Delivery of Active FGF-2 From Mechanically-Stable Biological Nanofibers Accelerates Cell Ingress Into Multifiber Composites

Author(s):  
Jonathan A. Kluge ◽  
Rudra A. Pampati ◽  
Mara L. Schenker ◽  
Daniel J. Zhou ◽  
John E. Esterhai ◽  
...  

Fibrocartilaginous tissues such as the meniscus and annulus fibrosus serve critical load-bearing roles, relying on arrays of highly organized collagen fibers to resist tensile loads [1]. As these specialized structures are often injured, there exists great demand for engineered tissues for repair or replacement. Cell-laden aligned nanofibrous scaffolds formed from poly(ε-caprolactone) (PCL) have shown promise in achieving tissuelike mechanical and biochemical properties and can direct cellular and matrix organization in vitro [2]. A current limitation of nanofibrous scaffolds, however, is a slow rate of cellular infiltration, particularly in thick scaffolds. To address this, dynamic composite nanofibrous scaffolds have been fabricated via multi-fiber spinning [3], which can offer tunable modes of degradation depending on the polymer sources. For example, water-soluble polyethylene oxide (PEO) fibers can be co-spun with PCL to improve porosity and hasten cell ingress [4]. Incorporation of additional tunable and bioactive polymer sources may add greater versatility to these composite systems. For example, aqueous-based silk fibroin can be used as a slow-degrading, mechanically strong composite fiber component [5] into which active biologic factors (drugs, growth factors) can be incorporated [6]. Variably-degradable silk fibers can be formed by modulating post-spinning treatments, and protein release kinetics can likewise be manipulated by the physical crosslinking method [7]. We hypothesized that incorporation of robust and tunable silk protein-based fibers into a composite of slow-degrading synthetic fibers would provide mechanical function while delivering active biologic factors to expedite cell proliferation and encourage more rapid construct colonization. To test this hypothesis, we characterized the release kinetics of recombinant FGF-2 from silk fibers and its bioactivity in vitro and in a rat subcutaneous implant model.

2021 ◽  
Vol 1 (2) ◽  
pp. 023-037
Author(s):  
Shailaja D ◽  
Latha K ◽  
Manasa D ◽  
Shirisha A ◽  
Padmavathi R ◽  
...  

Proniosomal technology is a novel solution for poorly soluble drugs. Proniosomes are water-soluble carrier particles which are coated with non-ionic surfactants. Proniosomal gels were prepared by coacervation phase separation method using non-ionic surfactants, lipid carriers and cholesterol as a membrane stabilizer. FTIR compatibility studies revealed that the drug and excipients were compatible. All formulations were evaluated for pH, drug content, extrudability, spreadability, viscosity, in-vitro, ex-vivo, skin irritation and stability studies. Among formulations prepared, F80H1 has shown higher % EE (83.02) and least diffusion through dialysis membrane i.e., 17.68%. With ex-vivo studies, F80H1 formulation has shown highest skin deposition and lower flux of sertaconazole nitrate through the rat skin. F80H1 was selected as final optimized formulation. F80H1 exhibited good stability and SEM studies revealed that the vesicles were spherical in shape. The optimized formulation was found to follow zero order release kinetics and korsmeyer-peppas release mechanism. F80H1 found to be non-irritant and stable from skin irritation and stability studies.


Author(s):  
Preethi G. B. ◽  
Prashanth Kunal

<p><strong>Objective: </strong>The current work was attempted to formulate and evaluate a controlled-release matrix-type ocular inserts containing a combination of brimonidine tartrate and timolol maleate, with a view to sustain the drug release in the cul-de-sac of the eye.<strong></strong></p><p><strong>Methods: </strong>Initially, the infrared studies were done to determine the drug–polymer interactions. Sodium alginate-loaded ocuserts were prepared by solvent casting technique. Varying the concentrations of polymer—sodium alginate, plasticizer—glycerine, and cross-linking agent—calcium chloride by keeping the drug concentration constant, made a total of nine formulations. These formulations were evaluated for its appearance, drug content, weight uniformity, thickness uniformity, percentage moisture loss, percentage moisture absorption, and <em>in vitro </em>release profile of the ocuserts. Finally, accelerated stability studies and the release kinetics were performed on the optimised formulation.<strong></strong></p><p><strong>Results: </strong>It was perceived that polymer, plasticizer, and calcium chloride had a significant influence on the drug release. The data obtained from the formulations showed that formulation—F9 was the optimised formulation, which exhibited better drug release. The release data of the optimised formulation tested on the kinetic models revealed that it exhibited first-order release kinetics. <strong></strong></p><p><strong>Conclusion: </strong>It can be concluded that a natural bioadhesive hydrophilic polymer such as sodium alginate can be used as a film former to load water soluble and hydrophilic drugs like brimonidine tartrate and timolol maleate. Among all formulations, F9 with 400 mg sodium alginate, 2% calcium chloride and 60 mg glycerin were found to be the most suitable insert in terms of appearance, ease of handling, thickness, <em>in vitro</em> drug release and stability.</p>


