Co-Spray-Dried Urea Cross-Linked Hyaluronic Acid and Sodium Ascorbyl Phosphate as Novel Inhalable Dry Powder Formulation

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

doi:10.1016/j.xphs.2019.04.015

Cited by 13 publications

(5 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Microparticles formed from HA crosslinked with GA (HAGA) thus presented a higher mFPF compared to those for the HA and HAUR microparticles. The obtained mFPF for HAGA is consistent with data reported for spray-dried inhalation powders comprising different polymers, APIs and other additives [12,23,35,36,45,55,60]. However, the mFPF for the HA and HAUR microparticles is lower than typical FPFs reported for the similar formulations.…”

Section: Aerodynamic Propertiessupporting

confidence: 88%

“…The feed rate of 0.1 mL/min, aspiration gas flow of 30 L/h, inlet temperature 120 • C and atomizing air-flow of 357 L/h were selected as optimized process conditions and the related formulations HA3 (also referred to as merely HA), HAGA, and HAUR (Table 1) were prepared for further characterization. It is worth mentioning that the obtained particle sizes and size distributions are in line with prior results reported for spray-dried HA powder formulations for pulmonary drug delivery [12,23,35,36]. Spray drying of hydrogels is challenging; however, the narrow size distribution (span = 1.2 and 1.3) and mean diameters around 2.2 µm for the crosslinked HA confirm the possibility of using spray drying for preparation of inhalable dry powders based on hydrogels.…”

Section: Process Conditions and Particle Size Analysissupporting

confidence: 87%

“…The microparticles based on native and crosslinked HA presented a spherical shape and very smooth surfaces with no apparent macroporosity. This morphology is distinct from the one observed in prior studies, in which less smooth particles typically were produced, and may be caused by the absence of additional additives (API or other excipients) or a different structure and rheology of the feed suspension [12,23,35,36,45]. During spray drying, solidification is initiated at the surface of the droplets.…”

Section: Scanning Electron Microscopy (Sem)contrasting

confidence: 61%

See 2 more Smart Citations

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

et al. 2021

View full text Add to dashboard Cite

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.

show abstract

Section: Aerodynamic Propertiessupporting

confidence: 88%

Section: Process Conditions and Particle Size Analysissupporting

confidence: 87%

Section: Scanning Electron Microscopy (Sem)contrasting

confidence: 61%

See 1 more Smart Citation

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

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Use of hyaluronic acid as a therapeutic active pharmaceutical ingredient or as a functional delivery vehicle presents numerous advantages, among which the extensive available in vitro and clinical data, an excellent biocompatibility, and a large industrial hindsight around raw material sourcing and product manufacturing [68][69][70]. Along with its natural presence in human tissues, high biocompatibility and safety characterize HA-based formulas, which have been notably used for treating tendinopathies or burn wounds and were recently considered for various inhalation applications [7,71,72]. On the other hand, inclusion of progenitor tenocyte derivative APIs in therapeutic products or medical devices is technically enabled from a safety and quality point of view by the extensive traceability, testing, and qualification steps performed during the cell sourcing phase and during subsequent GMP cell banking [44].…”

Section: Progenitor Tenocyte Derivative Apis and Ha Combination Products Present Several Technical Advantagesmentioning

confidence: 99%

Combination of Hyaluronan and Lyophilized Progenitor Cell Derivatives: Stabilization of Functional Hydrogel Products for Therapeutic Management of Tendinous Tissue Disorders

