scholarly journals Targeted protein delivery: carbodiimide crosslinking influences protein release from microparticles incorporated within collagen scaffolds

2019 ◽  
Vol 6 (5) ◽  
pp. 279-287 ◽  
Author(s):  
Constantin Edi Tanase ◽  
Omar Qutachi ◽  
Lisa J White ◽  
Kevin M Shakesheff ◽  
Andrew W McCaskie ◽  
...  
Keyword(s):  
Protein Delivery ◽  
Three Dimensional ◽  
Fluorescein Isothiocyanate ◽  
Release Profile ◽  
Protein Release ◽  
Crosslinking Reaction ◽  
Protein Distribution ◽  
Collagen Scaffolds ◽  
Covalent Crosslinking ◽  
Model Protein

Abstract Tissue engineering response may be tailored via controlled, sustained release of active agents from protein-loaded degradable microparticles incorporated directly within three-dimensional (3D) ice-templated collagen scaffolds. However, the effects of covalent crosslinking during scaffold preparation on the availability and release of protein from the incorporated microparticles have not been explored. Here, we load 3D ice-templated collagen scaffolds with controlled additions of poly-(DL-lactide-co-glycolide) microparticles. We probe the effects of subsequent N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride crosslinking on protein release, using microparticles with different internal protein distributions. Fluorescein isothiocyanate labelled bovine serum albumin is used as a model protein drug. The scaffolds display a homogeneous microparticle distribution, and a reduction in pore size and percolation diameter with increased microparticle addition, although these values did not fall below those reported as necessary for cell invasion. The protein distribution within the microparticles, near the surface or more deeply located within the microparticles, was important in determining the release profile and effect of crosslinking, as the surface was affected by the carbodiimide crosslinking reaction applied to the scaffold. Crosslinking of microparticles with a high proportion of protein at the surface caused both a reduction and delay in protein release. Protein located within the bulk of the microparticles, was protected from the crosslinking reaction and no delay in the overall release profile was seen.

Preparation and Evaluation of 6-Maleimidohexanoic Acid Grafted Chitosan Nanoparticles as a Novel Carrier for Intranasal Protein Delivery

2020 ◽  
Vol 859 ◽  
pp. 214-219
Author(s):  
Ekachai Dumkliang ◽  
Tanasait Ngawhirunpat ◽  
Theerasak Rojanarata ◽  
Prasopchai Patrojanasophon ◽  
Boonnada Pamornpathomkul ◽  
...  
Keyword(s):  
Protein Delivery ◽  
Ex Vivo ◽  
Chitosan Nanoparticles ◽  
Fluorescein Isothiocyanate ◽  
Protein Loading ◽  
Before And After ◽  
Model Protein ◽  
Preparation And Evaluation ◽  
Positively Charged

In this study, 6-maleimidohexanoic acid grafted chitosan nanoparticles (MHA-CS NPs) were prepared and evaluated the efficiency of intranasal protein delivery as compared with well-known chitosan nanoparticles (CS NPs). Fluorescein isothiocyanate labelled with bovine serum albumin (FITC-BSA) was used as a model protein. The results indicated that both CS NPs and MHA-CS NPs were positively charged NPs before and after protein loading. The condition for optimal protein loading was 1:6 mass ratio of protein/NPs at 1 h incubation period. The optimal formulations of CS NPs and MHA-CS NPs were evaluated on porcine mucosa as ex vivo. The mucoadhesive and permeation properties of FITC-BSA loaded MHA-CS NPs showed a greater than FITC-BSA loaded CS NPs and FITC-BSA solution, respectively. These ex vivo studies present the potential of MHA-CS NPs as a novel carrier for intranasal protein delivery that will be a candidate for in vivo study.

scholarly journals In VitroandIn VivoInvestigation of the Potential of Amorphous Microporous Silica as a Protein Delivery Vehicle

