scholarly journals Synthesis of novel polymeric nanoparticles (methoxy-polyethylene glycol-chitosan/hyaluronic acid) containing 7-ethyl-10-hydroxycamptothecin for colon cancer therapy: in vitro, ex vivo and in vivo investigation

2021 ◽  
Vol 49 (1) ◽  
pp. 367-380
Author(s):  
Faezeh Sharifi ◽  
Mansour Jahangiri ◽  
Pedram Ebrahimnejad
Keyword(s):  
Colon Cancer ◽  
Hyaluronic Acid ◽  
Polyethylene Glycol ◽  
Cancer Therapy ◽  
Ex Vivo ◽  
Polymeric Nanoparticles ◽  
Glycol Chitosan ◽  
Methoxy Polyethylene Glycol

scholarly journals How Can Biomolecules Improve Mucoadhesion of Oral Insulin? A Comprehensive Insight using Ex-Vivo, In Silico, and In Vivo Models

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 675 ◽  
Author(s):  
Mariana Amaral ◽  
Ana Sofia Martins ◽  
José Catarino ◽  
Pedro Faísca ◽  
Pradeep Kumar ◽  
...  
Keyword(s):  
In Silico ◽  
Ex Vivo ◽  
Polymeric Nanoparticles ◽  
Spherical Shape ◽  
Diabetic Rats ◽  
Laser Scattering ◽  
In Vivo Models ◽  
Mean Size

Currently, insulin can only be administered through the subcutaneous route. Due to the flaws associated with this route, it is of interest to orally deliver this drug. However, insulin delivered orally has several barriers to overcome as it is degraded by the stomach’s low pH, enzymatic content, and poor absorption in the gastrointestinal tract. Polymers with marine source like chitosan are commonly used in nanotechnology and drug delivery due to their biocompatibility and special features. This work focuses on the preparation and characterization of mucoadhesive insulin-loaded polymeric nanoparticles. Results showed a suitable mean size for oral administration (<600 nm by dynamic laser scattering), spherical shape, encapsulation efficiency (59.8%), and high recovery yield (80.6%). Circular dichroism spectroscopy demonstrated that protein retained its secondary structure after encapsulation. Moreover, the mucoadhesive potential of the nanoparticles was assessed in silico and the results, corroborated with ex-vivo experiments, showed that using chitosan strongly increases mucoadhesion. Besides, in vitro and in vivo safety assessment of the final formulation were performed, showing no toxicity. Lastly, the insulin-loaded nanoparticles were effective in reducing diabetic rats’ glycemia. Overall, the coating of insulin-loaded nanoparticles with chitosan represents a potentially safe and promising approach to protect insulin and enhance peroral delivery.

scholarly journals Hydrogel-Mediated DOX⋅HCl/PTX Delivery System for Breast Cancer Therapy

2019 ◽  
Vol 20 (19) ◽  
pp. 4671
Author(s):  
Hoon Hyun ◽  
Young Yoo ◽  
So Kim ◽  
Hyun Ko ◽  
Heung Chun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Anticancer Effect ◽  
Breast Cancer Therapy ◽  
Glycol Chitosan ◽  
Burst Period ◽  
Delivery Approach ◽  
Dual Drug

We used a hydrogel-mediated dual drug delivery approach, based on an injectable glycol chitosan (GC) hydrogel, doxorubicin hydrochloride (DOX⋅HCl), and a complex of beta-cyclodextrin (β-CD) and paclitaxel (PTX) (GDCP) for breast cancer therapy in vitro and in vivo. The hydrogel was swollen over 3 days and remained so thereafter. After an initial burst period of 7 hours, the two drugs were released in a sustained manner for 7 days. The in vitro cell viability test showed that GDCP had a better anticancer effect than well plate and DOX⋅HCl/PTX (DP). In addition, the in vivo tests, which evaluated the anticancer effect, systemic toxicity, and histology, proved the feasibility of GDCP as a clinical therapy for breast cancer.

scholarly journals Controlled Release of Strontium through Neutralization Reaction within a Methoxy(Polyethylene Glycol)-Polyesterc hydrogel

