Polyvinylpyrrolidone (PVP) is probably one of the most utilized pharmaceutical polymers with applications ranging from blood plasma substitute to nanoparticle drug delivery since its synthesis in 1938. It is a highly biocompatible, non-toxic and transparent film-forming polymer. Although high solubility of PVP in an aqueous environment is advantageous, it still poses several problems for some applications in which sustained targeting and release are needed, or hydrophobic drug inclusion and delivery systems are to be designed. For this reason, in the field of controlled drug release, it is often used as an additive and not as a protagonist. On the other hand, in case of wound treatment, PVP can be a suitable biopolymer for the design of wound dressings due to its capacity to inhibit the crystallinity of several drugs, opening to their topical application, and its adhesive properties to the skin. Therefore, the main goal of this Ph.D. was to demonstrate that this underestimated synthetic polymer can be a proper based material for the design, the fabrication and the formulation of new smart wound dressings for the delivery of antibiotic and antioxidant compounds. In the first part of this Ph.D. study, PVP and acetic acid (AcOH) were used to inhibit the crystallization of the antibiotic Ciprofloxacin (Cipro) and to prepare transparent PVP foils as well as nanofiber mats. The presence of the antibiotic and the acid inside of the PVP matrix caused a plasticizer effect of these ingredients in the final mechanical properties of the films. Both films and nanofibers were able to release the Cipro, and an antibacterial synergism between acetic acid and the antibiotic were highlighted in vitro antibacterial assay. The PVP/Cipro/AcOH materials showed biocompatibility and a different rate of resorption in an in vivo wound mice model. In the second part of the Ph.D., a multifunctional polyvinylpyrrolidone/hyaluronic acid-based bilayer construct for sequential delivery of cutaneous antiseptic and antibiotic was designed and fabricated by using two scalable methodologies. The bilayer material showed strong adhesion to skin, effective antibacterial activity against three strains, biocompatibility, hemocompatibility, anti-inflammatory properties both in vitro and in vivo, resorption by the skin and accelerate the wound closure in mice model. Then, the PVP/Cipro/AcOH films and nanofibers were further characterized on an infected wound model based on ex-vivo human skin. The materials resulted non-toxic and with suitable profiles of the release of Cipro inside of the skin. Moreover, they highlighted a strong antibacterial activity against biofilms infection of Pseudomonas aeruginosa and, especially, in case of the films they were able to eradicate completely the biofilms from the skin. Finally, PVP was combined with the dietary phenolic compounds, p-coumaric acid (PCA). The introduction of the PCA in transparent films led to an increase of the hydrophobicity of the PVP-based matrix. Indeed, changes in water contact angles, water uptake and the rate of dissolution in water were found. Furthermore, the new biocomposites were investigated as drug delivery system of two model drugs and their antioxidant and anti-inflammatory activity were analyzed in vitro and in vivo, respectively. In conclusions, several PVP-based wound dressings were designed and fabricated, demonstrating their potential efficacy for the treatment of infected wounds, burns, and chronic wounds.

Design and Fabrication of Polyvinylpyrrolidone-based Intelligent Materials Suitable for Controlled Release and Wound Treatment

CONTARDI, MARCO
2019

Abstract

Polyvinylpyrrolidone (PVP) is probably one of the most utilized pharmaceutical polymers with applications ranging from blood plasma substitute to nanoparticle drug delivery since its synthesis in 1938. It is a highly biocompatible, non-toxic and transparent film-forming polymer. Although high solubility of PVP in an aqueous environment is advantageous, it still poses several problems for some applications in which sustained targeting and release are needed, or hydrophobic drug inclusion and delivery systems are to be designed. For this reason, in the field of controlled drug release, it is often used as an additive and not as a protagonist. On the other hand, in case of wound treatment, PVP can be a suitable biopolymer for the design of wound dressings due to its capacity to inhibit the crystallinity of several drugs, opening to their topical application, and its adhesive properties to the skin. Therefore, the main goal of this Ph.D. was to demonstrate that this underestimated synthetic polymer can be a proper based material for the design, the fabrication and the formulation of new smart wound dressings for the delivery of antibiotic and antioxidant compounds. In the first part of this Ph.D. study, PVP and acetic acid (AcOH) were used to inhibit the crystallization of the antibiotic Ciprofloxacin (Cipro) and to prepare transparent PVP foils as well as nanofiber mats. The presence of the antibiotic and the acid inside of the PVP matrix caused a plasticizer effect of these ingredients in the final mechanical properties of the films. Both films and nanofibers were able to release the Cipro, and an antibacterial synergism between acetic acid and the antibiotic were highlighted in vitro antibacterial assay. The PVP/Cipro/AcOH materials showed biocompatibility and a different rate of resorption in an in vivo wound mice model. In the second part of the Ph.D., a multifunctional polyvinylpyrrolidone/hyaluronic acid-based bilayer construct for sequential delivery of cutaneous antiseptic and antibiotic was designed and fabricated by using two scalable methodologies. The bilayer material showed strong adhesion to skin, effective antibacterial activity against three strains, biocompatibility, hemocompatibility, anti-inflammatory properties both in vitro and in vivo, resorption by the skin and accelerate the wound closure in mice model. Then, the PVP/Cipro/AcOH films and nanofibers were further characterized on an infected wound model based on ex-vivo human skin. The materials resulted non-toxic and with suitable profiles of the release of Cipro inside of the skin. Moreover, they highlighted a strong antibacterial activity against biofilms infection of Pseudomonas aeruginosa and, especially, in case of the films they were able to eradicate completely the biofilms from the skin. Finally, PVP was combined with the dietary phenolic compounds, p-coumaric acid (PCA). The introduction of the PCA in transparent films led to an increase of the hydrophobicity of the PVP-based matrix. Indeed, changes in water contact angles, water uptake and the rate of dissolution in water were found. Furthermore, the new biocomposites were investigated as drug delivery system of two model drugs and their antioxidant and anti-inflammatory activity were analyzed in vitro and in vivo, respectively. In conclusions, several PVP-based wound dressings were designed and fabricated, demonstrating their potential efficacy for the treatment of infected wounds, burns, and chronic wounds.
File in questo prodotto:
File Dimensione Formato  
phdunige_4170189.pdf

accesso aperto

Tipologia: Tesi di dottorato
Dimensione 7.13 MB
Formato Adobe PDF
7.13 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11567/939994
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact