Franca Ferrari | University of Pavia (original) (raw)

Papers by Franca Ferrari

Research paper thumbnail of An In Situ Gelling System for the Local Treatment of Inflammatory Bowel Disease (IBD). The Loading of Maqui (Aristotelia Chilensis) Berry Extract as an Antioxidant and Anti-Inflammatory Agent

Pharmaceutics, 2019

The aim of the present work was the development of an innovative in situ gelling system, to be ap... more The aim of the present work was the development of an innovative in situ gelling system, to be applied on the mucosa of the distal colon via rectal route. The system consisted of three polymers having different functions: gellan (GG), able to jellify in presence of ions; methylcellulose (MC), a thermosensitive polymer with a gelation temperature close to 50 °C; and hydroxypropylcellulose (HPC), a mucoadhesive polymer. The three polymers were able to act synergistically, increasing the permanence of the vehicle on the mucosa and forming a protective gel layer. A DoE approach, “simplex centroid mixture design,” was used to identify the optimal quantitative composition of the vehicle. The response variables considered were: vehicle viscosity at room temperature; increase in vehicle viscosity on increasing temperature (from room to physiological value) and upon dilution with simulated colonic fluid (SCF); and viscoelastic behavior, thixotropic area, and mucoadhesion properties of the ge...

Research paper thumbnail of A Composite Nanosystem as a Potential Tool for the Local Treatment of Glioblastoma: Chitosan-Coated Solid Lipid Nanoparticles Embedded in Electrospun Nanofibers

Polymers

Glioblastoma multiforme (GBM) is one of the most prevalent and aggressive brain tumors for which ... more Glioblastoma multiforme (GBM) is one of the most prevalent and aggressive brain tumors for which there is currently no cure. A novel composite nanosystem (CN), consisting of chitosan-coated Solid Lipid Nanoparticles (c-SLN) embedded in O-carboxymethyl chitosan (O-CMCS)-containing nanofibers (NFs), was proposed as a potential tool for the local delivery of lipophilic anti-proliferative drugs. Coacervation was selected as a solvent-free method for the preparation of stearic acid (SA) and behenic acid (BA)-based SLN (SA-SLN and BA-SLN respectively). BA-SLN, containing 0.75% w/w BA sodium salt and 3% w/w poly(vinyl alcohol) (PVA), were selected for the prosecution of the work since they are characterized by the lowest size functional to their subsequent coating and incorporation in nanofibers. BA-SLN were coated with chitosan (CS) by means of a two-step coating method based on the physical absorption of positively charged CS chains on the SLN negative surface. Nile Red (NR), chosen as t...

Research paper thumbnail of Biomaterials for Soft Tissue Repair and Regeneration: A Focus on Italian Research in the Field

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,...

Research paper thumbnail of Inorganic Nanomaterials in Tissue Engineering

Pharmaceutics

In recent decades, the demand for replacement of damaged or broken tissues has increased; this po... more In recent decades, the demand for replacement of damaged or broken tissues has increased; this poses the attention on problems related to low donor availability. For this reason, researchers focused their attention on the field of tissue engineering, which allows the development of scaffolds able to mimic the tissues’ extracellular matrix. However, tissue replacement and regeneration are complex since scaffolds need to guarantee an adequate hierarchical structured morphology as well as adequate mechanical, chemical, and physical properties to stand the stresses and enhance the new tissue formation. For this purpose, the use of inorganic materials as fillers for the scaffolds has gained great interest in tissue engineering applications, due to their wide range of physicochemical properties as well as their capability to induce biological responses. However, some issues still need to be faced to improve their efficacy. This review focuses on the description of the most effective inorg...

Research paper thumbnail of Smart Device for Biologically Enhanced Functional Regeneration of Osteo–Tendon Interface

Pharmaceutics

The spontaneous healing of a tendon laceration results in the formation of scar tissue, which has... more The spontaneous healing of a tendon laceration results in the formation of scar tissue, which has lower functionality than the original tissue. Moreover, chronic non-healing tendon injuries frequently require surgical treatment. Several types of scaffolds have been developed using the tissue engineering approach, to complement surgical procedures and to enhance the healing process at the injured site. In this work, an electrospun hybrid tubular scaffold was designed to mimic tissue fibrous arrangement and extracellular matrix (ECM) composition, and to be extemporaneously loaded into the inner cavity with human platelet lysate (PL), with the aim of leading to complete post-surgery functional regeneration of the tissue for functional regeneration of the osteo–tendon interface. For this purpose, pullulan (P)/chitosan (CH) based polymer solutions were enriched with hydroxyapatite nanoparticles (HP) and electrospun. The nanofibers were collected vertically along the length of the scaffol...