2017 ◽  
Vol 15 (2) ◽  
pp. 162-169 ◽  
Author(s):  
Sydney Peng ◽  
Zhi-Teng Lai ◽  
Ding-Wei Hong ◽  
I-Ming Chu ◽  
Po-Liang Lai
Keyword(s):  
Polyethylene Glycol ◽  
Glycolic Acid ◽  
Time Frame ◽  
Neutralization Reaction ◽  
Bone Void Filler ◽  
Potential Acid ◽  
Methoxy Polyethylene Glycol ◽  
Localized Treatment

Background The aim of this study was to develop a minimally invasive hydrogel system that can release strontium ions, an element that has been shown to increase osteoblast proliferation and prohibit bone resorption, in a controlled manner. Methods SrCO3 was selected as the salt of choice due to potential acid neutralization reaction between SrCO3 and degradation by-products of methoxy(polyethylene glycol)- co-poly(lactic- co-glycolic acid) (mPEG-PLGA): namely, lactic acid and glycolic acid. SrCO3 was incorporated into mPEG-PLGA hydrogel, and the system was assessed for gelation properties, drug release and biocompatibility. Results SrCO3 incorporation at hydrogel to SrCO3 ratios of 5:1, 3:1 and 1:1 (wt%) did not compromise the thermosensitivity of mPEG-PLGA hydrogels. Furthermore, incorporation of SrCO3 at 1:1 ratio prevented copolymer self-catalysis and decreased hydrogel weight loss from 85% to 61% in vitro after 30 days. During the 30-day time frame, zero-order strontium release was observed and was correlated to hydrogel degradation and acidity. The addition of SrCO3 also improved in vivo hydrogel biocompatibility, due to moderation of acidic microenvironment and amelioration of inflammatory response. Conclusions These results showed that the described system is suitable for the extended release of strontium and exhibits potential for localized treatment for osteoporosis or as a bone void filler.

scholarly journals Formulation and Evaluation of Thermosensitive Biogels for Nose to Brain Delivery of Doxepin

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Anuja Naik ◽  
Hema Nair
Keyword(s):  
Polyethylene Glycol ◽  
Intranasal Administration ◽  
Ex Vivo ◽  
Forced Swim Test ◽  
Brain Delivery ◽  
Pharmacodynamic Parameter ◽  
Swim Test ◽  
Local Toxicity

Thermoreversible biogels can serve as effective systems for delivery of drugs through nose with increased nasal residence time. The objective of this study was to use chitosan and glycerophosphate based thermoreversible systems for delivery of doxepin to brain through intranasal administration. Formulations were prepared by admixture of suitable dilutions of chitosan and glycerophosphate with or without polyethylene glycol, followed by addition of the antidepressant doxepin hydrochloride. Both systems were evaluated for gelling characteristics, rheology, mucoadhesion,in vitrorelease, andex vivopermeation through sheep nasal mucosa.In vivoefficacy was evaluated in Swiss albino mice through the forced swim test. Nasal tissues of mice subjected to repeated exposure to formulation were evaluated histopathologically. Both formulations gelled rapidly at 37°C, returned to sol state on cooling, and exhibited thixotropy. Addition of polyethylene glycol decreased the glycerophosphate content required for gelation and rendered the formulation isotonic. Both gels showed good mucoadhesion, enhanced drug permeation, and provided prolongedin vitrorelease at 37°C. Efficacy of the formulation in treated groups was inferred from the measured pharmacodynamic parameter and histopathological reports of formulation treated groups showed no significant local toxicity. The biogels could be potential systems for effective drug delivery to brain via nose.

scholarly journals STEM-28. NANOPARTICLES ENCAPSULATING A CONNEXIN43 MIMETIC PEPTIDE LIMIT GLIOMA STEM CELL SURVIVAL AND GLIOBLASTOMA PROGRESSION

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii202-ii202
Author(s):  
John Will ◽  
Emily Thompson ◽  
Megan Harrigan ◽  
James Smyth ◽  
Zhi Sheng ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Ex Vivo ◽  
Polymeric Nanoparticles ◽  
Treatment Strategies ◽  
Chemotherapeutic Agents ◽  
Adult Brain ◽  
Cellular Heterogeneity ◽  
Mimetic Peptide