2020 ◽  
Author(s):  
Afshin Fathi ◽  
Mehdi Khanmohammadi ◽  
Arash Goodarzi ◽  
Lale Foroutani ◽  
Zahra Taherian Mobarakeh ◽  
...  

Abstract Hybrid fibrous mat containing cell interactive molecules offers the ability to deliver the cells and drugs in wound bed, which will help to achieve a high therapeutic treatment. In this study, a co-electrospun hybrid of polyvinyl alcohol (PVA), chitosan (Ch) and silk fibrous mat was developed and their wound healing potential by localizing bone marrow mesenchymal stem cells (MSCs)-derived keratinocytes on it was evaluated in vitro and in vivo. It was expected that fabricated hybrid construct could promote wound healing due to its structure, physical, biological specifications. The fabricated fibrous mats were characterized for their structural, mechanical and biochemical properties. The shape uniformity and pore size of fibers showed smooth and homogenous structures of them. Fourier transform infrared spectroscopy (FTIR) verified all typical absorption characteristics of Ch-PVA + Silk polymers as well as Ch-PVA or pure PVA substrates. The contact angle and wettability measurement of fibers showed that mats found moderate hydrophilicity by addition of Ch and silk substrates compared with PVA alone. The mechanical features of Ch-PVA + Silk fibrous mat increase significantly through co-electrospun process as well as hybridization of these synthetic and natural polymers. Higher degrees of cellular attachment and proliferation obtained on Ch-PVA + Silk fibers compared with PVA and Ch-PVA fibers. In terms of the capability of Ch-PVA + Silk fibers and MSC-derived keratinocytes, histological analysis and skin regeneration results showed this novel fibrous construct could be suggested as a skin substitute in the repair of injured skin and regenerative medicine applications.


Author(s):  
S. DUBEY ◽  
S. P. VYAS

Objective: The objective of the present study was to formulate and characterize paclitaxel (Ptx) loaded sterically stabilized emulsomes to provide non-toxic and biocompatible carriers with high Ptx loading efficiency. Methods: Plain (P-Es) and sterically stabilized emulsomes (SS-Es) were prepared by a modified solvent evaporation method using tristearin as solid lipid and optimized for lipid to (DSPC+CHOL+DSPE-PEG)/ tristearin ratio, lipid/lipid-PEG (DSPC+CHOL/DSPE-PEG) molar ratio, solid lipid concentration, phospholipid concentration, organic to aqueous phase volume and homogenization time based on their effect particle size and entrapment efficiency. Optimized emulsomes were characterized for morphological features, in vitro drug release kinetics and protection from plasma protein. Results: The emulsomes so formed were uniform in size with a mean particle diameter of 275±5.52 and 195±6.4 nm for P-Es and SS-Es respectively. All the formulations showed pH dependent drug release with a slow and sustained release profile. Slower drug release was observed from sterically stabilized emulsomes than the plain emulsomes. The drug release profile followed the Higuchi model with the Fickian diffusion pattern. The Pegylation of emulsomes significantly reduced the in vitro protein absorption. Conclusion: The sterically stabilized emulsome can serve as a novel non-toxic platform with longer circulatory time for the delivery of Paclitaxel and other poorly water-soluble drugs as well.


2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Afshin Fathi ◽  
Mehdi Khanmohammadi ◽  
Arash Goodarzi ◽  
Lale Foroutani ◽  
Zahra Taherian Mobarakeh ◽  
...  