Research paper thumbnail of Gellan-Based Composite System as a Potential Tool for the Treatment of Nervous Tissue Injuries: Cross-Linked Electrospun Nanofibers Embedded in a RC-33-Loaded Freeze-Dried Matrix

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...

Research paper thumbnail of Development of polyphenol loaded PLGA nanoparticles coated with chitosan oleate

Research paper thumbnail of Nanotechnology-Based Medical Devices for the Treatment of Chronic Skin Lesions: From Research to the Clinic

Pharmaceutics, 2020

Chronic wounds, such as pressure ulcers, diabetic ulcers, venous ulcers and arterial insufficienc... more Chronic wounds, such as pressure ulcers, diabetic ulcers, venous ulcers and arterial insufficiency ulcers, are lesions that fail to proceed through the normal healing process within a period of 12 weeks. The treatment of skin chronic wounds still represents a great challenge. Wound medical devices (MDs) range from conventional and advanced dressings, up to skin grafts, but none of these are generally recognized as a gold standard. Based on recent developments, this paper reviews nanotechnology-based medical devices intended as skin substitutes. In particular, nanofibrous scaffolds are promising platforms for wound healing, especially due to their similarity to the extracellular matrix (ECM) and their capability to promote cell adhesion and proliferation, and to restore skin integrity, when grafted into the wound site. Nanotechnology-based scaffolds are emphasized here. The discussion will be focused on the definition of critical quality attributes (chemical and physical characteriza...

Research paper thumbnail of Stabilization of lemongrass oil nanoemulsions by an ionic amphiphilic derivative of chitosan

Research paper thumbnail of Caratterizzazione del complesso di interazione chitosano-mucina mediante misure viscosimetriche e torbidimetriche

Research paper thumbnail of Water transmission properties and hydration induced modification of hydrocolloid dressings

Research paper thumbnail of In situ Gelling Films loaded with a Carvacrol/Palygorskite hybrid for the treatment of infected skin ulcer

Research paper thumbnail of Relazioni fra forza di disgregazione e penetrazione di acqua nelle compresse: valutazione delle proprietà disgreganti

Chimica Oggi-chemistry Today, 1986

Research paper thumbnail of Effects of Particle Size, Surface Nature and Crystal Type on Dissolution Rate

Particles and Nanoparticles in Pharmaceutical Products, 2018

Solid drug delivery systems are crucial formulations for the oral route. In such systems, particl... more Solid drug delivery systems are crucial formulations for the oral route. In such systems, particle size and polymorphism have a strong impact on drug dissolution and on drug absorption. Starting from the role of particle size in dissolution rate, the Noyes-Whitney equation, the modified form by Nernst-Brunner and the cube root equation are here described. According to these equations diffusion of a solute through a boundary layer around the particles is the rate limiting step for both drug dissolution and absorption and, thus, depends on the specific (external) surface area of the particles, the diffusion coefficient of the dissolved drug, the thickness of the boundary layer and the drug solubility. In relation to this, good wetting of the particle surface by the surrounding liquid and adequate particle dispersion play an essential role. Information from dissolution rates suggests that the thickness of the boundary layer is constant for larger particle sizes, but dependent upon size for smaller particles. Given the larger surface area of smaller particles, the attention has been directed to nanosystems and on their relevance to the bioavailability of poorly soluble drugs. A second advantage of such drug systems is that solubility increases on decreasing particle size, according to the Freundlich–Ostwald equation. The impact of polymorphism, pseudopolymorphism and amorphous form on drug dissolution and bioavailability is also described. Since dissolution and absorption are closely related, the effect of particle size and polymorphism on drug absorption is described. Moreover, regulatory implications of particle size and polymorphism are reviewed.

