Monthly Archives: December 2015

PCL-PEG electrospun mesh investigated for scaffold treatment of damaged periodontal ligament

PolySciTech Division of Akina, Inc. (www.polyscitech.com) provides a wide array of block copolymers including PCL-PEG copolymers. One means of processing these polymers is using electrospinning. Electrospinning is a manufacturing technique based on applying a highly charged polymer solution onto a grounded metal collector. When this is done under the right conditions the polymer forms into an open mesh similar to woven fabric but with no particular weave pattern hence it is sometimes refered to as ‘non-woven.’ All the empty spaces in the micron scale work well for cell-permeation and so this is a popular technique for generating a tissue scaffold to help with guided tissue regeneration (GTR). The drawback to this technique is that the scaffold is somewhat generic and does not typically serve for regrowth of tissue which has a particular orientation to it. For example, the periodontal ligament tissue, which connects the jaw-bone to the root surface of teeth must be formed in a particular arrangement for it to hold everything in place the way it should. Recently, researchers electrospun PCL-PEG-PCL triblock polymer into sheets and then compressed together with a chitosan based ‘glue’ to form a tissue scaffold. This scaffold worked well to regenerate this oriented tissue both in-vitro and in vivo. Read more: Jiang, Wenlu, Long Li, Ding Zhang, Shishu Huang, Zheng Jing, Yeke Wu, Zhihe Zhao, Lixing Zhao, and Shaobing Zhou. “Incorporation of aligned PCL–PEG nanofibers into porous chitosan scaffolds improved the orientation of collagen fibers in regenerated periodontium.” Acta biomaterialia 25 (2015): 240-252. http://www.sciencedirect.com/science/article/pii/S1742706115300210

“Abstract: The periodontal ligament (PDL) is a group of highly aligned and organized connective tissue fibers that intervenes between the root surface and the alveolar bone. The unique architecture is essential for the specific physiological functionalities of periodontium. The regeneration of periodontium has been extensively studied by researchers, but very few of them pay attention to the alignment of PDL fibers as well as its functionalities. In this study, we fabricated a three-dimensional multilayered scaffold by embedding highly aligned biodegradable poly (ε-caprolactone)-poly(ethylene glycol) (PCE) copolymer electrospun nanofibrous mats into porous chitosan (CHI) to provide topographic cues and guide the oriented regeneration of periodontal tissue. In vitro, compared with random group and porous control, aligned nanofibers embedded scaffold could guide oriented arrangement and elongation of cells with promoted infiltration, viability and increased periodontal ligament-related genes expression. In vivo, aligned nanofibers embedded scaffold showed more organized arrangement of regenerated PDL nearly perpendicular against the root surface with more extensive formation of mature collagen fibers than random group and porous control. Moreover, higher expression level of periostin and more significant formation of tooth-supporting mineralized tissue were presented in the regenerated periodontium of aligned scaffold group. Incorporation of aligned PCE nanofibers into porous CHI proved to be applicable for oriented regeneration of periodontium, which might be further utilized in regeneration of a wide variety of human tissues with a specialized direction. Statement of Significance: The regeneration of periodontium has been extensively studied by researchers, but very few of them give attention to the alignment of periodontal ligament (PDL) fibers as well as its functionalities. The key issue is to provide guidance to the orientation of cells with aligned arrangement of collagen fibers perpendicular against the root surface. This study aimed to promote oriented regeneration of periodontium by structural mimicking of scaffolds. The in vitro and in vivo performances of the scaffolds were further evaluated to test the topographic-guiding and periodontium healing potentials. We also think our research may provide ideas in regeneration of a wide variety of human tissues with a specialized direction. Keywords: Periodontal tissue engineering; Biomimetics; Electrospun scaffold; Oriented regeneration; Periodontal ligament”

PLGA-FITC from PolySciTech used for development of Cromolyn delivery system

PolySciTech division of Akina, Inc (www.polyscitech.com) provides a wide array of biodegradable polymers. One of the materials which has great use for research and development is FITC end-capped PLGA. This has no particular pharmacological effect, but it makes the polymer fluorescent in that when a blue light (~490 nm) is shined onto the polymer it emits out a green light (~525 nm). This is handy for microscopy applications and other uses where tracking the location of the polymer in a complex system is important. Recently, a research group at the Indian Institute of Technology utilized PolySciTech PLGA-FITC to create a nanoparticle system to improve the oral bioavailability of cromolyn, a drug used for treatment of asthma and various allergic reactions. The use of PLGA-FITC allowed the researchers to track the location of the nanoparticles as they permeated through the intestinal lining in both in-vitro and animal models. Read more: Patel, Ravi R., Sundeep Chaurasia, Gayasuddin Khan, Pramila Chaubey, Nagendra Kumar, and Brahmeshwar Mishra. “Cromolyn Sodium Encapsulated PLGA Nanoparticles: An Attempt to Improve Intestinal Permeation.” International Journal of Biological Macromolecules (2015). http://www.sciencedirect.com/science/article/pii/S0141813015301823

“Abstract: High hydrophilicity curtails the intestinal permeation of cromolyn sodium (CS) which in turn compels to compromise with its multiple biological activities. Hence, the present research was intended with an objective to develop CS encapsulated polylactide-co-glycolide (PLGA) nanoparticles (CS-PNs) for enhancing intestinal permeation. The CS-PNs were prepared by double emulsification solvent evaporation method (W1/O/W2). The “Quality by Design” approach using box-behnken experimental design was employed to enhance encapsulation of CS inside CS-PNs without compromising with particle size. The polymer concentration, surfactant concentration and organic/aqueous phase ratio significantly affected the physicochemical properties of CS-PNs. The optimized CS-PNs were subjected to various solid-state and surface characterization studies using FTIR, DSC, XRD, TEM and AFM, which pointed towards the encapsulation of CS inside the spherical shaped nanoparticles without any physical as well as chemical interactions. Ex-vivo intestinal permeation study demonstrated ∼4 fold improvements in CS permeation by forming CS-PNs as compared to pure CS. Further, in-vivo intestinal uptake study performed using confocal microscopy, after oral administration confirmed the permeation potential of CS-PNs. Thus, the findings of the studies suggest that CS-PNs could provide a superior therapeutic carrier system of CS, with enhanced intestinal permeation. Keywords: Cromolyn sodium; PLGA nanoparticles; Intestinal permeation”

PLGA-PEG investigated for drug-delivery treatment of Leishmaniasis

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of PLGA-PEG block copolymers. Recently, these kinds of polymers were used to develop a nanoparticle system to deliver miltefosine to Leishmania donovani as a treatment of Leishmaniasis. Read more: Kumar, Rishikesh, Ganesh Chandra Sahoo, Krishna Pandey, V. N. R. Das, Roshan K. Topno, Md Yousuf Ansari, Sindhuprava Rana, and Pradeep Das. “Development of PLGA–PEG encapsulated miltefosine based drug delivery system against visceral leishmaniasis.” Materials Science and Engineering: C 59 (2016): 748-753. http://www.sciencedirect.com/science/article/pii/S0928493115305154

“Abstract: Targeted drug delivery systems are ideal technology to increase the maximum mechanism of action with smaller dose, we have developed miltefosine encapsulated PLGA–PEG nanoparticles (PPEM) to target macrophage of infected tissues against Leishmania donovani. The structural characterization of PLGA–PEG by transmission electron microscopy (TEM) has shown a size range of 10 to 15 nm. Synthesis and drug encapsulation confirmed by dynamic light scattering (DLS) and Fourier transform infrared spectroscopy (FTIR) and confirmed NP encapsulation. The dose of nano encapsulated miltefosine decreased by fifty percent as compared to that of a conventional miltefosine and Amphoterecin B. The inhibition of amastigotes in the splenic tissue with nano encapsulated miltefosine (23.21 ± 23) was significantly more than the conventional miltefosine (89.22 ± 52.7) and Amphoterecin B (94.12 ± 55.1). This study signifies that there is an increased contact surface area of the nano encapsulated drug and significant reduction in size, improved the efficacy in both in vitro and in vivo study than that of the conventional miltefosine, Amphoterecin B. Graphical abstract: The analyses of detailed structure characterized by TEM and DLS confirmed the nano-size of the particle 10–20 nm and FTIR confirmed for antileishmanial drug encapsulation in to PLGA–PEG. The dose of miltefosine is decreased by fifty percent as the IC50 value is decreased from 0.2 to 0.1 μg. Further inhibitions of amastigotes in the splenic tissue with these nanoparticles are significantly more than the conventional miltefosine and PLGA–PEG encapsulated Amphoterecin B (23.21 ± 23/89.09 ± 52.7/92.12 ± 55.1). Keywords: Miltefosine; Transmission electron microscope; Nanoscale; Amastigotes; Amphoterecin B”

