autoadhesive patches for local pain treatment. The patches were prepared by casting method starting from a hydrogel based on the biocompatible and bioadhesive...
Abstract Rationale: In the diagnostics of neuroendocrine tumors (NETs), scintigraphy and Single P... more Abstract Rationale: In the diagnostics of neuroendocrine tumors (NETs), scintigraphy and Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) with 111Indium-Octreotide occupy a prominent place. The introduction in clinical practice of 68Gallium-labelled somatostatin analogues (DOTA-TOC, DOTA-TATE, DOTA-NOC) for Positron Emission Tomography/Computed Tomography (PET/CT), significantly improved NETs diagnostics due to greater sensitivity and improved lesion detection in addition to better patient convenience and decreased radiation dose. Patient concerns: We report a case of a patient who was diagnosed with a neuroendocrine tumor of the ileocecal valve. Diagnoses: Diagnosis was made by ultrasonography, CT, and colonoscopy. Hystology after surgery was G2 NET of ileo-cecal valve. Restaging was carried out by 111In-Octreotide SPECT/CT and, 1 month later, by 68Ga-DOTATOC PET/CT. 18F-FDG PET/C was also carried out. Interventions: 68Ga-DOTATOC PET/CT showed larger disease that modified disease management from surgery to medical treatment. Outcomes: After an initial improvement in the patient clinical condition, the tumor caused a worsening with the appearance of ascites. Lessons: 68Ga-DOTA-conjugate PET/CT is appropriate in low and intermediate NET (Ki67 index respectively ≤3% and 3%–20%) characterized by better survival and better response after Peptide Receptor Radionuclide Therapy. 18F-FDG is mostly useful in high grade (G3) of disease, so that 68Ga-DOTA-conjugate SUV and 18F-FDG SUV have an opposite trend in relation to the tumor grade. 68Ga-DOTATOC PET/CT changes, as in our case, therapeutic management in about 40% of cases.
The onion non-edible outside layers represent a widely available waste material deriving from its... more The onion non-edible outside layers represent a widely available waste material deriving from its processing and consumption. As onion is a vegetable showing many beneficial properties for human health, a study aiming to evaluate the use of extract deriving from the non-edible outside layers was planned. An eco-friendly extraction method was optimized using a hydroalcoholic solution as solvent. The obtained extract was deeply characterized by in vitro methods and then formulated in autoadhesive, biocompatible and pain-free hydrogel polymeric films. The extract, very soluble in water, showed antioxidant, radical scavenging, antibacterial and anti-inflammatory activities, suggesting a potential dermal application for wounds treatment. In vitro studies showed a sustained release of the extract from the hydrogel polymeric film suitable to reach concentrations necessary for both antibacterial and anti-inflammatory activities. Test performed on human keratinocytes showed that the formulat...
Neuroinflammation is a feature of many classic neurodegenerative diseases. In the healthy brain, ... more Neuroinflammation is a feature of many classic neurodegenerative diseases. In the healthy brain, microglia cells are distributed throughout the brain and are constantly surveilling the central nervous system (CNS). In response to CNS injury, microglia quickly react by secreting a wide array of apoptotic molecules. Virgin olive oil (VOO) is universally recognized as a symbol of the Mediterranean diet. In the current study, using lipopolysaccharide (LPS)-stimulated BV2 microglia, the anti-inflammatory effects of VOO phenolic extracts from Moraiolo cultivar (MVOO-PE) were investigated. The results showed that low concentration of MVOO-PE prevented microglia cell death and attenuated the LPS-induced activation of toll-like receptor 4 (TLR4)/NOD-like receptor pyrin domain-containing-3 (NLRP3) signaling cascade. The levels of TLR4 and NF-kB were diminished, as well as NLRP3 inflammasome and interleukin-1β (IL-1β) production. Cyclooxygenase-2 (COX-2) isoenzyme and ionized calcium binding a...