Research paper thumbnail of Halloysite- and Montmorillonite-Loaded Scaffolds as Enhancers of Chronic Wound Healing

Pharmaceutics, 2020

The increase in life expectancy and the increasing prevalence of diabetic disease and venous insu... more The increase in life expectancy and the increasing prevalence of diabetic disease and venous insufficiency lead to the increase of chronic wounds. The prevalence of ulcers ranges from 1% in the adult population to 3–5% in the over 65 years population, with 3–5.5% of the total healthcare expenditure, as recently estimated. The aim of this work was the design and the development of electrospun scaffolds, entirely based on biopolymers, loaded with montmorillonite (MMT) or halloysite (HNT) and intended for skin reparation and regeneration, as a 3D substrate mimicking the dermal ECM. The scaffolds were manufactured by means of electrospinning and were characterized for their chemico-physical and preclinical properties. The scaffolds proved to possess the capability to enhance fibroblast cells attachment and proliferation with negligible proinflammatory activity. The capability to facilitate the cell adhesion is probably due to their unique 3D structure which are assisting cell homing and...

Research paper thumbnail of Chitosan/Glycosaminoglycan Scaffolds: The Role of Silver Nanoparticles to Control Microbial Infections in Wound Healing

Polymers, 2019

Cutaneous wounds represent a major issue in medical care, with approximately 300 million chronic ... more Cutaneous wounds represent a major issue in medical care, with approximately 300 million chronic and 100 million traumatic wound patients worldwide, and microbial infections slow the healing process. The aim of this work was to develop electrospun scaffolds loaded with silver nanoparticles (AgNPs) to enhance cutaneous healing, preventing wound infections. AgNPs were directly added to polymeric blends based on chitosan (CH) and pullulan (PUL) with hyaluronic acid (HA) or chondroitin sulfate (CS) to be electrospun obtaining nanofibrous scaffolds. Moreover, a scaffold based on CH and PUL and loaded with AgNPs was prepared as a comparison. The scaffolds were characterized by chemico–physical properties, enzymatic degradation, biocompatibility, and antimicrobial properties. All the scaffolds were based on nanofibers (diameters about 500 nm) and the presence of AgNPs was evidenced by TEM and did not modify their morphology. The scaffold degradation was proven by means of lysozyme. Moreove...

Research paper thumbnail of The role of chitosan as coating material for nanostructured lipid carriers for skin delivery of fucoxanthin

International Journal of Pharmaceutics, 2019

Fucoxanthin (FUCO) is a marine carotenoid characterized by antiproliferative properties against h... more Fucoxanthin (FUCO) is a marine carotenoid characterized by antiproliferative properties against hyperproliferative cells. The aim of this work was to design and develop nanostructured lipidic carriers (NLCs) based on bacuri butter and tucumã oil and loaded with FUCO, intended for skin application to prevent skin hyperproliferative diseases and in particular psoriasis. The presence of FUCO should control the hyperproliferation of skin diseased cells and the lipids forming the NLC core, rich in antioxidants and characterized by wound healing properties, should favor the restoring of skin integrity. NLCs were coated with chitosan (CS) to improve their biopharmaceutical properties (bio/mucoadhesion and wound healing) and to combine the advantages of lipidic nanoparticles with the biological properties of CS. Chitosan coated and non-coated NLC were prepared by means of high shear homogenization and characterized for chemico-physical and biopharmaceutical properties (in vitro biocompatibility and cell uptake towards normal dermal human fibroblasts). Moreover, the pharmacological activity of FUCO loaded in NLCs was assessed in psoriatic-like cellular model. NLCs were characterized by dimensions ranging from about 250 to 400 nm. Moreover, the CS coating and FUCO loading determined an increase of size. Moreover, TEM and zeta potential analysis confirmed the presence of CS coating on nanoparticle surface, thus conferring to nanoparticle good bioadhesion properties. NLCs uptake in fibroblasts was observed and NLC-FUCO-CS caused a reduction of cell viability with a less marked effect in fibroblasts rather than in psoriatic cells, highlighting the capability of this system to control skin hyperproliferation and inflammation. The loading of NLC-FUCO-CS in pullulan film should render NLCs application easy, without impair prompt interaction of the drug with the skin. Considering the overall results skin application of CS coated NLCs loaded with FUCO seems a promising approach to control skin hyperproliferation and to preserve skin integrity in psoriatic skin.

Research paper thumbnail of Platelet lysate loaded electrospun scaffolds: Effect of nanofiber types on wound healing

European Journal of Pharmaceutics and Biopharmaceutics, 2019

In healthy individuals, wound healing is a highly efficient process. However, interruptions of no... more In healthy individuals, wound healing is a highly efficient process. However, interruptions of normal healing give rise to chronic wounds, characterized by inflammation with impaired angiogenesis and reepithelialization. The aim of the present work was the design and the development of electrospun nanofibrous scaffolds based on sodium alginate (SA) and pullulan (PUL) and loaded with human platelet lysate (PL) intended for skin reparation, to take the advantage of nanofibrous scaffolds (with improved physical structure) and of SA as biopolymer. Two preparation approaches have been used to load PL in the scaffolds, as component of the PUL/SA matrix to be electrospun or as coating component to cover the previously prepared electrospun PUL based membranes. A preformulation study to assess pullulan entanglement concentration and alginate or citric acid critical concentration to obtain electrospun nanofibers has been performed. The preparation process allowed to obtain insoluble systems starting from aqueous solutions and this were able to act as scaffolds for tissue engineering with suitable mechanical properties and PL release. PL loading in PUL/SA matrix nanofibers did not substantially modify the nanofibers morphology before crosslinking while the crosslinking process in presence of PL determined less sharp nanofibers probably due to an increase in hydrophilicity caused by PL proteins. On the contrary the coated nanofibers showed an increase in diameters due to PL loading. The two different approaches affected the fiber dimension and scaffold elasticity, especially in PL loaded systems. Anyhow, these differences were not crucial for fibroblast adhesion and proliferation which were mainly influenced by PL loading. In particular fibroblasts presented different conformation and orientation mainly due to the presence of PL. This caused a cell random orientation compatible to a fibroblasts-to-myofibroblasts transition that could enhance wound healing.

Research paper thumbnail of Electrospun Alginate Fibers: Mixing of Two Different Poly(ethylene oxide) Grades to Improve Fiber Functional Properties

Nanomaterials, 2018

The aim of the present work was to investigate how the molecular weight (MW) of poly(ethylene oxi... more The aim of the present work was to investigate how the molecular weight (MW) of poly(ethylene oxide) (PEO), a synthetic polymer able to improve alginate (ALG) electrospinnability, could affect ALG-based fiber morphology and mechanical properties. Two PEO grades, having different MWs (high, h-PEO, and low, l-PEO) were blended with ALG: the concentrations of both PEOs in each mixture were defined so that each h-PEO/l-PEO combination would show the same viscosity at high shear rate. Seven ALG/h-PEO/l-PEO mixtures were prepared and characterized in terms of viscoelasticity and conductivity and, for each mixture, a complex parameter rH/rL was calculated to better identify which of the two PEO grades prevails over the other in terms of exceeding the critical entanglement concentration. Thereafter, each mixture was electrospun by varying the process parameters; the fiber morphology and mechanical properties were evaluated. Finally, viscoelastic measurements were performed to verify the for...

Research paper thumbnail of Electrospun Gelatin–Chondroitin Sulfate Scaffolds Loaded with Platelet Lysate Promote Immature Cardiomyocyte Proliferation

Polymers, 2018

The aim of the present work was the development of heart patches based on gelatin (G) and chondro... more The aim of the present work was the development of heart patches based on gelatin (G) and chondroitin sulfate (CS) to be used as implants to improve heart recovery after corrective surgery for critical congenital heart defects (CHD). Patches were prepared by means of electrospinning to obtain nanofibrous scaffolds and they were loaded with platelet lysate (PL) as a source of growth factors to further enhance the repair process. Scaffolds were characterized for morphology and mechanical properties and for the capability to support in vitro adhesion and proliferation of dermal fibroblasts in order to assess the system's general biocompatibility. Adhesion and proliferation of endothelial cells and cardiac cells (cardiomyocytes and cardiac fibroblasts from rat fetuses) onto PL-loaded patches was evaluated. Patches presented good elasticity and high stiffness suitable for in vivo adaptation to heart contraction. CS improved adhesion and proliferation of dermal fibroblasts, as proof of their biocompatibility. Moreover, they enhanced the adhesion and proliferation of endothelial cells, a crucial mediator of cardiac repair. Cell adhesion and proliferation could be related to elastic properties, which could favor cell motility. The presence of platelet lysate and CS was crucial for the adhesion and proliferation of cardiac cells and, in particular, of cardiomyocytes: G/CS scaffold embedded with PL appeared to selectively promote proliferation in cardiomyocytes but not cardiac fibroblasts. In conclusion, G/CS scaffold seems to be a promising system to assist myocardial-repair processes in young patient, preserving cardiomyocyte viability and preventing cardiac fibroblast proliferation, likely reducing subsequent uncontrolled collagen deposition by fibroblasts following repair.