AbstractHybrid fibrous mat containing cell interactive molecules offers the ability to deliver the cells and drugs in wound bed, which will help to achieve a high therapeutic treatment. In this study, a co-electrospun hybrid of polyvinyl alcohol (PVA), chitosan (Ch) and silk fibrous mat was developed and their wound healing potential by localizing bone marrow mesenchymal stem cells (MSCs)-derived keratinocytes on it was evaluated in vitro and in vivo. It was expected that fabricated hybrid construct could promote wound healing due to its structure, physical, biological specifications. The fabricated fibrous mats were characterized for their structural, mechanical and biochemical properties. The shape uniformity and pore size of fibers showed smooth and homogenous structures of them. Fourier transform infrared spectroscopy (FTIR) verified all typical absorption characteristics of Ch-PVA + Silk polymers as well as Ch-PVA or pure PVA substrates. The contact angle and wettability measurement of fibers showed that mats found moderate hydrophilicity by addition of Ch and silk substrates compared with PVA alone. The mechanical features of Ch-PVA + Silk fibrous mat increase significantly through co-electrospun process as well as hybridization of these synthetic and natural polymers. Higher degrees of cellular attachment and proliferation obtained on Ch-PVA + Silk fibers compared with PVA and Ch-PVA fibers. In terms of the capability of Ch-PVA + Silk fibers and MSC-derived keratinocytes, histological analysis and skin regeneration results showed this novel fibrous construct could be suggested as a skin substitute in the repair of injured skin and regenerative medicine applications.


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Giuseppe Caputo

Supercritical adsorption coupled with the high adsorption capacity of silica aerogel allows the preparation of a new kind of delivery systems of poor water soluble drugs. In order to overcome drawbacks of conventional techniques where the use of liquid solvents can cause the fracture of aerogel porous structure, in this work a new adsorption process of drugs from a supercritical mixture is proposed. Adsorption takes place from a fluid solution of the drug in supercritical CO2and ethanol as cosolvent. A fixed bed adsorption plant has been developed to allow fast mixing of fluid phase and effective contact in the adsorption column. The use of ethanol as cosolvent allows to overcome the limitation of supercritical adsorption due to low solubility of many drugs in supercritical CO2. Adsorption isotherms were measured for one-model substance, nimesulide, at 40°C, and breakthrough curve was experimentally obtained. The drug loading of the drug into silica aerogel was up to 9 wt%. The drug composite was characterized using scanning electron microscopy, and release kinetics of the adsorbed drug were also evaluated by in vitro dissolution tests. The dissolution of nimesulide from loaded aerogel is much faster than dissolution of crystalline nimesulide. Around 80% of nimesulide dissolves from the aerogel within 6 minutes, whereas dissolving 80% of the crystalline drug takes about 90 min.


1970 ◽  
Vol 6 (2) ◽  
pp. 87-92
Author(s):  
Golam Kibria ◽  
Reza-ul Jalil

In the present study an attempt has been made to investigate the effect of ethylcellulose as a rate retarding material to sustain the release of diltiazem hydrochloride from pellets prepared by air suspension technique. Aqueous ethylcellulose dispersion (Surelease) with different weight ratios was chosen to sustain the release of the drug. Drug was loaded on dummy seeds by following matrix system as well as barrier coating system. The comparative study of this two manufacturing processes was also the goal of this study. In vitro dissolution studies were carried out using USP dissolution apparatus Type-2. The release of drug was faster from matrix system than that of barrier coating system. About 100% drug was released within 3 hours with 5% polymer load from both systems. While the polymer content was 10%, about 4h & 7h required for 50% & 80% drug release respectively from barrier coating system. The effect of ethylcellulose on the release of diltiazem hydrochloride was found to be predominant in barrier coating system than that of the matrix system. In the matrix system the drug comes to dissolution media easily and water soluble additives form channel very fast. The kinetic study of the drug was performed and it was revealed that the release of drug from pellets appeared to follow zero order kinetics. Key words: Diltiazem; Pellets; Pseudolatex; Aqueous coating; Manufacturing process; Release kinetics. Dhaka Univ. J. Pharm. Sci. 6(2): 87-92, 2007 (December)


2020 ◽  
Author(s):  
Afshin Fathi ◽  
Mehdi Khanmohammadi ◽  
Arash Goodarzi ◽  
Lale Foroutani ◽  
Zahra Taherian Mobarakeh ◽  
...  

