Thermosensitive Hydrogel Incorporating Microspheres for Injectable Implant Delivery of Naltrexone

Long-term drug delivery based on the injectable thermosensitive hydrogel is of great advantage to the administration of naltrexone, but the constant release is hard to reach due to the sol-gel transition and the high water content of the hydrogel. The aim of the present study is to develop an injectable implant delivery system by the incorporation of microspheres into thermosensitive hydrogel for the long-term constant release of naltrexone. Naltrexone was loaded in PLGA microsphere dispersed in the methylcellulose based thermosensitive sol, which formed the hydrogel containing the naltrexone-loaded microspheres at the body temperature. The presence of microsphere in the hydrogel delayed the sol-gel transition slightly but enhanced the mechanical strength of the hydrogel significantly. The microspheres degradation in water diffusion dominated phase was decelerated when they were embed in the hydrogel. The in vitro naltrexone release from the microsphere/hydrogel system showed an over 60 days constant release with no significant burst release, and the drug release rate was in proportion to the microsphere concentration in the hydrogel.

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Preparation and Characterization of Salt-Mediated Injectable Thermosensitive Chitosan/Pectin Hydrogels for Cell Embedding and Culturing

Polymers ◽

10.3390/polym13162674 ◽

2021 ◽

Vol 13 (16) ◽

pp. 2674

Author(s):

Giulia Morello ◽

Alessandro Polini ◽

Francesca Scalera ◽

Riccardo Rizzo ◽

Giuseppe Gigli ◽

...

Keyword(s):

Sol Gel ◽

Polymer Network ◽

Cell Encapsulation ◽

High Water ◽

Biological Tissues ◽

Culture Conditions ◽

Interpenetrating Polymer Network ◽

Sol Gel Transition

In recent years, growing attention has been directed to the development of 3D in vitro tissue models for the study of the physiopathological mechanisms behind organ functioning and diseases. Hydrogels, acting as 3D supporting architectures, allow cells to organize spatially more closely to what they physiologically experience in vivo. In this scenario, natural polymer hybrid hydrogels display marked biocompatibility and versatility, representing valid biomaterials for 3D in vitro studies. Here, thermosensitive injectable hydrogels constituted by chitosan and pectin were designed. We exploited the feature of chitosan to thermally undergo sol–gel transition upon the addition of salts, forming a compound that incorporates pectin into a semi-interpenetrating polymer network (semi-IPN). Three salt solutions were tested, namely, beta-glycerophosphate (βGP), phosphate buffer (PB) and sodium hydrogen carbonate (SHC). The hydrogel formulations (i) were injectable at room temperature, (ii) gelled at 37 °C and (iii) presented a physiological pH, suitable for cell encapsulation. Hydrogels were stable in culture conditions, were able to retain a high water amount and displayed an open and highly interconnected porosity and suitable mechanical properties, with Young’s modulus values in the range of soft biological tissues. The developed chitosan/pectin system can be successfully used as a 3D in vitro platform for studying tissue physiopathology.

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The interplay between chondrocyte spheroids and mesenchymal stem cells boosts cartilage regeneration within a 3D natural-based hydrogel

Scientific Reports ◽

10.1038/s41598-019-51070-7 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Annachiara Scalzone ◽

Ana M. Ferreira ◽

Chiara Tonda-Turo ◽

Gianluca Ciardelli ◽

Kenny Dalgarno ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Sol Gel ◽

Cartilage Regeneration ◽

High Porosity ◽

Young’S Moduli ◽

Chondrogenic Phenotype ◽

Sol Gel Transition ◽

Gel Transition

Abstract Articular cartilage (AC) lacks the ability to self-repair and cell-based approaches, primarily based on using chondrocytes and mesenchymal stem cells (MSCs), are emerging as effective technology to restore cartilage functionality, because cells synergic functionality may support the maintenance of chondrogenic phenotype and promote extracellular matrix regeneration. This work aims to develop a more physiologically representative co-culture system to investigate the influence of MSCs on the activity of chondrocytes. A thermo-sensitive chitosan-based hydrogel, ionically crosslinked with β–glycerophosphate, is optimised to obtain sol/gel transition at physiological conditions within 5 minutes, high porosity with pores diameter <30 µm, and in vitro mechanical integrity with compressive and equilibrium Young’s moduli of 37 kPa and 17 kPa, respectively. Live/dead staining showed that after 1 and 3 days in culture, the encapsulated MSCs into the hydrogels are viable and characterised by round-like morphology. Furthermore chondrocyte spheroids, seeded on top of gels that contained either MSCs or no cells, show that the encapsulated MSCs stimulate chondrocyte activity within a gel co-culture, both in terms of maintaining the coherence of chondrocyte spheroids, leading to a larger quantity of CD44 (by immunofluorescence) and a higher production of collagen and glycosaminoglycans (by histology) compared with the mono-culture.

