Laura Catenacci - Academia.edu (original) (raw)
Papers by Laura Catenacci
Pharmaceutics
Berberine (BBR) is known for its antitumor activity and photosensitizer properties in anti-cancer... more Berberine (BBR) is known for its antitumor activity and photosensitizer properties in anti-cancer photodynamic therapy (PDT), and it has previously been favorably assayed against glioblastoma multiforme (GBM)-derived cells. In this work, two BBR hydrophobic salts, dodecyl sulfate (S) and laurate (L), have been encapsulated in PLGA-based nanoparticles (NPs), chitosan-coated by the addition of chitosan oleate in the preparation. NPs were also further functionalized with folic acid. All the BBR-loaded NPs were efficiently internalized into T98G GBM established cells, and internalization increased in the presence of folic acid. However, the highest mitochondrial co-localization percentages were obtained with BBR-S NPs without folic acid content. In the T98G cells, BBR-S NPs appeared to be the most efficient in inducing cytotoxicity events and were therefore selected to assess the effect of photodynamic stimulation (PDT). As a result, PDT potentiated the viability reduction for the BBR-S...
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Pharmaceutics
Tissue repair and regeneration is an interdisciplinary field focusing on developing bioactive sub... more Tissue repair and regeneration is an interdisciplinary field focusing on developing bioactive substitutes aimed at restoring pristine functions of damaged, diseased tissues. Biomaterials, intended as those materials compatible with living tissues after in vivo administration, play a pivotal role in this area and they have been successfully studied and developed for several years. Namely, the researches focus on improving bio-inert biomaterials that well integrate in living tissues with no or minimal tissue response, or bioactive materials that influence biological response, stimulating new tissue re-growth. This review aims to gather and introduce, in the context of Italian scientific community, cutting-edge advancements in biomaterial science applied to tissue repair and regeneration. After introducing tissue repair and regeneration, the review focuses on biodegradable and biocompatible biomaterials such as collagen, polysaccharides, silk proteins, polyesters and their derivatives,...
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Pharmaceutics, 2021
Injuries to the nervous system affect more than one billion people worldwide, and dramatically im... more Injuries to the nervous system affect more than one billion people worldwide, and dramatically impact on the patient’s quality of life. The present work aimed to design and develop a gellan gum (GG)-based composite system for the local delivery of the neuroprotective sigma-1 receptor agonist, 1-[3-(1,1′-biphen)-4-yl] butylpiperidine (RC-33), as a potential tool for the treatment of tissue nervous injuries. The system, consisting of cross-linked electrospun nanofibers embedded in a RC-33-loaded freeze-dried matrix, was designed to bridge the lesion gap, control drug delivery and enhance axonal regrowth. The gradual matrix degradation should ensure the progressive interaction between the inner fibrous mat and the surrounding cellular environment. Nanofibers, prepared by electrospinning polymeric solutions containing GG, two different grades of poly (ethylene oxide) and poloxamer, were cross-linked with calcium ions. GG-based matrices, loaded with different amounts of RC-33, were prepa...
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Pharmaceuticals, 2021
In the last decades, it has been demonstrated that the regenerative therapeutic efficacy of mesen... more In the last decades, it has been demonstrated that the regenerative therapeutic efficacy of mesenchymal stromal cells is primarily due to the secretion of soluble factors and extracellular vesicles, collectively known as secretome. In this context, our work described the preparation and characterization of a freeze-dried secretome (Lyosecretome) from adipose tissue-derived mesenchymal stromal cells for the therapy of equine musculoskeletal disorder. An intraarticular injectable pharmaceutical powder has been formulated, and the technological process has been validated in an authorized facility for veterinary clinical-use medicinal production. Critical parameters for quality control and batch release have been identified regarding (i) physicochemical properties; (ii) extracellular vesicle morphology, size distribution, and surface biomarker; (iii) protein and lipid content; (iv) requirements for injectable pharmaceutical dosage forms such as sterility, bacterial endotoxin, and Mycopl...
