Development of electrospun polymer scaffolds for the localized and controlled delivery of siponimod for the management of critical bone defects

Sartawi, Ziad; Waeber, Christian; Schipani, Ernestina; Ryan, Katie B.

doi:10.1016/j.ijpharm.2020.119956

Cited by 8 publications

(5 citation statements)

References 67 publications

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“…These results indicate the thermal instability of siponimod in solution even when incubated at room temperature. This instability might limit the use of suspension and solution-based dosage forms to deliver the drug for ocular applications 52 It is important to note that the storage conditions as indicated on the label of the approved solid-dose, tablet formulation (Mayzent), which contains siponimod as a fumarate cocrystal, take the needed precautions to maintain the drug’s stability for the intended storage duration.…”

Section: Resultsmentioning

confidence: 99%

In Vivo Ocular Pharmacokinetics and Toxicity of Siponimod in Albino Rabbits

Alshaikh,

Salah El Din,

Zaki

et al. 2024

Mol. Pharmaceutics

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Section: Resultsmentioning

confidence: 99%

In Vivo Ocular Pharmacokinetics and Toxicity of Siponimod in Albino Rabbits

Alshaikh,

Salah El Din,

Zaki

et al. 2024

Mol. Pharmaceutics

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“…Unexpectedly, siponimod-loaded PLGA/Col scaffolds demonstrated osteoinductive effects in vitro but failed to promote cranial osteogenesis in vivo. Two pharmacological inhibitors of the enzyme ROCK (Rho-associated coiled-coil kinase), named HA-1077 and Y-27632, adsorbed on Col sponges promoted bone regeneration in cranial CSDs of rats after implantation. The authors suggest that ROCK molecules exert osteoinductive activity in vivo by increasing the osteoblast and osteoclast differentiation and by upregulating the expression of VEGF-A …”

Section: Bioactive Factors Incorporated Into Scaffolds Stimulate Cmf ...mentioning

confidence: 99%

Bioactive Scaffolds as a Promising Alternative for Enhancing Critical-Size Bone Defect Regeneration in the Craniomaxillofacial Region

Bello,

Cruz-Lebrón,

Rodríguez-Rivera

et al. 2023

ACS Appl. Bio Mater.

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Reconstruction of critical-size bone defects (CSDs) in the craniomaxillofacial (CMF) region remains challenging. Scaffold-based bone-engineered constructs have been proposed as an alternative to the classical treatments made with autografts and allografts. Scaffolds, a key component of engineered constructs, have been traditionally viewed as biologically passive temporary replacements of deficient bone lacking intrinsic cues to promote osteogenesis. Nowadays, scaffolds are functionalized, giving rise to bioactive scaffolds promoting bone regeneration more effectively than conventional counterparts. This review focuses on the three approaches most used to bioactivate scaffolds: (1) conferring microarchitectural designs or surface nanotopography; (2) loading bioactive molecules; and (3) seeding stem cells on scaffolds, providing relevant examples of in vivo (preclinical and clinical) studies where these methods are employed to enhance CSDs healing in the CMF region. From these, adding bioactive molecules (specifically bone morphogenetic proteins or BMPs) to scaffolds has been the most explored to bioactivate scaffolds. Nevertheless, the downsides of grafting BMP-loaded scaffolds in patients have limited its successful translation into clinics. Despite these drawbacks, scaffolds containing safer, cheaper, and more effective bioactive molecules, combined with stem cells and topographical cues, remain a promising alternative for clinical use to treat CSDs in the CMF complex replacing autografts and allografts.

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“…Many different 3D models are now in use and may be categorized as matrix or scaffold based and device-assisted models (e.g., rotary flasks, trans-well, bioreactors, microfluidic devices) [175]. 3D models have been designed using a variety of natural and synthetic polymers and different fabrication approaches, heavily influenced by developments in the field of tissue engineering and drug delivery [176,177]. The evolution has given rise to more advanced 3D models incorporating multiple materials, signaling cues and cell types to recapitulate the sophistication inherent in native tissue and mimic the intrinsic biophysical, chemical, and mechanical properties.…”

Section: In Vitro Scaffold/matrix-based Models Of Acute Myeloid Leukemiamentioning

confidence: 99%

Modelling acute myeloid leukemia (AML): What’s new? A transition from the classical to the modern

Dozzo

Galvin

Shin

et al. 2022

Drug Deliv. and Transl. Res.

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Acute myeloid leukemia (AML) is a heterogeneous malignancy affecting myeloid cells in the bone marrow (BM) but can spread giving rise to impaired hematopoiesis. AML incidence increases with age and is associated with poor prognostic outcomes. There has been a disconnect between the success of novel drug compounds observed in preclinical studies of hematological malignancy and less than exceptional therapeutic responses in clinical trials. This review aims to provide a state-of-the-art overview on the different preclinical models of AML available to expand insights into disease pathology and as preclinical screening tools. Deciphering the complex physiological and pathological processes and developing predictive preclinical models are key to understanding disease progression and fundamental in the development and testing of new effective drug treatments. Standard scaffold-free suspension models fail to recapitulate the complex environment where AML occurs. To this end, we review advances in scaffold/matrix-based 3D models and outline the most recent advances in on-chip technology. We also provide an overview of clinically relevant animal models and review the expanding use of patient-derived samples, which offer the prospect to create more “patient specific” screening tools either in the guise of 3D matrix models, microphysiological “organ-on-chip” tools or xenograft models and discuss representative examples. Graphical abstract

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Development of electrospun polymer scaffolds for the localized and controlled delivery of siponimod for the management of critical bone defects

Cited by 8 publications

References 67 publications

In Vivo Ocular Pharmacokinetics and Toxicity of Siponimod in Albino Rabbits

In Vivo Ocular Pharmacokinetics and Toxicity of Siponimod in Albino Rabbits

Bioactive Scaffolds as a Promising Alternative for Enhancing Critical-Size Bone Defect Regeneration in the Craniomaxillofacial Region

Modelling acute myeloid leukemia (AML): What’s new? A transition from the classical to the modern

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