Abstract Layered double hydroxides (LDHs) find many applications in the pharmaceutical field. Oft... more Abstract Layered double hydroxides (LDHs) find many applications in the pharmaceutical field. Often, the synthetic product requires a suitable grinding procedure before starting any type of manufacturing process. Choosing the appropriate grinding procedure is important; it must reduce the particle size without modifying the LDH's native layered structure and crystal morphology. Using the LDH MgAl-NO3 as model sample, the aim of this paper was to investigate the influence of three common grinding procedures: knife mill, ball mill and jet mill, on particles size, morphology, specific surface area, crystallinity and flow character. Results highlighted that the jet milling procedure is the most appropriate method to induce particle size reduction while maintaining the original MgAl-NO3 features.
Folic acid (FA) is an important source for the prevention of many diseases. However, its use is l... more Folic acid (FA) is an important source for the prevention of many diseases. However, its use is limited because the very low solubility (<10 mg/l particularly in the gastric environment) responsible for the incomplete adsorption of the administered dose. This study proposes a technological strategy to overcome this problem enhancing FA dissolution rate by means of a formulation able to make completely bioavailable the whole administered dose. Folic acid was intercalated in the layered double hydroxides (LDHs) MgAl-LDH and ZnAl-LDH. The obtained inorganic-organic nanostructured hybrids MgAl-LDH-FA and ZnAl-LDH-FA were deeply characterized and used to prepare immediate release tablets presenting very simple compositions. The hybrids, both as simple powders and as tablets, were submitted to in-vitro release studies mimic the gastric environment conducted both in sink and non-sink conditions. Folic acid release from hybrids, as single powders or as tablets, resulted enhanced in both experiments in comparison with crystalline FA. Obtained results showed that FA-LDH nanostructured hybrids are a promising strategy able to enhance the active ingredient dissolution at low pH values representing a promising approach suitable to realize innovative and effective nutraceutical products.
The common practice of Therapeutic Drug Monitoring (TDM) involves the quantification of drug plas... more The common practice of Therapeutic Drug Monitoring (TDM) involves the quantification of drug plasma concentrations at a specific time in a dosing window. Although TDM for antibiotics is not considered mandatory, it may represent a valid tool for clinicians in order to limit antibiotic resistance and avoid therapeutic failures. The aim of our study was to develop and validate High Performance Liquid Chromatography associated to Diode Array Detection (HPLC-DAD) method for contemporary quantification of ten antibiotics in plasma. This method is endowed with a fast analytical procedure that uses the same chromatographic conditions to quantify ceftazidime, ceftriaxone, meropenem, ertapenem, ciprofloxacin, tigecycline, ampicillin, levofloxacin and piperacillin, plus the beta-lactamase inhibitor tazobactam. Method validation was ensured testing selectivity, accuracy, precision, limits of detection and quantification, recovery and stability. The calibration ranges, established accordingly to the expected plasma concentration in patients, showed a coefficient of determination > 0.996 for all compounds. Within and between-days precisions reported a coefficient of variation less than 15 %. Similarly, the accuracy evaluation reported a relative standard deviation < 10 % for each antibiotic. The recovery ranged between 97 and 103 % for all compounds. This method could represent a useful tool for TDM platform of antibiotics.
Pharmacological research : the official journal of the Italian Pharmacological Society, 2003
This paper is the third part of a survey about patient information and the use of patient package... more This paper is the third part of a survey about patient information and the use of patient package leaflet. The aim of this research section is to analyse the role of the pharmacy and the pharmacist in the health-care field. By means of answers of interviewed people, informations were obtained about the purchase of drugs and other products in pharmacy, the consumer requirements, the non-medical products and self-medication channels of information, the patient-physician and patient-pharmacist quality of communication and the role of advertising for drugs and other products sold in pharmacy. From this survey, it emerged that most of the respondents go to pharmacy to purchase drugs exclusively and only a small number of people go to purchase other products. The pharmacist does not play a remarkable role in providing health information to the patient.