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Amol Chaudhari ◽  
Lieve Vanmellaert ◽  
Matthias Bauwens ◽  
Peter Vermaelen ◽  
Christophe M. Deroose ◽  
...  
Keyword(s):  
Protein Delivery ◽  
Release Profile ◽  
Burst Release ◽  
Microporous Silica ◽  
Model Protein ◽  
Delivery Platform ◽  
Exploratory Experiment

Delivering growth factors (GFs) at bone/implant interface needs to be optimized to achieve faster osseointegration. Amorphous microporous silica (AMS) has a potential to be used as a carrier and delivery platform for GFs. In this work, adsorption (loading) and release (delivery) mechanism of a model protein, bovine serum albumin (BSA), from AMS was investigatedin vitroas well asin vivo. In general, strong BSA adsorption to AMS was observed. The interaction was stronger at lower pH owing to favorable electrostatic interaction.In vitroevaluation of BSA release revealed a peculiar release profile, involving a burst release followed by a 6 h period without appreciable BSA release and a further slower release later. Experimental data supporting this observation are discussed. Apart from understanding protein/biomaterial (BSA/AMS) interaction, determination ofin vivoprotein release is an essential aspect of the evaluation of a protein delivery system. In this regard micropositron emission tomography (μ-PET) was used in an exploratory experiment to determinein vivoBSA release profile from AMS. Results suggest strongerin vivoretention of BSA when adsorbed on AMS. This study highlights the possible use of AMS as a controlled protein delivery platform which may facilitate osseointegration.

scholarly journals Tunable delayed controlled release profile from layered polymeric microparticles

2017 ◽  
Vol 5 (23) ◽  
pp. 4487-4498 ◽  
Author(s):  
D. Dutta ◽  
C. Fauer ◽  
K. Hickey ◽  
M. Salifu ◽  
S. E. Stabenfeldt
Keyword(s):  
Controlled Release ◽  
Solvent Evaporation ◽  
Release Profile ◽  
Protein Release ◽  
Protein Distribution ◽  
Ethanol Content ◽  
Polymeric Microparticles ◽  
Release Profiles

Solvent evaporation parameters and ethanol content during PLGA/PLLA microparticle (MP) fabrication affect protein distribution and MP structure, thereby altering the protein release profiles.

3D-printed construct from hybrid suspension as spatially and temporally controlled protein delivery system

2021 ◽  
pp. 088532822110232
Author(s):  
Jiangtao Wang ◽  
Baojun Xie ◽  
Zicai Zhu ◽  
Guijun Xie ◽  
Bin Luo
Keyword(s):  
Delivery System ◽  
Protein Delivery ◽  
Matrix Material ◽  
Release Profile ◽  
Protein Release ◽  
Great Promise ◽  
Cytotoxicity Test ◽  
Drug Release Profile ◽  
Theoretical Derivation ◽  
Drying Time

Protein delivery systems have been extensively applied in controlled releasing of protein or polypeptides for therapeutic treatment or tissue regeneration. While 3 D printing technology shows great promise in novel dosage form with tailoring dose size and drug release profile, 3 D printable protein delivery system has to face many difficult challenges. In this study, we developed a hybrid suspension combining Eudragit polyacrylate colloid as matrix material and Pluronic polyether hydrogel as diffusion channel for protein release. This hybrid suspension can be 3 D-printed into construct with complex shape and inner structures thanks to its pseudoplastic and thixotropic rheological properties. The protein can be incorporated in hybrid suspension either in its original or nanoparticle capsulated form. The experiment shows that the protein release from construct is a function of drying time, molecular weight (MW) of chitosan, as well as their own structural/diffusional properties. Also, the theoretical derivation suggests polyacrylate matrix tortuosity, chitosan erosion rate as well as hydrogel diffusion coefficient all contributed to the extended duration of release profile. In addition, cytotoxicity test through cell culture confirmed that the construct fabricated from hybrid suspension exhibit relative good bio-compatibility. Finally, heterogeneous constructs with zoned design were fabricated as protein delivery system, which demonstrated the capability of hybrid suspension technique for spatial and temporal release of macromolecular drugs to realize pharmaceutical effectiveness or guild cell organization.