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Pharmaceutics, 2021
Oligonucleotide therapeutics such as miRNAs and siRNAs represent a class of molecules developed t... more Oligonucleotide therapeutics such as miRNAs and siRNAs represent a class of molecules developed to modulate gene expression by interfering with ribonucleic acids (RNAs) and protein synthesis. These molecules are characterized by strong instability and easy degradation due to nuclease enzymes. To avoid these drawbacks and ensure efficient delivery to target cells, viral and non-viral vectors are the two main approaches currently employed. Viral vectors are one of the major vehicles in gene therapy; however, the potent immunogenicity and the insertional mutagenesis is a potential issue for the patient. Non-viral vectors, such as polymeric nanocarriers, provide a safer and more efficient delivery of RNA-interfering molecules. The aim of this work is to employ PLGA core nanoparticles shell-coated with chitosan oleate as siRNA carriers. An siRNA targeted on HIV-1, directed against the viral Tat/Rev transcripts was employed as a model. The ionic interaction between the oligonucleotide’s m...
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Cancers, 2021
Surgical resection is the gold standard for the treatment of many kinds of tumor, but its success... more Surgical resection is the gold standard for the treatment of many kinds of tumor, but its success depends on the early diagnosis and the absence of metastases. However, many deep-seated tumors (liver, pancreas, for example) are often unresectable at the time of diagnosis. Chemotherapies and radiotherapies are a second line for cancer treatment. The “enhanced permeability and retention” (EPR) effect is believed to play a fundamental role in the passive uptake of drug-loaded nanocarriers, for example polymeric nanoparticles, in deep-seated tumors. However, criticisms of the EPR effect were recently raised, particularly in advanced human cancers: obstructed blood vessels and suppressed blood flow determine a heterogeneity of the EPR effect, with negative consequences on nanocarrier accumulation, retention, and intratumoral distribution. Therefore, to improve the nanomedicine uptake, there is a strong need for “EPR enhancers”. Electrochemotherapy represents an important tool for the tre...
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Pharmaceutics, 2020
Oxidative stress has a key role in the pathogenesis of neurodegenerative disorders such as Alzhei... more Oxidative stress has a key role in the pathogenesis of neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Huntington’s diseases and can be an important cause of the damages in cerebral ischemia. Oxidative stress arises from high levels of reactive oxygen species (ROS). Consequently, on this rational base, antioxidants (many of natural origin) are proposed as potential drugs to prevent ROS noxious actions because they can protect the target tissues from the oxidative stress. However, the potential of antioxidants is limited, owing to the presence of the blood–brain barrier (BBB), which is difficult to cross with a consequent low bioavailability of the drug into the brain after systemic (intravenous, intraperitoneal, oral) administrations. One strategy to improve the delivery of antioxidants to the brain involves the use of the so-called nose-to-brain route, with the administration of the antioxidant in specific nasal formulations and its passage to the central nervous ...
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Proceedings of The 1st International Electronic Conference on Pharmaceutics, 2020
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Materials, 2020
Collagen, thanks to its biocompatibility, biodegradability and weak antigenicity, is widely used ... more Collagen, thanks to its biocompatibility, biodegradability and weak antigenicity, is widely used in dressings and scaffolds, also as electrospun fibers. Its mechanical stability can be improved by adding polycaprolactone (PCL), a synthetic and biodegradable aliphatic polyester. While previously collagen/PCL combinations were electrospun in solvents such as hexafluoroisopropanol (HFIP) or trifluoroethanol (TFE), more recently literature describes collagen/PCL nanofibers obtained in acidic aqueous solutions. A good morphology of the fibers represents in this case still a challenge, especially for high collagen/PCL ratios. In this work, thanks to preliminary rheological and physicochemical characterization of the solutions and to a Design of Experiments (DOE) approach on process parameters, regular and dimensionally uniform fibers were obtained with collagen/PCL ratios up to 1:2 and 1:1 w/w. Collagen ratio appeared relevant for mechanical strength of dry and hydrated fibers. WAXS and F...
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Pharmaceutics, 2020
Mesenchymal stem/stromal cells (MSCs) are a therapeutic target to promote tissue regeneration, ma... more Mesenchymal stem/stromal cells (MSCs) are a therapeutic target to promote tissue regeneration, mainly when oxidative stress-mediated damage is involved in disease pathogenesis. Here, slow-release silk sericin nanoparticles (SNPs) loaded with natural antioxidant polyphenols were developed to sustain regeneration by tissue-resident MSCs. SNPs were prepared by exploiting a self-assembly method with poloxamer and were loaded with proanthocyanidins (P), quercetin (Q) or epigallocatechin gallate (E). SNPs, with a diameter less than 150 nm, were able to encapsulate both hydrophilic (P and E) and hydrophobic (Q) drugs. A slow and controlled release was obtained from SNPs for all the actives in PBS, while in EtOH, Q and E showed a burst release but P did not. Kinetic models revealed lower diffusion of P than other biomolecules, probably due to the higher steric hindrance of P. The in vitro anti-oxidant, anti-elastase and anti-tyrosinase properties of SNPs were assessed: loading the P and E i...