Abstract Glioblastoma (GBM) is the most common and aggressive primary adult brain tumor in the US. The current treatment regimen for GBM still retains an alarmingly poor prognosis, with median survival of only 14.6 months. Failure to generate more effective treatment strategies is due to the infiltrative nature of GBM tumor cells, which hinders complete surgical resection, and cellular heterogeneity within GBM tumors, with a sub-population of glioma stem cells (GSCs) resistant to irradiation treatment and chemotherapeutic agents including temozolomide. As a result, all treated GBM patients will experience tumor recurrence, highlighting the need for novel approaches in targeting such refractory tumor cell populations to successfully treat GBM tumors and prevent recurrence. Using super resolution localization microscopy, we have identified that increased interaction of connexin43 (Cx43) with microtubules in GSCs confers tumorigenic behavior to these cells. We employed a Cx43 mimetic peptide named JM2 (juxtamembrane 2) that encompasses the microtubule binding sequence of the Cx43 carboxy-terminus. This peptide drug efficiently and specifically disrupts the interaction of Cx43 with microtubules and limits GSC survival, proliferation, and migration, without affecting normal human astrocytes. Next, we implemented the therapeutic strategy of JM2 encapsulation within biodegradable polymeric nanoparticles (NPs) to reduce administration frequency and patient discomfort, and increase peptide stability and activity. We confirmed sustained release of JM2 from these poly(lactic-co-glycolic) acid biodegradable NPs, and JM2 bioactivity through disruption of Cx43 interaction with microtubules. Administration of JM2-NPs inhibits GSC-derived neurosphere formation in vitro and patient GBM-derived organoid growth ex vivo. Finally, using an orthotopic xenograft brain tumor mouse model, we demonstrate in vivo that JM2-NPs significantly decrease the number of GSCs within brain tumors, and inhibit the formation of highly invasive GBM tumors. Our findings on generation of JM2-NPs to target GSC survival lays the foundation for future clinical trials in newly diagnosed GBM patients.

scholarly journals In vitro and in vivo Study on an Injectable Glycol Chitosan/Dibenzaldehyde-Terminated Polyethylene Glycol Hydrogel in Repairing Articular Cartilage Defects

2021 ◽  
Vol 9 ◽  
Author(s):  
Jianhua Yang ◽  
Xiaoguang Jing ◽  
Zimin Wang ◽  
Xuejian Liu ◽  
Xiaofeng Zhu ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Polyethylene Glycol ◽  
Knee Joint ◽  
Cartilage Defect ◽  
Positive Control ◽  
Cartilage Defects ◽  
Control Group ◽  
Glycol Chitosan

The normal anatomical structure of articular cartilage determines its limited ability to regenerate and repair. Once damaged, it is difficult to repair it by itself. How to realize the regeneration and repair of articular cartilage has always been a big problem for clinicians and researchers. Here, we conducted a comprehensive analysis of the physical properties and cytocompatibility of hydrogels, and evaluated their feasibility as cell carriers for Adipose-derived mesenchymal stem cell (ADSC) transplantation. Concentration-matched hydrogels were co-cultured with ADSCs to confirm ADSC growth in the hydrogel and provide data supporting in vivo experiments, which comprised the hydrogel/ADSCs, pure-hydrogel, defect-placement, and positive-control groups. Rat models of articular cartilage defect in the knee joint region was generated, and each treatment was administered on the knee joint cartilage area for each group; in the positive-control group, the joint cavity was surgically opened, without inducing a cartilage defect. The reparative effect of injectable glycol chitosan/dibenzaldehyde-terminated polyethylene glycol (GCS/DF-PEG) hydrogel on injured articular cartilage was evaluated by measuring gross scores and histological score of knee joint articular-cartilage injury in rats after 8 weeks. The 1.5% GCS/2% DF-PEG hydrogels degraded quickly in vitro. Then, We perform in vivo and in vitro experiments to evaluate the feasibility of this material for cartilage repair in vivo and in vitro.

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