Extrusion-Based 3D Printing for Pharmaceuticals: Contemporary Research and Applications

2019 ◽  
Vol 24 (42) ◽  
pp. 4991-5008 ◽  
Author(s):  
Mohammed S. Algahtani ◽  
Abdul Aleem Mohammed ◽  
Javed Ahmad
Keyword(s):  
Cosmetic Surgery ◽  
Fused Deposition Modeling ◽  
Personalised Medicine ◽  
Organ Transplant ◽  
Three Dimensional ◽  
Dosage Forms ◽  
Release Profile ◽  
Small Scale ◽  
Drug Release Profile ◽  
Fused Deposition

Three-dimensional printing (3DP) has a significant impact on organ transplant, cosmetic surgery, surgical planning, prosthetics and other medical fields. Recently, 3 DP attracted the attention as a promising method for the production of small-scale drug production. The knowledge expansion about the population differences in metabolism and genetics grows the need for personalised medicine substantially. In personalised medicine, the patient receives a tailored dose and the release profile is based on his pharmacokinetics data. 3 DP is expected to be one of the leading solutions for the personalisation of the drug dispensing. This technology can fabricate a drug-device with complicated geometries and fillings to obtain the needed drug release profile. The extrusionbased 3 DP is the most explored method for investigating the feasibility of the technology to produce a novel dosage form with properties that are difficult to achieve using the conventional industrial methods. Extrusionbased 3 DP is divided into two techniques, the semi-solid extrusion (SSE) and the fused deposition modeling (FDM). This review aims to explain the extrusion principles behind the two techniques and discuss their capabilities to fabricate novel dosage forms. The advantages and limitations observed through the application of SSE and FDM for fabrication of drug dosage forms were discussed in this review. Further exploration and development are required to implement this technology in the healthcare frontline for more effective and personalised treatment.

scholarly journals Effect of Uniaxial Tensile Cyclic Loading Regimes on Matrix Organization and Tenogenic Differentiation of Adipose-Derived Stem Cells Encapsulated within 3D Collagen Scaffolds

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Gayathri Subramanian ◽  
Alexander Stasuk ◽  
Mostafa Elsaadany ◽  
Eda Yildirim-Ayan
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Expression Profiles ◽  
Three Dimensional ◽  
Uniaxial Tensile ◽  
Adipose Derived Stem Cells ◽  
Collagen Scaffolds ◽  
Differentiation Potential ◽  
Tenogenic Differentiation ◽  
Matrix Organization

Adipose-derived mesenchymal stem cells have become a popular cell choice for tendon repair strategies due to their relative abundance, ease of isolation, and ability to differentiate into tenocytes. In this study, we investigated the solo effect of different uniaxial tensile strains and loading frequencies on the matrix directionality and tenogenic differentiation of adipose-derived stem cells encapsulated within three-dimensional collagen scaffolds. Samples loaded at 0%, 2%, 4%, and 6% strains and 0.1 Hz and 1 Hz frequencies for 2 hours/day over a 7-day period using a custom-built uniaxial tensile strain bioreactor were characterized in terms of matrix organization, cell viability, and musculoskeletal gene expression profiles. The results displayed that the collagen fibers of the loaded samples exhibited increased matrix directionality with an increase in strain values. Gene expression analyses demonstrated that ASC-encapsulated collagen scaffolds loaded at 2% strain and 0.1 Hz frequency showed significant increases in extracellular matrix genes and tenogenic differentiation markers. Importantly, no cross-differentiation potential to osteogenic, chondrogenic, and myogenic lineages was observed at 2% strain and 0.1 Hz frequency loading condition. Thus, 2% strain and 0.1 Hz frequency were identified as the appropriate mechanical loading regime to induce tenogenic differentiation of adipose-derived stem cells cultured in a three-dimensional environment.