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Molecules, 2020
The aim of the study was to determine the feasibility of complexation between the antioxidant tra... more The aim of the study was to determine the feasibility of complexation between the antioxidant trans-resveratrol (RSV) and underivatized cyclodextrins (CDs) using a variety of preparative methods, including physical mixing, kneading, microwave irradiation, co-evaporation, and co-precipitation techniques. Products were characterized using differential scanning calorimetry (DSC), simultaneous thermogravimetric/DSC analysis (TGA/DSC), Fourier transform infrared (FT-IR) spectroscopy, and powder X-ray diffraction (PXRD). With α-CD and RSV, sample amorphization was revealed by PXRD and FT-IR, but no definitive inclusion complexation was evident. Similar results were obtained in attempts to complex RSV with β-CD. However, complex formation between γ-CD and RSV was evident from observation of an endo-/exothermic effect appearing in the DSC trace of the product from kneading and was further corroborated by FT-IR and PXRD methods. The latter technique indicated complexation unequivocally as th...
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Polymers, 2018
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Cells, 2018
In this paper, a pilot production process for mesenchymal stem/stromal freeze-dried secretome was... more In this paper, a pilot production process for mesenchymal stem/stromal freeze-dried secretome was performed in a validated good manufacturing practice (GMP)-compliant cell factory. Secretome was purified from culture supernatants by ultrafiltration, added to cryoprotectant, lyophilized and characterized. We obtained a freeze-dried, “ready-off-the-shelf” and free soluble powder containing extracellular vesicles and proteins. In the freeze-dried product, a not-aggregated population of extracellular vesicles was detected by nanoparticle tracking analysis; Fourier transform infrared spectra showed the simultaneous presence of protein and lipids, while differential scanning calorimetry demonstrated that lyophilization process successfully occurred. A proteomic characterization allowed the identification of proteins involved in immune response, response to stress, cytoskeleton and metabolism. Moreover, the product was not cytotoxic up to concentrations of 25 mg/mL (on human fibroblasts, c...
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European journal of medicinal chemistry, Jan 5, 2018
In this manuscript we report on the design, synthesis and evaluation of dual Sigma 1 Receptor (S1... more In this manuscript we report on the design, synthesis and evaluation of dual Sigma 1 Receptor (S1R) modulators/Acetylcholinesterase (AChE) inhibitors endowed with antioxidant and neurotrophic properties, potentially able to counteract neurodegeneration. The compounds based on arylalkylaminoketone scaffold integrate the pharmacophoric elements of RRC-33, a S1R modulator developed by us, donepezil, a well-known AChE inhibitor, and curcumin, a natural antioxidant compound with neuroprotective properties. A small library of compounds was synthesized and preliminary in vitro screening performed. Some compounds showed good S1R binding affinity, selectivity towards S2R and N-Methyl-d-Aspartate (NMDA) receptor, AChE relevant inhibiting activity and are potentially able to bypass the BBB, as predicted by the in silico study. For the hits 10 and 20, the antioxidant profile was assessed in SH-SY5Y human neuroblastoma cell lines by evaluating their protective effect against HO cytotoxicity and ...
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Materials (Basel, Switzerland), Jan 23, 2017
Some natural compounds have recently been widely employed in wound healing applications due to th... more Some natural compounds have recently been widely employed in wound healing applications due to their biological properties. One such compound is sericin, which is produced by, while active polyphenols, polysaccharides and proteins are synthetized byandmicroalgae. Our hypothesis was that sericin, as an optimal bioactive polymeric carrier for microencapsulation process, could also improve the regenerative effect of the microalgae. A solvent-free extraction method and spray drying technique were combined to obtain five formulations, based on algal extracts (and, Chl and Art, respectively) or silk sericin (Ser) or their mixtures (Chl-Ser and Art-Ser). The spray drying was a suitable method to produce microspheres with similar dimensions, characterized by collapsed morphology with a rough surface. Art and Art-Ser showed higher antioxidant properties than other formulations. All microspheres resulted in cytocompatibility on fibroblasts until 1.25 mg/mL and promoted cell migration and the ...