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Long term effects of bioactive glass particulates on dental pulp stem cells in vitro

Biomedical glasses ◽

10.1515/bglass-2017-0009 ◽

2017 ◽

Vol 3 (1) ◽

Cited By ~ 8

Author(s):

Sanaz Gholami ◽

Sheyda Labbaf ◽

Arezou Baharlou Houreh ◽

Hung-Kai Ting ◽

Julian R. Jones ◽

...

Keyword(s):

Stem Cells ◽

Dental Pulp ◽

Sol Gel ◽

Burst Release ◽

Long Term Effects ◽

Bioactive Glasses ◽

Induce Bone Formation ◽

Sustained Rate

AbstractBioactive glasses (BG) are known for their ability to induce bone formation by the action of their dissolution products. Glasses can deliver active ions at a sustained rate, determined by their composition and surface area. Nanoporous sol-gel derived BGs can biodegrade rapidly, which can lead to a detrimental burst release of ions and a pHrise. The addition of phosphate into the glass can buffer the pH during dissolution. Here, dissolution of BG with composition 60 mol% SiO

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A New Long-Term Composite Drug Delivery System Based on Thermo-Responsive Hydrogel and Nanoclay

Nanomaterials ◽

10.3390/nano11010025 ◽

2020 ◽

Vol 11 (1) ◽

pp. 25

Author(s):

Cezar Tipa ◽

Maria T. Cidade ◽

Tânia Vieira ◽

Jorge Carvalho Silva ◽

Paula I. P. Soares ◽

...

Keyword(s):

Drug Delivery ◽

Sol Gel ◽

Viscous Liquids ◽

Clay Nanoparticles ◽

Viscoelastic Modulus ◽

Sol Gel Transition ◽

Model Drug ◽

In Situ Forming Hydrogels ◽

Gel Transition

Several problems and limitations faced in the treatment of many diseases can be overcome by using controlled drug delivery systems (DDS), where the active compound is transported to the target site, minimizing undesirable side effects. In situ-forming hydrogels that can be injected as viscous liquids and jellify under physiological conditions and biocompatible clay nanoparticles have been used in DDS development. In this work, polymer–clay composites based on Pluronics (F127 and F68) and nanoclays were developed, aiming at a biocompatible and injectable system for long-term controlled delivery of methylene blue (MB) as a model drug. MB release from the systems produced was carried out at 37 °C in a pH 7.4 medium. The Pluronic formulation selected (F127/F68 18/2 wt.%) displayed a sol/gel transition at approx. 30 °C, needing a 2.5 N force to be injected at 25 °C. The addition of 2 wt.% of Na116 clay decreased the sol/gel transition to 28 °C and significantly enhanced its viscoelastic modulus. The most suitable DDS for long-term application was the Na116-MB hybrid from which, after 15 days, only 3% of the encapsulated MB was released. The system developed in this work proved to be injectable, with a long-term drug delivery profile up to 45 days.

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A novel pellets/thermosensitive hydrogel depot with low burst release for long-term continuous drug release: Preparation, characterization, in vitro and in vivo studies

Journal of Drug Delivery Science and Technology ◽

10.1016/j.jddst.2020.102050 ◽

2020 ◽

Vol 60 ◽

pp. 102050

Author(s):

Xueqing Deng ◽

Yangjia Liu ◽

Jianxiu Qin ◽

Tiantian Ye ◽

Shujun Wang

Keyword(s):

Drug Release ◽

In Vivo Studies ◽

Burst Release ◽

Thermosensitive Hydrogel ◽

Release Preparation

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Effect of Mixing Bioactive Nanoceramics with a Thermosensitive Hydrogel as Bone Substitute

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.622-623.1794 ◽

2012 ◽

Vol 622-623 ◽

pp. 1794-1798 ◽

Cited By ~ 1

Author(s):

Po Liang Lai ◽

Ding Wei Hong ◽

Carl Tsai Yu Lin ◽

Lih Huei Chen ◽

Wen Jer Chen ◽

...

Keyword(s):

Animal Studies ◽

Ph Value ◽

Sol Gel ◽

Degradation Process ◽

Thermosensitive Hydrogel ◽

Composite Gels ◽

Bone Graft Substitutes ◽

Sol Gel Transition

The composite of methoxy polyethylene glycol (mPEG) and poly(lactic-co- glycolic acid) (PLGA) thermosensitive hydrogel mixed with different mass raio of hydroxyapatite and β-tricalcium phosphate (β-TCP) were used as bone graft substitutes. The physical properties of a series of composite gels, including the critical micelle concentration (CMC), particle sizes, zeta potential, rheological behavior, morphology of composite gels, and sol–gel transition, were characterized in vitro. These composite gels could form a gel at body temperature and could be controlled easily at room temperature. During the in vitro degradation process, composite gels demonstrated a slight decrease in pH value, a slower degradation rate, less toxicity, and a higher cell survival rate. The biocompatibility of the composite gels was validated by hemolysis test. In vivo animal studies demonstrated both radiographic and gross bone union when the ratio of HAP/ β-TCP was 7:3.

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