In vitro characterization of physico-chemical properties, cytotoxicity, bioactivity of urea-crosslinked hyaluronic acid and sodium ascorbyl phosphate nasal powder formulation

Fallacara, Arianna; Busato, Laura; Pozzoli, Michele; Ghadiri, Maliheh; Ong, Hui Xin; Young, Paul M.; Manfredini, Stefano; Traini, Daniela

doi:10.1016/j.ijpharm.2019.01.012

Cited by 11 publications

(4 citation statements)

References 66 publications

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“…It has been reported that SAP could act as an antioxidant to protect cultured mouse skin from UVB-induced damage [27]. Further, other researchers have reported that combining a urea-crosslinked hyaluronic acid biopolymer with SAP exerts an enhanced antioxidative and anti-inflammatory activity against several kinds of inflammation-associated diseases [28,29]. Additionally, SAP has been shown to stimulate collagen synthesis in cultures of human dermal fibroblasts, suggesting that SAP is likely to play a crucial role in the wound healing process [30].…”

Section: Introductionmentioning

confidence: 99%

PF-127 hydrogel plus sodium ascorbyl phosphate improves Wharton’s jelly mesenchymal stem cell-mediated skin wound healing in mice

et al. 2020

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Background: Factors such as poor engraftment, retention, and survival of the transplanted stem cells are deemed to limit their therapeutic efficacy for wound regeneration. Hence, it is necessary to explore these issues in order to resolve them. In this study, we aim to investigate the role of Pluronic F-127 (PF-127) hydrogel plus antioxidant sodium ascorbyl phosphate (SAP) in enhancing Wharton's jelly mesenchymal stem cell (WJMSC)-mediated effectiveness on full-thickness skin wound healing in mice. Methods: First, the cytotoxicity of PF-127 and the biological effect of SAP on the survival of WJMSCs were tested in vitro using cell viability and proliferation assays. Next, a cell suspension containing WJMSCs, PF-127, and SAP was topically administered onto an 8-mm diameter excisional full-thickness wound bed. Eight days after transplantation, the mice were sacrificed and the skin tissue was excised for histological and immunohistochemical analysis. Finally, in vivo distribution of transplanted WJMSCs was traced to investigate cell engraftment and the potential therapeutic mechanism. Results: PF-127 was found to be cytotoxic to WJMSCs while SAP significantly improved the survival of PF-127embedded WJMSCs. When this combination was topically transplanted onto the wound bed, wound healing was facilitated and dermis regeneration was achieved on the 8th day after surgery, as evidenced by an increase in dermal thickness, newly developed hair follicles, and collagen fiber deposition accompanied by a reduction in scar width. Further, immunohistochemical analysis demonstrated a higher number of anti-inflammatory M2 macrophages, proliferating cells, and newly formed blood vessels in the WJMSCs/PF-127/SAP group relative to all other groups. In addition, in vivo tracking results revealed a highly enhanced engraftment of WJMSCs accumulated in the dermis in the WJMSCs/PF-127/SAP group. (Continued on next page)Conclusions: SAP significantly improves the survival of WJMSCs in PF-127 encapsulation. Further, PF-127 plus SAP is an effective combination that enhances WJMSC engraftment in the dermis, which then promotes full-thickness wound healing through potential M2 macrophage formation and angiogenesis.

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Section: Introductionmentioning

confidence: 99%

PF-127 hydrogel plus sodium ascorbyl phosphate improves Wharton’s jelly mesenchymal stem cell-mediated skin wound healing in mice

et al. 2020

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“…A general penetration investigation protocol of a pharmaceutical nasal composition includes in vitro, in vitro cell line, ex vivo and in vivo investigations. In vitro studies are carried out using artificial membrane and the development of in vitro models is of great importance in the simplification and quickening of animal studies [20]. Several solutions and methods were carried out to imitate the nasal environment and help to predict the behavior of the tested forms.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Modern In Vitro Permeability Methods with the Aim of Investigation Nasal Dosage Forms