Research paper thumbnail of An In Situ Gelling System for the Local Treatment of Inflammatory Bowel Disease (IBD). The Loading of Maqui (Aristotelia Chilensis) Berry Extract as an Antioxidant and Anti-Inflammatory Agent

Pharmaceutics, 2019

The aim of the present work was the development of an innovative in situ gelling system, to be ap... more The aim of the present work was the development of an innovative in situ gelling system, to be applied on the mucosa of the distal colon via rectal route. The system consisted of three polymers having different functions: gellan (GG), able to jellify in presence of ions; methylcellulose (MC), a thermosensitive polymer with a gelation temperature close to 50 °C; and hydroxypropylcellulose (HPC), a mucoadhesive polymer. The three polymers were able to act synergistically, increasing the permanence of the vehicle on the mucosa and forming a protective gel layer. A DoE approach, “simplex centroid mixture design,” was used to identify the optimal quantitative composition of the vehicle. The response variables considered were: vehicle viscosity at room temperature; increase in vehicle viscosity on increasing temperature (from room to physiological value) and upon dilution with simulated colonic fluid (SCF); and viscoelastic behavior, thixotropic area, and mucoadhesion properties of the ge...

Research paper thumbnail of A Composite Nanosystem as a Potential Tool for the Local Treatment of Glioblastoma: Chitosan-Coated Solid Lipid Nanoparticles Embedded in Electrospun Nanofibers

Polymers

Glioblastoma multiforme (GBM) is one of the most prevalent and aggressive brain tumors for which ... more Glioblastoma multiforme (GBM) is one of the most prevalent and aggressive brain tumors for which there is currently no cure. A novel composite nanosystem (CN), consisting of chitosan-coated Solid Lipid Nanoparticles (c-SLN) embedded in O-carboxymethyl chitosan (O-CMCS)-containing nanofibers (NFs), was proposed as a potential tool for the local delivery of lipophilic anti-proliferative drugs. Coacervation was selected as a solvent-free method for the preparation of stearic acid (SA) and behenic acid (BA)-based SLN (SA-SLN and BA-SLN respectively). BA-SLN, containing 0.75% w/w BA sodium salt and 3% w/w poly(vinyl alcohol) (PVA), were selected for the prosecution of the work since they are characterized by the lowest size functional to their subsequent coating and incorporation in nanofibers. BA-SLN were coated with chitosan (CS) by means of a two-step coating method based on the physical absorption of positively charged CS chains on the SLN negative surface. Nile Red (NR), chosen as t...

Research paper thumbnail of Biomaterials for Soft Tissue Repair and Regeneration: A Focus on Italian Research in the Field

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,...

Research paper thumbnail of Inorganic Nanomaterials in Tissue Engineering

Pharmaceutics

In recent decades, the demand for replacement of damaged or broken tissues has increased; this po... more In recent decades, the demand for replacement of damaged or broken tissues has increased; this poses the attention on problems related to low donor availability. For this reason, researchers focused their attention on the field of tissue engineering, which allows the development of scaffolds able to mimic the tissues’ extracellular matrix. However, tissue replacement and regeneration are complex since scaffolds need to guarantee an adequate hierarchical structured morphology as well as adequate mechanical, chemical, and physical properties to stand the stresses and enhance the new tissue formation. For this purpose, the use of inorganic materials as fillers for the scaffolds has gained great interest in tissue engineering applications, due to their wide range of physicochemical properties as well as their capability to induce biological responses. However, some issues still need to be faced to improve their efficacy. This review focuses on the description of the most effective inorg...

Research paper thumbnail of Smart Device for Biologically Enhanced Functional Regeneration of Osteo–Tendon Interface

Pharmaceutics

The spontaneous healing of a tendon laceration results in the formation of scar tissue, which has... more The spontaneous healing of a tendon laceration results in the formation of scar tissue, which has lower functionality than the original tissue. Moreover, chronic non-healing tendon injuries frequently require surgical treatment. Several types of scaffolds have been developed using the tissue engineering approach, to complement surgical procedures and to enhance the healing process at the injured site. In this work, an electrospun hybrid tubular scaffold was designed to mimic tissue fibrous arrangement and extracellular matrix (ECM) composition, and to be extemporaneously loaded into the inner cavity with human platelet lysate (PL), with the aim of leading to complete post-surgery functional regeneration of the tissue for functional regeneration of the osteo–tendon interface. For this purpose, pullulan (P)/chitosan (CH) based polymer solutions were enriched with hydroxyapatite nanoparticles (HP) and electrospun. The nanofibers were collected vertically along the length of the scaffol...