et al. 2021

View full text Add to dashboard Cite

Cultured progenitor cells and derivatives have been used in various homologous applications of cutaneous and musculoskeletal regenerative medicine. Active pharmaceutical ingredients (API) in the form of progenitor cell derivatives such as lysates and lyophilizates were shown to retain function in controlled cellular models of wound repair. On the other hand, hyaluronan-based hydrogels are widely used as functional vehicles in therapeutic products for tendon tissue disorders. The aim of this study was the experimental characterization of formulations containing progenitor tenocyte-derived APIs and hyaluronan, for the assessment of ingredient compatibility and stability in view of eventual therapeutic applications in tendinopathies. Lyophilized APIs were determined to contain relatively low quantities of proteins and growth factors, while being physicochemically stable and possessing significant intrinsic antioxidant properties. Physical and rheological quantifications of the combination formulas were performed after hydrogen peroxide challenge, outlining significantly improved evolutive viscoelasticity values in accelerated degradation settings. Thus, potent effects of physicochemical protection or stability enhancement of hyaluronan by the incorporated APIs were observed. Finally, combination formulas were found to be easily injectable into ex vivo tendon tissues, confirming their compatibility with further translational clinical approaches. Overall, this study provides the technical bases for the development of progenitor tenocyte derivative-based injectable therapeutic products or devices, to potentially be applied in tendinous tissue disorders.

show abstract

“…As a sodium salt of ascorbic acid 2-phosphate, sodium ascorbyl phosphate (SAP) can maintain high stability even when exposed to reactive oxygen species and aqueous solution for a long time 21 . It was found that SAP exerted multiple pharmacological activities, such as antioxidant, anti-inflammatory, immunostimulant, and anti-bacterial actions 22 . The antioxidant property of SAP has been investigated profoundly of late 23 .…”

Section: Introductionmentioning

confidence: 99%

Thermosensitive hydrogel coupled with sodium ascorbyl phosphate promotes human umbilical cord-derived mesenchymal stem cell-mediated skin wound healing in mice

Liu¹,

Sheng²,

Mao³

et al. 2023

Sci Rep

View full text Add to dashboard Cite

Poor survival and restricted function of transplanted stem cells are regarded as limiting their efficacy in wound recovery greatly. Consequently, it is necessary to identify innovative therapeutic strategies to solve these issues. Firstly, the biological effect of PF-127 hydrogel alone and in combination with SAP on the survival, and migration of cultured HUCMSCs was assessed by cell viability, apoptosis, and scratch wound assays. S. aureus and E. coli were used to evaluate the antibacterial activity of PF-127 plus SAP combination. Further, the ability of HUCMSCs-conditioned medium (HUCMSCs-CM) to promote the angiogenesis and migration of human umbilical vein endothelial cells (HUVECs) in vitro was evaluated using tube formation and transwell migration assays. Finally, the HUCMSCs embedded in PF-127 plus SAP scaffold were administered onto mice’s excisional cutaneous wound bed. Histological and immunohistochemical analyses were employed to investigate the wound healing capacity as well as cellular responses of PF-127/HUCMSCs/SAP hydrogel. PF-127 showed cytotoxicity on HUCMSCs, whereas the addition of SAP significantly promoted cell viability and alleviated apoptosis of HUCMSCs encapsulated in PF-127 hydrogel in vitro. SAP supplementation substantially abrogated the inhibiting effect of PF-127 on the migration of HUCMSCs in vitro. The combination of PF-127 and SAP exerted an obvious bacteriostatic function on S. aureus and E. coli. Moreover, the co-treatment with SAP could remarkably enhance the stimulative effect of HUCMSCs-CM on the angiogenesis and migration of HUVECs in vitro. PF-127 combined SAP-embedded HUCMSCs transplantation resulted in a potently accelerated wound healing process, promoted the number of proliferating cells and newly formed blood vessels, as well as enhanced expression of vascular endothelial growth factor. PF-127 coupled with SAP contributes to HUCMSCs-mediated traumatic wound closure in mice by promoting cell survival, antibacterial action, and angiogenesis. Our results offered a theoretical foundation for the clinical treatment of traumatic skin defects.

show abstract

Co-Spray-Dried Urea Cross-Linked Hyaluronic Acid and Sodium Ascorbyl Phosphate as Novel Inhalable Dry Powder Formulation

Cited by 13 publications

References 43 publications

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

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

Combination of Hyaluronan and Lyophilized Progenitor Cell Derivatives: Stabilization of Functional Hydrogel Products for Therapeutic Management of Tendinous Tissue Disorders

Thermosensitive hydrogel coupled with sodium ascorbyl phosphate promotes human umbilical cord-derived mesenchymal stem cell-mediated skin wound healing in mice

Contact Info

Product

Resources

About