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Beilstein Journal of Organic Chemistry, 2014
The phytoalexin trans-resveratrol, 5-[(1E)-2-(4-hydroxyphenyl)ethenyl]-1,3-benzenediol, is a well... more The phytoalexin trans-resveratrol, 5-[(1E)-2-(4-hydroxyphenyl)ethenyl]-1,3-benzenediol, is a well-known, potent antioxidant having a variety of possible biomedical applications. However, its adverse physicochemical properties (low stability, poor aqueous solubility) limit such applications and its inclusion in cyclodextrins (CDs) has potential for addressing these shortcomings. Here, various methods of the attempted synthesis of inclusion complexes between trans-resveratrol and three methylated cyclodextrins (permethylated α-CD, permethylated β-CD and 2,6-dimethylated β-CD) are described. Isolation of the corresponding crystalline 1:1 inclusion compounds enabled their full structure determination by X-ray analysis for the first time, revealing a variety of guest inclusion modes and unique supramolecular crystal packing motifs. The three crystalline inclusion complexes were also fully characterized by thermal analysis (hot stage microscopy, thermogravimetric analysis and differential...
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Pharmaceutical Development and Technology, 2008
The aim of the present work was to investigate the capability of vancomycin (VCM) to interact wit... more The aim of the present work was to investigate the capability of vancomycin (VCM) to interact with three hydrophobic cyclodextrins (TACD) (triacetyl alpha-, beta-, or gamma cyclodextrin) and the role played by the preparation technique in the formation of interaction products aimed at prolonging drug delivery for site-specific treatment of bone infections. Physical mixtures of VCM with triacetyl alpha-, beta-, or gamma-cyclodextrin in a 1:1 molar ratio were subjected to kneading, coevaporation, and spray drying from aqueous suspensions or hydroacetonic solution. Thermal behavior (TG, DSC), percent drug content (HPLC), and drug release (Franz cell) of VCM from the physical mixtures, and the relevant binary systems obtained by the various complexation methods were evaluated. All binary systems were characterized by having a particle size compatible with parenteral site-specific administration and with drug-loading efficiencies close to 100%, thus indicating the stability of vancomycin toward each and every complexation process. In vitro drug release measurements showed that the preparation technique plays a different role depending on the type of cyclodextrin used. In the kneading process, the binary system containing TAalphaCD is the most efficient in slowing down the VCM release. With the coevaporation technique, the system based on TAbetaCD was most effective in prolonging drug release. None of the triacetyl-cyclodextrins is suitable in prolonging VCM release upon spray drying from aqueous suspensions, because this preparation technique does not determine drug-cyclodextrin interaction. On the other hand, spray drying from hydroacetonic solutions always results in a reduction in drug release, linked to the formation of VCM-TACD interaction products and is particularly pronounced for the VCM-TAgammaCD interaction product. The unique properties of prolonging drug release and maintaining the antimicrobial activity of the native drug render such an interaction product the most promising candidate in the development of delivery systems intended for parenteral site-specific administration of VCM.
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Journal of Thermal Analysis and Calorimetry, 2004
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Journal of Pharmacy and Pharmacology, 2009
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Journal of Pharmaceutical Sciences, 2007
The isolation and physicochemical characterization of four crystalline modifications of brodimopr... more The isolation and physicochemical characterization of four crystalline modifications of brodimoprim (5-[(4-bromo-3,5-dimethoxyphenyl)methyl]-2,4-pyrimidinediamine, hereinafter BMP), a structural analog of trimethoprim (TMP), are reported. These phases include an unsolvated form of BMP, a hemihydrate (BMP 0.5H(2)O), a 1:1 solvate containing isopropanol (BMP C(3)H(7)OH(iso)), and a hemichloroformate (BMP 0.5CHCl(3)). Unsolvated BMP was isolated both by recrystallization from a range of common solvents as well as by thermal decomposition of the above solvates and no evidence for polymorphism was found. PXRD data indicated that the three solvates crystallize in different arrangements. Data from thermal analysis (thermogravimetry (TGA), hot stage microscopy (HSM), differential scanning calorimetry (DSC)) of the solvates containing water and iso-propanol were interpreted on the basis of their single-crystal X-ray structures which revealed that the modes of solvent inclusion in BMP 0.5H(2)O and BMP C(3)H(7)OH(iso) may be described as 'isolated site' and 'lattice channel' type inclusions, respectively.