et al. 2021

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Nowadays, the intranasal route has become a reliable alternative route for drug administration to the systemic circulation or central nervous system. However, there are no official in vitro diffusion and dissolution tests especially for the investigation of nasal formulations. Our main goal was to study and compare a well-known and a lesser-known in vitro permeability investigation method, in order to ascertain which was suitable for the determination of drug permeability through the nasal mucosa from different formulations. The vertical diffusion cell (Franz cell) was compared with the horizontal diffusion model (Side-Bi-Side). Raw and nanonized meloxicam containing nasal dosage forms (spray, gel and powder) were tested and compared. It was found that the Side-Bi-Side cell was suitable for the investigation of spray and powder forms. In contrast, the gel was not measurable on the Side-Bi-Side cell; due to its high viscosity, a uniform distribution of the active substance could not be ensured in the donor phase. The Franz cell, designed for the analysis of semi-solid formulations, was desirable for the investigation of nasal gels. It can be concluded that the application of a horizontal cell is recommended for liquid and solid nasal preparations, while the vertical one should be used for semi-solid formulations.

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“…Different natural polymers such as hyaluronic acid (HA), chitosan (CS), gelatin, and carrageenan and also synthetic polymers like poly(vinyl alcohol), oligo(lactic acid), poly(lactic acid), and polymers formed from acrylic acid derivatives have been exploited as excipients for the formulation of pulmonary drug delivery systems [3]. Among different polymers, HA has been frequently reported to have a promising performance, considering its biocompatibility, biodegradability, and non-immunogenicity, which is a requirement for all pulmonary drug delivery systems [12][13][14]. HA is an abundant non-sulfated glycosaminoglycan in the extracellular matrices, composed of the repeating disaccharides units of N-acetyl-D-glucosamine and D-glucuronic acid, connected by alternating β-1,4 and β-1,3 glycosidic bonds.…”

Section: Introductionmentioning

confidence: 99%

Hyaluronic Acid Hydrogels for Controlled Pulmonary Drug Delivery—A Particle Engineering Approach

et al. 2021

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Hydrogels warrant attention as a potential material for use in sustained pulmonary drug delivery due to their swelling and mucoadhesive features. Herein, hyaluronic acid (HA) is considered a promising material due to its therapeutic potential, the effect on lung inflammation, and possible utility as an excipient or drug carrier. In this study, the feasibility of using HA hydrogels (without a model drug) to engineer inhalation powders for controlled pulmonary drug delivery was assessed. A combination of chemical crosslinking and spray-drying was proposed as a novel methodology for the preparation of inhalation powders. Different crosslinkers (urea; UR and glutaraldehyde; GA) were exploited in the hydrogel formulation and the obtained powders were subjected to extensive characterization. Compositional analysis of the powders indicated a crosslinked structure of the hydrogels with sufficient thermal stability to withstand spray drying. The obtained microparticles presented a spherical shape with mean diameter particle sizes from 2.3 ± 1.1 to 3.2 ± 2.9 μm. Microparticles formed from HA crosslinked with GA exhibited a reasonable aerosolization performance (fine particle fraction estimated as 28 ± 2%), whereas lower values were obtained for the UR-based formulation. Likewise, swelling and stability in water were larger for GA than for UR, for which the results were very similar to those obtained for native (not crosslinked) HA. In conclusion, microparticles could successfully be produced from crosslinked HA, and the ones crosslinked by GA exhibited superior performance in terms of aerosolization and swelling.

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In vitro characterization of physico-chemical properties, cytotoxicity, bioactivity of urea-crosslinked hyaluronic acid and sodium ascorbyl phosphate nasal powder formulation

Cited by 11 publications

References 66 publications

PF-127 hydrogel plus sodium ascorbyl phosphate improves Wharton’s jelly mesenchymal stem cell-mediated skin wound healing in mice

PF-127 hydrogel plus sodium ascorbyl phosphate improves Wharton’s jelly mesenchymal stem cell-mediated skin wound healing in mice

Comparison of Modern In Vitro Permeability Methods with the Aim of Investigation Nasal Dosage Forms

Hyaluronic Acid Hydrogels for Controlled Pulmonary Drug Delivery—A Particle Engineering Approach

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