Pycnogenol (PYC) is a concentrate of phenolic compounds derived from French maritime pine; its bi... more Pycnogenol (PYC) is a concentrate of phenolic compounds derived from French maritime pine; its biological activity as antioxidant, anti-inflammatory and antibacterial suggests its use in the treatment of open wounds. A bioadhesive film, loaded with PYC, was prepared by casting, starting with a combination of two biopolymer acqueous solutions: xanthan gum (1% wt/wt) and sodium alginate (1.5% wt/wt), in a 2.5/7.5 (wt/wt) ratio. In both solutions, glycerol (10% wt/wt) was added as plasticizing agent. The film resulted in an adhesive capable to absorb a simulated wound fluid (~ 65% wt/wt within 1 h), therefore suitable for exuding wounds. The mechanical characterization showed that the film is deformable (elastic modulus E = 3.070 ± 0.044 MPa), suggesting adaptability to any type of surface and resistance to mechanical solicitations. PYC is released within 24 h by a sustained mechanism, achieving a maximum concentration of ~ 0.2 mg/mL, that is safe for keratinocytes, as shown by cytotox...
International Journal of Pharma Research & Review, 2016
Purpose: Current available topical formulations containing non-steroidal anti-inflammatory drugs ... more Purpose: Current available topical formulations containing non-steroidal anti-inflammatory drugs (NSAIDs) suffer from inadequate efficacy due to drug limited solubility (class II of Biopharmaceutics Classification System) responsible for the incomplete absorption of the administered dose in the application site. Another problem is represented by inadequate formulation, difficult to be applied by a massage on inflamed and injured skin. However often this practice results painful for the patient as the formulation used has been projected without taking account of this problem. The aim of this research was to develop a new topical formulation able to release and make available to absorption the complete administered dose and to make the application easy and painfree using the anti-inflammatory drug ketoprofen (KET) as model drug. Methods: At first KET was intercalated in two lamellar anionic clays hydrotalcites (HTlcs), MgAl-HTlc-NO3 and ZnAl-HTlc-NO3, obtaining the inorganic-organic h...
The presence of impurities in medicinal products have to be controlled within safety limits from ... more The presence of impurities in medicinal products have to be controlled within safety limits from a pharmaceutical quality perspective. This matter is of special significance for those countries and regions where the directives, guidelines, or legislations, which prescribe the rules for the application of some products is quite selective or incomplete. Clay-based hydrogels are quite an example of this matter since they are topically administered, but, in some regions, they are not subjected to well-defined legal regulations. Since hydrogels establish an intimate contact with the skin, hazardous elements present in the ingredients could potentially be bioavailable and compromise their safety. The elemental composition and mobility of elements present in two hydrogels have been assessed. Sepiolite, palygorskite, and natural spring water were used as ingredients. The release of a particular element mainly depends on its position in the structure of the hydrogels, not only on its concent...
Ketoprofen (KET) represents one of the most common drugs used in the topical treatment of pain an... more Ketoprofen (KET) represents one of the most common drugs used in the topical treatment of pain and inflammations. However, its potential is rather limited due to the very low solubility and photochemical instability. The local administration of KET by conventional products, such as gels, emulgels, creams, and foams, does not guarantee an efficacious and safe treatment because of its low absorption (due to low solubility) and its sensitivity to UV rays. The photodegradation of KET makes many photoproducts responsible for different adverse effects. In the present work, KET was intercalated into the lamellar anionic clay ZnAl-hydrotalcite (ZnAl-HTlc), obtaining the hybrid ZnAl-KET with improved stability to UV rays and water solubility in comparison to the crystalline form (not intercalated KET). The hybrid was then formulated in autoadhesive patches for local pain treatment. The patches were prepared by casting method starting from a hydrogel based on the biocompatible and bioadhesive...