Research paper thumbnail of Gellan-Based Composite System as a Potential Tool for the Treatment of Nervous Tissue Injuries: Cross-Linked Electrospun Nanofibers Embedded in a RC-33-Loaded Freeze-Dried Matrix

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...

Research paper thumbnail of Development of polyphenol loaded PLGA nanoparticles coated with chitosan oleate

Research paper thumbnail of Nanotechnology-Based Medical Devices for the Treatment of Chronic Skin Lesions: From Research to the Clinic

Pharmaceutics, 2020

Chronic wounds, such as pressure ulcers, diabetic ulcers, venous ulcers and arterial insufficienc... more Chronic wounds, such as pressure ulcers, diabetic ulcers, venous ulcers and arterial insufficiency ulcers, are lesions that fail to proceed through the normal healing process within a period of 12 weeks. The treatment of skin chronic wounds still represents a great challenge. Wound medical devices (MDs) range from conventional and advanced dressings, up to skin grafts, but none of these are generally recognized as a gold standard. Based on recent developments, this paper reviews nanotechnology-based medical devices intended as skin substitutes. In particular, nanofibrous scaffolds are promising platforms for wound healing, especially due to their similarity to the extracellular matrix (ECM) and their capability to promote cell adhesion and proliferation, and to restore skin integrity, when grafted into the wound site. Nanotechnology-based scaffolds are emphasized here. The discussion will be focused on the definition of critical quality attributes (chemical and physical characteriza...

Research paper thumbnail of Stabilization of lemongrass oil nanoemulsions by an ionic amphiphilic derivative of chitosan

Research paper thumbnail of Caratterizzazione del complesso di interazione chitosano-mucina mediante misure viscosimetriche e torbidimetriche

Research paper thumbnail of Water transmission properties and hydration induced modification of hydrocolloid dressings

Research paper thumbnail of In situ Gelling Films loaded with a Carvacrol/Palygorskite hybrid for the treatment of infected skin ulcer

Research paper thumbnail of Relazioni fra forza di disgregazione e penetrazione di acqua nelle compresse: valutazione delle proprietà disgreganti

Chimica Oggi-chemistry Today, 1986

Research paper thumbnail of Effects of Particle Size, Surface Nature and Crystal Type on Dissolution Rate

Particles and Nanoparticles in Pharmaceutical Products, 2018

Solid drug delivery systems are crucial formulations for the oral route. In such systems, particl... more Solid drug delivery systems are crucial formulations for the oral route. In such systems, particle size and polymorphism have a strong impact on drug dissolution and on drug absorption. Starting from the role of particle size in dissolution rate, the Noyes-Whitney equation, the modified form by Nernst-Brunner and the cube root equation are here described. According to these equations diffusion of a solute through a boundary layer around the particles is the rate limiting step for both drug dissolution and absorption and, thus, depends on the specific (external) surface area of the particles, the diffusion coefficient of the dissolved drug, the thickness of the boundary layer and the drug solubility. In relation to this, good wetting of the particle surface by the surrounding liquid and adequate particle dispersion play an essential role. Information from dissolution rates suggests that the thickness of the boundary layer is constant for larger particle sizes, but dependent upon size for smaller particles. Given the larger surface area of smaller particles, the attention has been directed to nanosystems and on their relevance to the bioavailability of poorly soluble drugs. A second advantage of such drug systems is that solubility increases on decreasing particle size, according to the Freundlich–Ostwald equation. The impact of polymorphism, pseudopolymorphism and amorphous form on drug dissolution and bioavailability is also described. Since dissolution and absorption are closely related, the effect of particle size and polymorphism on drug absorption is described. Moreover, regulatory implications of particle size and polymorphism are reviewed.

Research paper thumbnail of Halloysite- and Montmorillonite-Loaded Scaffolds as Enhancers of Chronic Wound Healing

Pharmaceutics, 2020

The increase in life expectancy and the increasing prevalence of diabetic disease and venous insu... more The increase in life expectancy and the increasing prevalence of diabetic disease and venous insufficiency lead to the increase of chronic wounds. The prevalence of ulcers ranges from 1% in the adult population to 3–5% in the over 65 years population, with 3–5.5% of the total healthcare expenditure, as recently estimated. The aim of this work was the design and the development of electrospun scaffolds, entirely based on biopolymers, loaded with montmorillonite (MMT) or halloysite (HNT) and intended for skin reparation and regeneration, as a 3D substrate mimicking the dermal ECM. The scaffolds were manufactured by means of electrospinning and were characterized for their chemico-physical and preclinical properties. The scaffolds proved to possess the capability to enhance fibroblast cells attachment and proliferation with negligible proinflammatory activity. The capability to facilitate the cell adhesion is probably due to their unique 3D structure which are assisting cell homing and...

Research paper thumbnail of Chitosan/Glycosaminoglycan Scaffolds: The Role of Silver Nanoparticles to Control Microbial Infections in Wound Healing

Polymers, 2019

Cutaneous wounds represent a major issue in medical care, with approximately 300 million chronic ... more Cutaneous wounds represent a major issue in medical care, with approximately 300 million chronic and 100 million traumatic wound patients worldwide, and microbial infections slow the healing process. The aim of this work was to develop electrospun scaffolds loaded with silver nanoparticles (AgNPs) to enhance cutaneous healing, preventing wound infections. AgNPs were directly added to polymeric blends based on chitosan (CH) and pullulan (PUL) with hyaluronic acid (HA) or chondroitin sulfate (CS) to be electrospun obtaining nanofibrous scaffolds. Moreover, a scaffold based on CH and PUL and loaded with AgNPs was prepared as a comparison. The scaffolds were characterized by chemico–physical properties, enzymatic degradation, biocompatibility, and antimicrobial properties. All the scaffolds were based on nanofibers (diameters about 500 nm) and the presence of AgNPs was evidenced by TEM and did not modify their morphology. The scaffold degradation was proven by means of lysozyme. Moreove...

Research paper thumbnail of The role of chitosan as coating material for nanostructured lipid carriers for skin delivery of fucoxanthin

International Journal of Pharmaceutics, 2019

Fucoxanthin (FUCO) is a marine carotenoid characterized by antiproliferative properties against h... more Fucoxanthin (FUCO) is a marine carotenoid characterized by antiproliferative properties against hyperproliferative cells. The aim of this work was to design and develop nanostructured lipidic carriers (NLCs) based on bacuri butter and tucumã oil and loaded with FUCO, intended for skin application to prevent skin hyperproliferative diseases and in particular psoriasis. The presence of FUCO should control the hyperproliferation of skin diseased cells and the lipids forming the NLC core, rich in antioxidants and characterized by wound healing properties, should favor the restoring of skin integrity. NLCs were coated with chitosan (CS) to improve their biopharmaceutical properties (bio/mucoadhesion and wound healing) and to combine the advantages of lipidic nanoparticles with the biological properties of CS. Chitosan coated and non-coated NLC were prepared by means of high shear homogenization and characterized for chemico-physical and biopharmaceutical properties (in vitro biocompatibility and cell uptake towards normal dermal human fibroblasts). Moreover, the pharmacological activity of FUCO loaded in NLCs was assessed in psoriatic-like cellular model. NLCs were characterized by dimensions ranging from about 250 to 400 nm. Moreover, the CS coating and FUCO loading determined an increase of size. Moreover, TEM and zeta potential analysis confirmed the presence of CS coating on nanoparticle surface, thus conferring to nanoparticle good bioadhesion properties. NLCs uptake in fibroblasts was observed and NLC-FUCO-CS caused a reduction of cell viability with a less marked effect in fibroblasts rather than in psoriatic cells, highlighting the capability of this system to control skin hyperproliferation and inflammation. The loading of NLC-FUCO-CS in pullulan film should render NLCs application easy, without impair prompt interaction of the drug with the skin. Considering the overall results skin application of CS coated NLCs loaded with FUCO seems a promising approach to control skin hyperproliferation and to preserve skin integrity in psoriatic skin.