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Pharmaceutics
Berberine (BBR) is known for its antitumor activity and photosensitizer properties in anti-cancer... more Berberine (BBR) is known for its antitumor activity and photosensitizer properties in anti-cancer photodynamic therapy (PDT), and it has previously been favorably assayed against glioblastoma multiforme (GBM)-derived cells. In this work, two BBR hydrophobic salts, dodecyl sulfate (S) and laurate (L), have been encapsulated in PLGA-based nanoparticles (NPs), chitosan-coated by the addition of chitosan oleate in the preparation. NPs were also further functionalized with folic acid. All the BBR-loaded NPs were efficiently internalized into T98G GBM established cells, and internalization increased in the presence of folic acid. However, the highest mitochondrial co-localization percentages were obtained with BBR-S NPs without folic acid content. In the T98G cells, BBR-S NPs appeared to be the most efficient in inducing cytotoxicity events and were therefore selected to assess the effect of photodynamic stimulation (PDT). As a result, PDT potentiated the viability reduction for the BBR-S...
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Pharmaceutics
Tissue repair and regeneration is an interdisciplinary field focusing on developing bioactive sub... more Tissue repair and regeneration is an interdisciplinary field focusing on developing bioactive substitutes aimed at restoring pristine functions of damaged, diseased tissues. Biomaterials, intended as those materials compatible with living tissues after in vivo administration, play a pivotal role in this area and they have been successfully studied and developed for several years. Namely, the researches focus on improving bio-inert biomaterials that well integrate in living tissues with no or minimal tissue response, or bioactive materials that influence biological response, stimulating new tissue re-growth. This review aims to gather and introduce, in the context of Italian scientific community, cutting-edge advancements in biomaterial science applied to tissue repair and regeneration. After introducing tissue repair and regeneration, the review focuses on biodegradable and biocompatible biomaterials such as collagen, polysaccharides, silk proteins, polyesters and their derivatives,...
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Pharmaceutics, 2021
Injuries to the nervous system affect more than one billion people worldwide, and dramatically im... more Injuries to the nervous system affect more than one billion people worldwide, and dramatically impact on the patient’s quality of life. The present work aimed to design and develop a gellan gum (GG)-based composite system for the local delivery of the neuroprotective sigma-1 receptor agonist, 1-[3-(1,1′-biphen)-4-yl] butylpiperidine (RC-33), as a potential tool for the treatment of tissue nervous injuries. The system, consisting of cross-linked electrospun nanofibers embedded in a RC-33-loaded freeze-dried matrix, was designed to bridge the lesion gap, control drug delivery and enhance axonal regrowth. The gradual matrix degradation should ensure the progressive interaction between the inner fibrous mat and the surrounding cellular environment. Nanofibers, prepared by electrospinning polymeric solutions containing GG, two different grades of poly (ethylene oxide) and poloxamer, were cross-linked with calcium ions. GG-based matrices, loaded with different amounts of RC-33, were prepa...
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Pharmaceuticals, 2021
In the last decades, it has been demonstrated that the regenerative therapeutic efficacy of mesen... more In the last decades, it has been demonstrated that the regenerative therapeutic efficacy of mesenchymal stromal cells is primarily due to the secretion of soluble factors and extracellular vesicles, collectively known as secretome. In this context, our work described the preparation and characterization of a freeze-dried secretome (Lyosecretome) from adipose tissue-derived mesenchymal stromal cells for the therapy of equine musculoskeletal disorder. An intraarticular injectable pharmaceutical powder has been formulated, and the technological process has been validated in an authorized facility for veterinary clinical-use medicinal production. Critical parameters for quality control and batch release have been identified regarding (i) physicochemical properties; (ii) extracellular vesicle morphology, size distribution, and surface biomarker; (iii) protein and lipid content; (iv) requirements for injectable pharmaceutical dosage forms such as sterility, bacterial endotoxin, and Mycopl...
