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Quality by Design Micro-Engineering Optimisation of NSAID-Loaded Electrospun Fibrous Patches.

ABSTRACT: The purpose of this study was to apply the Quality by Design (QbD) approach to the electrospinning of fibres loaded with the nonsteroidal anti-inflammatory drugs (NSAIDs) indomethacin (INDO) and diclofenac sodium (DICLO). A Quality Target Product Profile (QTPP) was made, and risk assessments (preliminary hazard analysis) were conducted to identify the impact of material attributes and process parameters on the critical quality attributes (CQAs) of the fibres. A full factorial design of experiments (DoE) of 20 runs was built, which was used to carry out experiments. The following factors were assessed: Drugs, voltage, flow rate, and the distance between the processing needle and collector. Release studies exhibited INDO fibres had greater total release of active drug compared to DICLO fibres. Voltage and distance were found to be the most significant factors of the experiment. Multivariate statistical analytical software helped to build six feasible design spaces and two flexible, universal design spaces for both drugs, at distances of 5 cm and 12.5 cm, along with a flexible control strategy. The current findings and their analysis confirm that QbD is a viable and invaluable tool to enhance product and process understanding of electrospinning for the assurance of high-quality fibres.

SUBMITTER: Nazari K

PROVIDER: S-EPMC7022274 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Quality by Design Micro-Engineering Optimisation of NSAID-Loaded Electrospun Fibrous Patches.

Nazari Kazem K Mehta Prina P Arshad Muhammad Sohail MS Ahmed Shahabuddin S Andriotis Eleftherios G EG Singh Neenu N Qutachi Omar O Chang Ming-Wei MW Fatouros Dimitrios G DG Ahmad Zeeshan Z

Pharmaceutics 20191218 1

The purpose of this study was to apply the Quality by Design (QbD) approach to the electrospinning of fibres loaded with the nonsteroidal anti-inflammatory drugs (NSAIDs) indomethacin (INDO) and diclofenac sodium (DICLO). A Quality Target Product Profile (QTPP) was made, and risk assessments (preliminary hazard analysis) were conducted to identify the impact of material attributes and process parameters on the critical quality attributes (CQAs) of the fibres. A full factorial design of experimen ...[more]

PMID: 31861296

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Project description:BackgroundAlthough the use of cardiac patches is still controversial, cardiac patch has the significance in the field of the tissue engineered cardiac regeneration because it overcomes several shortcomings of intra-myocardial injection by providing a template for cells to form a cohesive sheet. So far, fibrous scaffolds fabricated using electrospinning technique have been increasingly explored for preparation of cardiac patches. One of the problems with the use of electrospinning is that nanofibrous structures hardly allow the infiltration of cells for development of 3D tissue construct. In this respect, we have prepared novel bi-modal electrospun scaffolds as a feasible strategy to address the challenges in cardiac tissue engineering .MethodsNano/micro bimodal composite fibrous patch composed of collagen and poly (D, L-lactic-co-glycolic acid) (Col/PLGA) was fabricated using an independent nozzle control multi-electrospinning apparatus, and its feasibility as the stem cell laden cardiac patch was systemically investigated.ResultsNano/micro bimodal distributions of Col/PLGA patches without beaded fibers were obtained in the range of the 4-6% collagen concentration. The poor mechanical properties of collagen and the hydrophobic property of PLGA were improved by co-electrospinning. In vitro experiments using bone marrow-derived mesenchymal stem cells (BMSCs) revealed that Col/PLGA showed improved cyto-compatibility and proliferation capacity compared to PLGA, and their extent increased with increase in collagen content. The results of tracing nanoparticle-labeled as well as GFP transfected BMSCs strongly support that Col/PLGA possesses the long-term stem cells retention capability, thereby allowing stem cells to directly function as myocardial and vascular endothelial cells or to secrete the recovery factors, which in turn leads to improved heart function proved by histological and echocardiographic findings.ConclusionCol/PLGA bimodal cardiac patch could significantly attenuate cardiac remodeling and fully recover the cardiac function, as a consequence of their potent long term stem cell engraftment capability.

Project description:Tissue engineering strategies have emerged in response to the growing prevalence of chronic musculoskeletal conditions, with many of these regenerative methods currently being evaluated in translational animal models. Engineered replacements for fibrous tissues such as the meniscus, annulus fibrosus, tendons, and ligaments are subjected to challenging physiologic loads, and are difficult to track in vivo using standard techniques. The diagnosis and treatment of musculoskeletal conditions depends heavily on radiographic assessment, and a number of currently available implants utilize radiopaque markers to facilitate in vivo imaging. In this study, we developed a nanofibrous scaffold in which individual fibers included radiopaque nanoparticles. Inclusion of radiopaque particles increased the tensile modulus of the scaffold and imparted radiation attenuation within the range of cortical bone. When scaffolds were seeded with bovine mesenchymal stem cells in vitro, there was no change in cell proliferation and no evidence of promiscuous conversion to an osteogenic phenotype. Scaffolds were implanted ex vivo in a model of a meniscal tear in a bovine joint and in vivo in a model of total disc replacement in the rat coccygeal spine (tail), and were visualized via fluoroscopy and microcomputed tomography. In the disc replacement model, histological analysis at 4 weeks showed that the scaffold was biocompatible and supported the deposition of fibrous tissue in vivo. Nanofibrous scaffolds that include radiopaque nanoparticles provide a biocompatible template with sufficient radiopacity for in vivo visualization in both small and large animal models. This radiopacity may facilitate image-guided implantation and non-invasive long-term evaluation of scaffold location and performance.Statement of significanceThe healing capacity of fibrous musculoskeletal tissues is limited, and injury or degeneration of these tissues compromises the standard of living of millions in the US. Tissue engineering repair strategies for the intervertebral disc, meniscus, tendon and ligament have progressed from in vitro to in vivo evaluation using a variety of animal models, and the clinical application of these technologies is imminent. The composition of most scaffold materials however does not allow for visualization by methods available to clinicians (e.g., radiography), and thus it is not possible to assess their performance in situ. In this work, we describe a radiopaque nanofibrous scaffold that can be visualized radiographically in both small and large animal models and serve as a framework for the development of an engineered fibrous tissue.

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Quality by Design Micro-Engineering Optimisation of NSAID-Loaded Electrospun Fibrous Patches.

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Quality by Design Micro-Engineering Optimisation of NSAID-Loaded Electrospun Fibrous Patches.

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