Research paper thumbnail of Platelet lysate loaded electrospun scaffolds: Effect of nanofiber types on wound healing

European Journal of Pharmaceutics and Biopharmaceutics, 2019

In healthy individuals, wound healing is a highly efficient process. However, interruptions of no... more In healthy individuals, wound healing is a highly efficient process. However, interruptions of normal healing give rise to chronic wounds, characterized by inflammation with impaired angiogenesis and reepithelialization. The aim of the present work was the design and the development of electrospun nanofibrous scaffolds based on sodium alginate (SA) and pullulan (PUL) and loaded with human platelet lysate (PL) intended for skin reparation, to take the advantage of nanofibrous scaffolds (with improved physical structure) and of SA as biopolymer. Two preparation approaches have been used to load PL in the scaffolds, as component of the PUL/SA matrix to be electrospun or as coating component to cover the previously prepared electrospun PUL based membranes. A preformulation study to assess pullulan entanglement concentration and alginate or citric acid critical concentration to obtain electrospun nanofibers has been performed. The preparation process allowed to obtain insoluble systems starting from aqueous solutions and this were able to act as scaffolds for tissue engineering with suitable mechanical properties and PL release. PL loading in PUL/SA matrix nanofibers did not substantially modify the nanofibers morphology before crosslinking while the crosslinking process in presence of PL determined less sharp nanofibers probably due to an increase in hydrophilicity caused by PL proteins. On the contrary the coated nanofibers showed an increase in diameters due to PL loading. The two different approaches affected the fiber dimension and scaffold elasticity, especially in PL loaded systems. Anyhow, these differences were not crucial for fibroblast adhesion and proliferation which were mainly influenced by PL loading. In particular fibroblasts presented different conformation and orientation mainly due to the presence of PL. This caused a cell random orientation compatible to a fibroblasts-to-myofibroblasts transition that could enhance wound healing.

Research paper thumbnail of Electrospun Alginate Fibers: Mixing of Two Different Poly(ethylene oxide) Grades to Improve Fiber Functional Properties

Nanomaterials, 2018

The aim of the present work was to investigate how the molecular weight (MW) of poly(ethylene oxi... more The aim of the present work was to investigate how the molecular weight (MW) of poly(ethylene oxide) (PEO), a synthetic polymer able to improve alginate (ALG) electrospinnability, could affect ALG-based fiber morphology and mechanical properties. Two PEO grades, having different MWs (high, h-PEO, and low, l-PEO) were blended with ALG: the concentrations of both PEOs in each mixture were defined so that each h-PEO/l-PEO combination would show the same viscosity at high shear rate. Seven ALG/h-PEO/l-PEO mixtures were prepared and characterized in terms of viscoelasticity and conductivity and, for each mixture, a complex parameter rH/rL was calculated to better identify which of the two PEO grades prevails over the other in terms of exceeding the critical entanglement concentration. Thereafter, each mixture was electrospun by varying the process parameters; the fiber morphology and mechanical properties were evaluated. Finally, viscoelastic measurements were performed to verify the for...

Research paper thumbnail of Electrospun Gelatin–Chondroitin Sulfate Scaffolds Loaded with Platelet Lysate Promote Immature Cardiomyocyte Proliferation

Polymers, 2018

The aim of the present work was the development of heart patches based on gelatin (G) and chondro... more The aim of the present work was the development of heart patches based on gelatin (G) and chondroitin sulfate (CS) to be used as implants to improve heart recovery after corrective surgery for critical congenital heart defects (CHD). Patches were prepared by means of electrospinning to obtain nanofibrous scaffolds and they were loaded with platelet lysate (PL) as a source of growth factors to further enhance the repair process. Scaffolds were characterized for morphology and mechanical properties and for the capability to support in vitro adhesion and proliferation of dermal fibroblasts in order to assess the system's general biocompatibility. Adhesion and proliferation of endothelial cells and cardiac cells (cardiomyocytes and cardiac fibroblasts from rat fetuses) onto PL-loaded patches was evaluated. Patches presented good elasticity and high stiffness suitable for in vivo adaptation to heart contraction. CS improved adhesion and proliferation of dermal fibroblasts, as proof of their biocompatibility. Moreover, they enhanced the adhesion and proliferation of endothelial cells, a crucial mediator of cardiac repair. Cell adhesion and proliferation could be related to elastic properties, which could favor cell motility. The presence of platelet lysate and CS was crucial for the adhesion and proliferation of cardiac cells and, in particular, of cardiomyocytes: G/CS scaffold embedded with PL appeared to selectively promote proliferation in cardiomyocytes but not cardiac fibroblasts. In conclusion, G/CS scaffold seems to be a promising system to assist myocardial-repair processes in young patient, preserving cardiomyocyte viability and preventing cardiac fibroblast proliferation, likely reducing subsequent uncontrolled collagen deposition by fibroblasts following repair.