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Pharmaceutics, 2021
Oligonucleotide therapeutics such as miRNAs and siRNAs represent a class of molecules developed t... more Oligonucleotide therapeutics such as miRNAs and siRNAs represent a class of molecules developed to modulate gene expression by interfering with ribonucleic acids (RNAs) and protein synthesis. These molecules are characterized by strong instability and easy degradation due to nuclease enzymes. To avoid these drawbacks and ensure efficient delivery to target cells, viral and non-viral vectors are the two main approaches currently employed. Viral vectors are one of the major vehicles in gene therapy; however, the potent immunogenicity and the insertional mutagenesis is a potential issue for the patient. Non-viral vectors, such as polymeric nanocarriers, provide a safer and more efficient delivery of RNA-interfering molecules. The aim of this work is to employ PLGA core nanoparticles shell-coated with chitosan oleate as siRNA carriers. An siRNA targeted on HIV-1, directed against the viral Tat/Rev transcripts was employed as a model. The ionic interaction between the oligonucleotide’s m...
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Cancers, 2021
Surgical resection is the gold standard for the treatment of many kinds of tumor, but its success... more Surgical resection is the gold standard for the treatment of many kinds of tumor, but its success depends on the early diagnosis and the absence of metastases. However, many deep-seated tumors (liver, pancreas, for example) are often unresectable at the time of diagnosis. Chemotherapies and radiotherapies are a second line for cancer treatment. The “enhanced permeability and retention” (EPR) effect is believed to play a fundamental role in the passive uptake of drug-loaded nanocarriers, for example polymeric nanoparticles, in deep-seated tumors. However, criticisms of the EPR effect were recently raised, particularly in advanced human cancers: obstructed blood vessels and suppressed blood flow determine a heterogeneity of the EPR effect, with negative consequences on nanocarrier accumulation, retention, and intratumoral distribution. Therefore, to improve the nanomedicine uptake, there is a strong need for “EPR enhancers”. Electrochemotherapy represents an important tool for the tre...
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Pharmaceutics, 2020
Oxidative stress has a key role in the pathogenesis of neurodegenerative disorders such as Alzhei... more Oxidative stress has a key role in the pathogenesis of neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Huntington’s diseases and can be an important cause of the damages in cerebral ischemia. Oxidative stress arises from high levels of reactive oxygen species (ROS). Consequently, on this rational base, antioxidants (many of natural origin) are proposed as potential drugs to prevent ROS noxious actions because they can protect the target tissues from the oxidative stress. However, the potential of antioxidants is limited, owing to the presence of the blood–brain barrier (BBB), which is difficult to cross with a consequent low bioavailability of the drug into the brain after systemic (intravenous, intraperitoneal, oral) administrations. One strategy to improve the delivery of antioxidants to the brain involves the use of the so-called nose-to-brain route, with the administration of the antioxidant in specific nasal formulations and its passage to the central nervous ...
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Proceedings of The 1st International Electronic Conference on Pharmaceutics, 2020
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Materials, 2020
Collagen, thanks to its biocompatibility, biodegradability and weak antigenicity, is widely used ... more Collagen, thanks to its biocompatibility, biodegradability and weak antigenicity, is widely used in dressings and scaffolds, also as electrospun fibers. Its mechanical stability can be improved by adding polycaprolactone (PCL), a synthetic and biodegradable aliphatic polyester. While previously collagen/PCL combinations were electrospun in solvents such as hexafluoroisopropanol (HFIP) or trifluoroethanol (TFE), more recently literature describes collagen/PCL nanofibers obtained in acidic aqueous solutions. A good morphology of the fibers represents in this case still a challenge, especially for high collagen/PCL ratios. In this work, thanks to preliminary rheological and physicochemical characterization of the solutions and to a Design of Experiments (DOE) approach on process parameters, regular and dimensionally uniform fibers were obtained with collagen/PCL ratios up to 1:2 and 1:1 w/w. Collagen ratio appeared relevant for mechanical strength of dry and hydrated fibers. WAXS and F...
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Pharmaceutics, 2020
Mesenchymal stem/stromal cells (MSCs) are a therapeutic target to promote tissue regeneration, ma... more Mesenchymal stem/stromal cells (MSCs) are a therapeutic target to promote tissue regeneration, mainly when oxidative stress-mediated damage is involved in disease pathogenesis. Here, slow-release silk sericin nanoparticles (SNPs) loaded with natural antioxidant polyphenols were developed to sustain regeneration by tissue-resident MSCs. SNPs were prepared by exploiting a self-assembly method with poloxamer and were loaded with proanthocyanidins (P), quercetin (Q) or epigallocatechin gallate (E). SNPs, with a diameter less than 150 nm, were able to encapsulate both hydrophilic (P and E) and hydrophobic (Q) drugs. A slow and controlled release was obtained from SNPs for all the actives in PBS, while in EtOH, Q and E showed a burst release but P did not. Kinetic models revealed lower diffusion of P than other biomolecules, probably due to the higher steric hindrance of P. The in vitro anti-oxidant, anti-elastase and anti-tyrosinase properties of SNPs were assessed: loading the P and E i...