Chitosan-Fluorescein used for investigating targeted muco-adhesive drug-delivery to fish

Chitosan is a readily available biomaterial chemically derived from chitin which comprises crab-shells and other biological sources. This amino-polysaccharide has many interesting properties including biodegradability, biocompatibility, an inherent resistance towards bacteria, and muco-adhesion. Recently, researchers in Brazil utilized Fluorescein conjugated chitosan to track nanoparticles as they utilized them for delivery of medicines to fish in order to minimize aquatic disease. Similar, fluorescently conjugated chitosans, are available from PolySciTech division of Akina, Inc under the Kitopure brand line (https://akinainc.com/polyscitech/products/Kitopure/index.php, e.g. Kito-8 and Kito-9).  Read more about the recent aquatic drug-delivery research here: Costa, AC da S., H. M. Brandao, S. R. Silva, A. R. Bentes‐Sousa, J. A. P. Diniz, J. de J. Viana Pinheiro, M. de FC Melo, J. O. C. Silva, E. R. Matos, and R. M. Ribeiro‐Costa. “Mucoadhesive nanoparticles: a new perspective for fish drug application.” Journal of fish diseases (2015). http://onlinelibrary.wiley.com/doi/10.1111/jfd.12373/full

PLGA-PEG-Maleimide used for targeted treatment of heart disease

When one refers to ‘targeted treatment’ or ‘targeted drug delivery’ the typical assumption is that the treatment is targeted towards cancer cells. This is, indeed, a very widely used application of these techniques, however it is not the only one. One of the primary contributing factors to heart disease is a pathological local inflammatory response which leads to white-blood-cell invasion of and subsequent thickening/hardening of arterial walls. Recently this has been sought as a manner to treat heart disease in addition to conventional therapies such as cholesterol lowering statins, etc. One manner to treat this is the localized delivery of pro-resolving peptide mediators such as Ac2-26, which binds to GPCR to effect a powerful anti-inflammatory response that reduces oxidative stress and plaque necrosis. Recently, researchers used PLGA-PEG-Maleimide to create a collagen IV targeted nanoparticle for the localized delivery of Ac2-26 anti-inflammatory peptide to atherosclerotic lesions. Testing in mouse models showed promise for this method of treatment. PLGA-PEG-Maleimide is one of the many activated precursor polymers available from PolySciTech Division of Akina, Inc (www.polyscitech.com). Read more about the research here: Fredman, Gabrielle, Nazila Kamaly, Stefano Spolitu, Jaclyn Milton, Devram Ghorpade, Raymond Chiasson, George Kuriakose, Mauro Perretti, Omid Farokzhad, and Ira Tabas. “Targeted nanoparticles containing the proresolving peptide Ac2-26 protect against advanced atherosclerosis in hypercholesterolemic mice.” Science translational medicine 7, no. 275 (2015): 275ra20-275ra20. Fulltext: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397585/

“Abstract: Chronic, nonresolving inflammation is a critical factor in the clinical progression of advanced atherosclerotic lesions. In the normal inflammatory response, resolution is mediated by several agonists, among which is the glucocorticoid-regulated protein called annexin A1. The proresolving actions of annexin A1, which are mediated through its receptor N-formyl peptide receptor 2 (FPR2/ALX), can be mimicked by an amino-terminal peptide encompassing amino acids 2–26 (Ac2-26). Collagen IV (Col IV)–targeted nanoparticles (NPs) containing Ac2-26 were evaluated for their therapeutic effect on chronic, advanced atherosclerosis in fat-fed Ldlr−/− mice. When administered to mice with preexisting lesions, Col IV–Ac2-26 NPs were targeted to lesions and led to a marked improvement in key advanced plaque properties, including an increase in the protective collagen layer overlying lesions (which was associated with a decrease in lesional collagenase activity), suppression of oxidative stress, and a decrease in plaque necrosis. In mice lacking FPR2/ALX in myeloid cells, these improvements were not seen. Thus, administration of a resolution-mediating peptide in a targeted NP activates its receptor on myeloid cells to stabilize advanced atherosclerotic lesions. These findings support the concept that defective inflammation resolution plays a role in advanced atherosclerosis, and suggest a new form of therapy.”