Abstract Rationale: In the diagnostics of neuroendocrine tumors (NETs), scintigraphy and Single P... more Abstract Rationale: In the diagnostics of neuroendocrine tumors (NETs), scintigraphy and Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) with 111Indium-Octreotide occupy a prominent place. The introduction in clinical practice of 68Gallium-labelled somatostatin analogues (DOTA-TOC, DOTA-TATE, DOTA-NOC) for Positron Emission Tomography/Computed Tomography (PET/CT), significantly improved NETs diagnostics due to greater sensitivity and improved lesion detection in addition to better patient convenience and decreased radiation dose. Patient concerns: We report a case of a patient who was diagnosed with a neuroendocrine tumor of the ileocecal valve. Diagnoses: Diagnosis was made by ultrasonography, CT, and colonoscopy. Hystology after surgery was G2 NET of ileo-cecal valve. Restaging was carried out by 111In-Octreotide SPECT/CT and, 1 month later, by 68Ga-DOTATOC PET/CT. 18F-FDG PET/C was also carried out. Interventions: 68Ga-DOTATOC PET/CT showed larger disease that modified disease management from surgery to medical treatment. Outcomes: After an initial improvement in the patient clinical condition, the tumor caused a worsening with the appearance of ascites. Lessons: 68Ga-DOTA-conjugate PET/CT is appropriate in low and intermediate NET (Ki67 index respectively ≤3% and 3%–20%) characterized by better survival and better response after Peptide Receptor Radionuclide Therapy. 18F-FDG is mostly useful in high grade (G3) of disease, so that 68Ga-DOTA-conjugate SUV and 18F-FDG SUV have an opposite trend in relation to the tumor grade. 68Ga-DOTATOC PET/CT changes, as in our case, therapeutic management in about 40% of cases.
The onion non-edible outside layers represent a widely available waste material deriving from its... more The onion non-edible outside layers represent a widely available waste material deriving from its processing and consumption. As onion is a vegetable showing many beneficial properties for human health, a study aiming to evaluate the use of extract deriving from the non-edible outside layers was planned. An eco-friendly extraction method was optimized using a hydroalcoholic solution as solvent. The obtained extract was deeply characterized by in vitro methods and then formulated in autoadhesive, biocompatible and pain-free hydrogel polymeric films. The extract, very soluble in water, showed antioxidant, radical scavenging, antibacterial and anti-inflammatory activities, suggesting a potential dermal application for wounds treatment. In vitro studies showed a sustained release of the extract from the hydrogel polymeric film suitable to reach concentrations necessary for both antibacterial and anti-inflammatory activities. Test performed on human keratinocytes showed that the formulat...
Neuroinflammation is a feature of many classic neurodegenerative diseases. In the healthy brain, ... more Neuroinflammation is a feature of many classic neurodegenerative diseases. In the healthy brain, microglia cells are distributed throughout the brain and are constantly surveilling the central nervous system (CNS). In response to CNS injury, microglia quickly react by secreting a wide array of apoptotic molecules. Virgin olive oil (VOO) is universally recognized as a symbol of the Mediterranean diet. In the current study, using lipopolysaccharide (LPS)-stimulated BV2 microglia, the anti-inflammatory effects of VOO phenolic extracts from Moraiolo cultivar (MVOO-PE) were investigated. The results showed that low concentration of MVOO-PE prevented microglia cell death and attenuated the LPS-induced activation of toll-like receptor 4 (TLR4)/NOD-like receptor pyrin domain-containing-3 (NLRP3) signaling cascade. The levels of TLR4 and NF-kB were diminished, as well as NLRP3 inflammasome and interleukin-1β (IL-1β) production. Cyclooxygenase-2 (COX-2) isoenzyme and ionized calcium binding a...