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Molecules, 2020
The aim of the study was to determine the feasibility of complexation between the antioxidant tra... more The aim of the study was to determine the feasibility of complexation between the antioxidant trans-resveratrol (RSV) and underivatized cyclodextrins (CDs) using a variety of preparative methods, including physical mixing, kneading, microwave irradiation, co-evaporation, and co-precipitation techniques. Products were characterized using differential scanning calorimetry (DSC), simultaneous thermogravimetric/DSC analysis (TGA/DSC), Fourier transform infrared (FT-IR) spectroscopy, and powder X-ray diffraction (PXRD). With α-CD and RSV, sample amorphization was revealed by PXRD and FT-IR, but no definitive inclusion complexation was evident. Similar results were obtained in attempts to complex RSV with β-CD. However, complex formation between γ-CD and RSV was evident from observation of an endo-/exothermic effect appearing in the DSC trace of the product from kneading and was further corroborated by FT-IR and PXRD methods. The latter technique indicated complexation unequivocally as th...
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Polymers, 2018
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Cells, 2018
In this paper, a pilot production process for mesenchymal stem/stromal freeze-dried secretome was... more In this paper, a pilot production process for mesenchymal stem/stromal freeze-dried secretome was performed in a validated good manufacturing practice (GMP)-compliant cell factory. Secretome was purified from culture supernatants by ultrafiltration, added to cryoprotectant, lyophilized and characterized. We obtained a freeze-dried, “ready-off-the-shelf” and free soluble powder containing extracellular vesicles and proteins. In the freeze-dried product, a not-aggregated population of extracellular vesicles was detected by nanoparticle tracking analysis; Fourier transform infrared spectra showed the simultaneous presence of protein and lipids, while differential scanning calorimetry demonstrated that lyophilization process successfully occurred. A proteomic characterization allowed the identification of proteins involved in immune response, response to stress, cytoskeleton and metabolism. Moreover, the product was not cytotoxic up to concentrations of 25 mg/mL (on human fibroblasts, c...
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European journal of medicinal chemistry, Jan 5, 2018
In this manuscript we report on the design, synthesis and evaluation of dual Sigma 1 Receptor (S1... more In this manuscript we report on the design, synthesis and evaluation of dual Sigma 1 Receptor (S1R) modulators/Acetylcholinesterase (AChE) inhibitors endowed with antioxidant and neurotrophic properties, potentially able to counteract neurodegeneration. The compounds based on arylalkylaminoketone scaffold integrate the pharmacophoric elements of RRC-33, a S1R modulator developed by us, donepezil, a well-known AChE inhibitor, and curcumin, a natural antioxidant compound with neuroprotective properties. A small library of compounds was synthesized and preliminary in vitro screening performed. Some compounds showed good S1R binding affinity, selectivity towards S2R and N-Methyl-d-Aspartate (NMDA) receptor, AChE relevant inhibiting activity and are potentially able to bypass the BBB, as predicted by the in silico study. For the hits 10 and 20, the antioxidant profile was assessed in SH-SY5Y human neuroblastoma cell lines by evaluating their protective effect against HO cytotoxicity and ...
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Materials (Basel, Switzerland), Jan 23, 2017
Some natural compounds have recently been widely employed in wound healing applications due to th... more Some natural compounds have recently been widely employed in wound healing applications due to their biological properties. One such compound is sericin, which is produced by, while active polyphenols, polysaccharides and proteins are synthetized byandmicroalgae. Our hypothesis was that sericin, as an optimal bioactive polymeric carrier for microencapsulation process, could also improve the regenerative effect of the microalgae. A solvent-free extraction method and spray drying technique were combined to obtain five formulations, based on algal extracts (and, Chl and Art, respectively) or silk sericin (Ser) or their mixtures (Chl-Ser and Art-Ser). The spray drying was a suitable method to produce microspheres with similar dimensions, characterized by collapsed morphology with a rough surface. Art and Art-Ser showed higher antioxidant properties than other formulations. All microspheres resulted in cytocompatibility on fibroblasts until 1.25 mg/mL and promoted cell migration and the ...