Abstract Hybrid fibrous mat containing cell interactive molecules offers the ability to deliver the cells and drugs in wound bed, which will help to achieve a high therapeutic treatment. In this study, a co-electrospun hybrid of polyvinyl alcohol (PVA), chitosan (Ch) and silk fibrous mat was developed and their wound healing potential by localizing bone marrow mesenchymal stem cells (MSCs)-derived keratinocytes on it was evaluated in vitro and in vivo. It was expected that fabricated hybrid construct could promote wound healing due to its structure, physical, biological specifications. The fabricated fibrous mats were characterized for their structural, mechanical and biochemical properties. The shape uniformity and pore size of fibers showed smooth and homogenous structures of them. Fourier transform infrared spectroscopy (FTIR) verified all typical absorption characteristics of Ch-PVA + Silk polymers as well as Ch-PVA or pure PVA substrates. The contact angle and wettability measurement of fibers showed that mats found moderate hydrophilicity by addition of Ch and silk substrates compared with PVA alone. The mechanical features of Ch-PVA + Silk fibrous mat increase significantly through co-electrospun process as well as hybridization of these synthetic and natural polymers. Higher degrees of cellular attachment and proliferation obtained on Ch-PVA + Silk fibers compared with PVA and Ch-PVA fibers. In terms of the capability of Ch-PVA + Silk fibers and MSC-derived keratinocytes, histological analysis and skin regeneration results showed this novel fibrous construct could be suggested as a skin substitute in the repair of injured skin and regenerative medicine applications.


2010 ◽  
Vol 46 (3) ◽  
pp. 463-471 ◽  
Author(s):  
Ashlesha Pravin Pandit ◽  
Rajendra Dattatray Shinde

Blends of aqueous dispersion of a hydrophobic and hydrophilic polymer, namely Surelease®: hydroxypropyl methylcellulose (Surelease®: HPMC E15) were used as coating materials to control the drug release from coated pellets of the highly water soluble drug metoprolol succinate. Varying the polymer blends, ranges of drug release patterns were obtained at pH 6.8. The present study dealt with diffusion of drug through plasticized Surelease®/ hydroxypropyl methylcellulose (HPMC E15) films prepared by coating of drug and polymers onto non-pareil seeds using the solution layering technique. The release of metoprolol succinate from coated pellets was decreased with increased coating load of polymer. The optimized formulation was obtained by 3² full factorial design. The release profile revealed that the optimized formulation follows zero order release kinetics. The stability data showed no interaction for storage at 25ºC and 60% relative humidity.


2020 ◽  
Author(s):  
Afshin Fathi ◽  
Mehdi Khanmohammadi ◽  
Arash Goodarzi ◽  
Zahra Taherian Mobarakeh ◽  
Jamileh Saremi ◽  
...  

Abstract Hybrid fibrous mat containing cell interactive molecules offers the ability to deliver the cells and drugs in wound bed, which will help to achieve a high therapeutic treatment. In this study, a co-electrospun hybrid of polyvinyl alcohol (PVA), chitosan (Ch) and silk fibrous mat was developed and their wound healing potential by localizing bone marrow mesenchymal stem cells (MSCs)-derived keratinocytes on it was evaluated in vitro and in vivo. The fabricated fibrous Ch-PVA + Silk hydrogels were characterized for their structural, mechanical and biochemical properties. The shape uniformity and pore size of fibers showed smooth and homogenous structures of them. Fourier transform infrared spectroscopy (FTIR) verified all typical absorption characteristics of Ch-PVA + Silk polymers as well as Ch-PVA or pure PVA substrates. The contact angle and wettability measurement of fibers showed that mats found moderate hydrophilicity by addition of Ch and silk substrates compared with PVA alone. The mechanical features of Ch-PVA + Silk fibrous mats increase significantly through co-electrospun process as well as hybridization of these synthetic and natural polymers. Higher degrees of cellular attachment and proliferation obtained on Ch-PVA + Silk fibers compared with PVA and Ch-PVA fibers. In terms of the capability of Ch-PVA + Silk fibers and MSC-derived keratinocytes, histological analysis and skin regeneration results showed this novel fibrous construct could be suggested as a skin substitute in the repair of injured skin and regenerative medicine applications.


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