Abstract Layered double hydroxides (LDHs) find many applications in the pharmaceutical field. Oft... more Abstract Layered double hydroxides (LDHs) find many applications in the pharmaceutical field. Often, the synthetic product requires a suitable grinding procedure before starting any type of manufacturing process. Choosing the appropriate grinding procedure is important; it must reduce the particle size without modifying the LDH's native layered structure and crystal morphology. Using the LDH MgAl-NO3 as model sample, the aim of this paper was to investigate the influence of three common grinding procedures: knife mill, ball mill and jet mill, on particles size, morphology, specific surface area, crystallinity and flow character. Results highlighted that the jet milling procedure is the most appropriate method to induce particle size reduction while maintaining the original MgAl-NO3 features.
Folic acid (FA) is an important source for the prevention of many diseases. However, its use is l... more Folic acid (FA) is an important source for the prevention of many diseases. However, its use is limited because the very low solubility (&amp;amp;amp;amp;amp;amp;lt;10 mg/l particularly in the gastric environment) responsible for the incomplete adsorption of the administered dose. This study proposes a technological strategy to overcome this problem enhancing FA dissolution rate by means of a formulation able to make completely bioavailable the whole administered dose. Folic acid was intercalated in the layered double hydroxides (LDHs) MgAl-LDH and ZnAl-LDH. The obtained inorganic-organic nanostructured hybrids MgAl-LDH-FA and ZnAl-LDH-FA were deeply characterized and used to prepare immediate release tablets presenting very simple compositions. The hybrids, both as simple powders and as tablets, were submitted to in-vitro release studies mimic the gastric environment conducted both in sink and non-sink conditions. Folic acid release from hybrids, as single powders or as tablets, resulted enhanced in both experiments in comparison with crystalline FA. Obtained results showed that FA-LDH nanostructured hybrids are a promising strategy able to enhance the active ingredient dissolution at low pH values representing a promising approach suitable to realize innovative and effective nutraceutical products.
The common practice of Therapeutic Drug Monitoring (TDM) involves the quantification of drug plas... more The common practice of Therapeutic Drug Monitoring (TDM) involves the quantification of drug plasma concentrations at a specific time in a dosing window. Although TDM for antibiotics is not considered mandatory, it may represent a valid tool for clinicians in order to limit antibiotic resistance and avoid therapeutic failures. The aim of our study was to develop and validate High Performance Liquid Chromatography associated to Diode Array Detection (HPLC-DAD) method for contemporary quantification of ten antibiotics in plasma. This method is endowed with a fast analytical procedure that uses the same chromatographic conditions to quantify ceftazidime, ceftriaxone, meropenem, ertapenem, ciprofloxacin, tigecycline, ampicillin, levofloxacin and piperacillin, plus the beta-lactamase inhibitor tazobactam. Method validation was ensured testing selectivity, accuracy, precision, limits of detection and quantification, recovery and stability. The calibration ranges, established accordingly to the expected plasma concentration in patients, showed a coefficient of determination > 0.996 for all compounds. Within and between-days precisions reported a coefficient of variation less than 15 %. Similarly, the accuracy evaluation reported a relative standard deviation < 10 % for each antibiotic. The recovery ranged between 97 and 103 % for all compounds. This method could represent a useful tool for TDM platform of antibiotics.
Pharmacological research : the official journal of the Italian Pharmacological Society, 2003
This paper is the third part of a survey about patient information and the use of patient package... more This paper is the third part of a survey about patient information and the use of patient package leaflet. The aim of this research section is to analyse the role of the pharmacy and the pharmacist in the health-care field. By means of answers of interviewed people, informations were obtained about the purchase of drugs and other products in pharmacy, the consumer requirements, the non-medical products and self-medication channels of information, the patient-physician and patient-pharmacist quality of communication and the role of advertising for drugs and other products sold in pharmacy. From this survey, it emerged that most of the respondents go to pharmacy to purchase drugs exclusively and only a small number of people go to purchase other products. The pharmacist does not play a remarkable role in providing health information to the patient.
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