Bookmarks Related papers MentionsView impact
Beilstein Journal of Organic Chemistry, 2014
The phytoalexin trans-resveratrol, 5-[(1E)-2-(4-hydroxyphenyl)ethenyl]-1,3-benzenediol, is a well... more The phytoalexin trans-resveratrol, 5-[(1E)-2-(4-hydroxyphenyl)ethenyl]-1,3-benzenediol, is a well-known, potent antioxidant having a variety of possible biomedical applications. However, its adverse physicochemical properties (low stability, poor aqueous solubility) limit such applications and its inclusion in cyclodextrins (CDs) has potential for addressing these shortcomings. Here, various methods of the attempted synthesis of inclusion complexes between trans-resveratrol and three methylated cyclodextrins (permethylated α-CD, permethylated β-CD and 2,6-dimethylated β-CD) are described. Isolation of the corresponding crystalline 1:1 inclusion compounds enabled their full structure determination by X-ray analysis for the first time, revealing a variety of guest inclusion modes and unique supramolecular crystal packing motifs. The three crystalline inclusion complexes were also fully characterized by thermal analysis (hot stage microscopy, thermogravimetric analysis and differential...
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Pharmaceutical Development and Technology, 2008
The aim of the present work was to investigate the capability of vancomycin (VCM) to interact wit... more The aim of the present work was to investigate the capability of vancomycin (VCM) to interact with three hydrophobic cyclodextrins (TACD) (triacetyl alpha-, beta-, or gamma cyclodextrin) and the role played by the preparation technique in the formation of interaction products aimed at prolonging drug delivery for site-specific treatment of bone infections. Physical mixtures of VCM with triacetyl alpha-, beta-, or gamma-cyclodextrin in a 1:1 molar ratio were subjected to kneading, coevaporation, and spray drying from aqueous suspensions or hydroacetonic solution. Thermal behavior (TG, DSC), percent drug content (HPLC), and drug release (Franz cell) of VCM from the physical mixtures, and the relevant binary systems obtained by the various complexation methods were evaluated. All binary systems were characterized by having a particle size compatible with parenteral site-specific administration and with drug-loading efficiencies close to 100%, thus indicating the stability of vancomycin toward each and every complexation process. In vitro drug release measurements showed that the preparation technique plays a different role depending on the type of cyclodextrin used. In the kneading process, the binary system containing TAalphaCD is the most efficient in slowing down the VCM release. With the coevaporation technique, the system based on TAbetaCD was most effective in prolonging drug release. None of the triacetyl-cyclodextrins is suitable in prolonging VCM release upon spray drying from aqueous suspensions, because this preparation technique does not determine drug-cyclodextrin interaction. On the other hand, spray drying from hydroacetonic solutions always results in a reduction in drug release, linked to the formation of VCM-TACD interaction products and is particularly pronounced for the VCM-TAgammaCD interaction product. The unique properties of prolonging drug release and maintaining the antimicrobial activity of the native drug render such an interaction product the most promising candidate in the development of delivery systems intended for parenteral site-specific administration of VCM.
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Journal of Thermal Analysis and Calorimetry, 2004
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Journal of Pharmacy and Pharmacology, 2009
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Journal of Pharmaceutical Sciences, 2007
The isolation and physicochemical characterization of four crystalline modifications of brodimopr... more The isolation and physicochemical characterization of four crystalline modifications of brodimoprim (5-[(4-bromo-3,5-dimethoxyphenyl)methyl]-2,4-pyrimidinediamine, hereinafter BMP), a structural analog of trimethoprim (TMP), are reported. These phases include an unsolvated form of BMP, a hemihydrate (BMP 0.5H(2)O), a 1:1 solvate containing isopropanol (BMP C(3)H(7)OH(iso)), and a hemichloroformate (BMP 0.5CHCl(3)). Unsolvated BMP was isolated both by recrystallization from a range of common solvents as well as by thermal decomposition of the above solvates and no evidence for polymorphism was found. PXRD data indicated that the three solvates crystallize in different arrangements. Data from thermal analysis (thermogravimetry (TGA), hot stage microscopy (HSM), differential scanning calorimetry (DSC)) of the solvates containing water and iso-propanol were interpreted on the basis of their single-crystal X-ray structures which revealed that the modes of solvent inclusion in BMP 0.5H(2)O and BMP C(3)H(7)OH(iso) may be described as 'isolated site' and 'lattice channel' type inclusions, respectively.
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