Release Profile of a Model Protein Drug Depending on the Stability of Microspheres Based on Polyelectrolyte Complex

2007 ◽  
Vol 342-343 ◽  
pp. 505-508
Author(s):  
Sung Won Kim ◽  
Yun Sik Nam ◽  
Yeon Jin Min ◽  
Jong Ho Kim ◽  
Kwang Meyong Kim ◽  
...  
Keyword(s):  
Polyelectrolyte Complex ◽  
Coating Layer ◽  
Great Influence ◽  
Release Profile ◽  
Core Material ◽  
Glycol Chitosan ◽  
The Core ◽  
Key Factor ◽  
Model Protein ◽  
The Stability

Stability and disintegration of natural polyelectrolyte complex microspheres for protein drugs delivery have been extensively investigated because of their great influence on the drug release patterns. In this study, we tested stability of microspheres with alginate (Alg) core layered by either chitosan (Chi) or glycol chitosan (GChi) by examining release profiles of fluorophorelabeled bovine serum albumin (BSA) and lysozyme (Lys) from the microspheres. While GChi shell was disintegrated quickly, Chi-shell microspheres showed good stability in PBS. Disintegration of the coated layer induced the core material instable. The results indicated that while the charges of the shell material provided additional diffusion barrier against the protein release, the key factor to hold the proteins inside the microspheres was the integrity of the outer coating layer.

scholarly journals Inhibitors of A Disintegrin And Metalloproteinases-10 reduce Hodgkin lymphoma cell growth in 3D microenvironments and enhance brentuximab-vedotin effect

Haematologica ◽  
2021 ◽  
Author(s):  
Roberta Pece ◽  
Sara Tavella ◽  
Delfina Costa ◽  
Serena Varesano ◽  
Caterina Camodeca ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Drug Testing ◽  
Cell Damage ◽  
Three Dimensional ◽  
3D Culture ◽  
Glucose Consumption ◽  
3D Models ◽  
Brentuximab Vedotin ◽  
Collagen Scaffolds ◽  
Antibody Drug Conjugate

Shedding of A Disintegrin And Metalloproteinases (ADAM10) substrates, like TNFα or CD30, can affect both anti-tumor immune response and antibody-drug-conjugate (ADC)-based immunotherapy. We have published two new ADAM10 inhibitors, LT4 and MN8 able to prevent such shedding in Hodgkin lymphoma (HL). Since tumor tissue architecture deeply influence the outcome of anti-cancer treatments, we set up new three-dimensional (3D) culture systemsto verify whether ADAM10 inhibitors can contribute to, or enhance, the anti-lymphoma effects of the ADC brentuximab-vedotin (BtxVed).To recapitulate some aspects of lymphoma structure and architecture, we assembled two 3D culture models: mixed spheroids made of HL lymph node (LN) mesenchymal stromal cells (MSC) and Reed Sternberg/Hodgkin lymphoma cells (HL cells) or collagen scaffolds repopulated with LN-MSC and HL cells. In these 3D systems we found that: 1) the ADAM10 inhibitors LT4 and MN8 reduce ATP content or glucose consumption, related to cell proliferation, increasing lactate dehydrogenase (LDH) release as a cell damage hallmark; 2) these events are paralleled by mixed spheroids size reduction and inhibition of CD30 and TNFα shedding; 3) the effects observed can be reproduced in repopulated HL LN-derived matrix or collagen scaffolds; 4) ADAM10 inhibitors enhance the antilymphoma effect of the anti-CD30 ADC BtxVed both in conventional cultures and in repopulated scaffolds. Thus, we provide evidence for direct and combined anti-lymphoma effect of ADAM10 inhibitors with BtxVed, leading to improvement of ADC effects; this is documented in 3D models recapitulating features of LN microenvironment, that can be proposed as reliable tool for antilymphoma drug testing.

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