Chitosan/Pluronic F127 Thermosensitive Hydrogel as an Injectable Dexamethasone Delivery Carrier

Intra-articular administration of anti-inflammatory drugs is a strategy that allows localized action on damaged articular cartilage and reduces the side effects associated with systemic drug administration. The objective of this work is to prepare injectable thermosensitive hydrogels for the long-term application of dexamethasone. The hydrogels were prepared by mixing chitosan (CS) and Pluronic-F127 (PF) physically. In addition, tripolyphosphate (TPP) was used as a crosslinking agent. Chitosan added to the mix increased the gel time compared to the pluronic gel alone. The incorporation of TPP into the material modified the morphology of the hydrogels formed. Subsequently, MTS and Live/Dead® experiments were performed to investigate the toxicity of hydrogels against human chondrocytes. The in vitro releases of dexamethasone (DMT) from CS-PF and CS-PF-TPP gels had an initial burst and took more time than that from the PF hydrogel. In vivo studies showed that hydrogels retained the fluorescent compound longer in the joint than when administered in PBS alone. These results suggest that the CS-PF and CS-PF-TPP hydrogels loaded with DMT could be a promising drug delivery platform for the treatment of osteoarthritis.

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Renal effects induced by prolonged mPGES1 inhibition

AJP Renal Physiology ◽

10.1152/ajprenal.00492.2013 ◽

2014 ◽

Vol 306 (1) ◽

pp. F68-F74 ◽

Cited By ~ 10

Author(s):

Francisco Salazar ◽

Michael L. Vazquez ◽

Jaime L. Masferrer ◽

Gabriel Mbalaviele ◽

Maria T. Llinas ◽

...

Keyword(s):

Renal Function ◽

Plasma Renin ◽

In Vivo Studies ◽

Renal Effects ◽

Excretory Function ◽

Membrane Bound ◽

Inflammatory Drugs ◽

Chronically Instrumented Dogs

The importance of membrane-bound PGE synthase 1 (mPGES1) in the regulation of renal function has been examined in mPGES1-deficient mice or by evaluating changes in its expression. However, it is unknown whether prolonged mPGES1 inhibition induces significant changes of renal function when Na+ intake is normal or low. This study examined the renal effects elicited by a selective mPGES1 inhibitor (PF-458) during 7 days in conscious chronically instrumented dogs with normal Na+ intake (NSI) or low Na+ intake (LSI). Results obtained in both in vitro and in vivo studies have strongly suggested that PF-458 is a selective mPGES1 inhibitor. The administration of 2.4 mg·kg−1·day−1 PF-458 to dogs with LSI did not induce significant changes in renal blood flow (RBF) and glomerular filtration rate (GFR). A larger dose of PF-458 (9.6 mg·kg−1·day−1) reduced RBF ( P < 0.05) but not GFR in dogs with LSI and did not induce changes of renal hemodynamic in dogs with NSI. Both doses of PF-458 elicited a decrease ( P < 0.05) in PGE2 and an increase ( P < 0.05) in 6-keto-PGF1α. The administration of PF-458 did not induce significant changes in renal excretory function, plasma renin activity, and plasma aldosterone and thromboxane B2 concentrations in dogs with LSI or NSI. The results obtained suggest that mPGES1 is involved in the regulation of RBF when Na+ intake is low and that the renal effects elicited by mPGES1 inhibition are modulated by a compensatory increment in PGI2. These results may have some therapeutical implications since it has been shown that prolonged mPGES1 inhibition has lower renal effects than those elicited by nonsteroidal anti-inflammatory drugs or selective cyclooxygenase-2 inhibitors.

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A Mixed Thermosensitive Hydrogel System for Sustained Delivery of Tacrolimus for Immunosuppressive Therapy

Pharmaceutics ◽

10.3390/pharmaceutics11080413 ◽

2019 ◽

Vol 11 (8) ◽

pp. 413 ◽

Cited By ~ 3

Author(s):

Hsiu-Chao Lin ◽

Madonna Rica Anggelia ◽

Chih-Chi Cheng ◽

Kuan-Lin Ku ◽

Hui-Yun Cheng ◽

...

Keyword(s):

Immunosuppressive Therapy ◽

In Vitro Release ◽

Aqueous Solubility ◽

Immunosuppressive Agent ◽

Sustained Delivery ◽

Thermosensitive Hydrogel ◽

Thermosensitive Hydrogels ◽

Hydrogel System

Tacrolimus is an immunosuppressive agent for acute rejection after allotransplantation. However, the low aqueous solubility of tacrolimus poses difficulties in formulating an injection dosage. Polypeptide thermosensitive hydrogels can maintain a sustained release depot to deliver tacrolimus. The copolymers, which consist of poloxamer and poly(l-alanine) with l-lysine segments at both ends (P–Lys–Ala–PLX), are able to carry tacrolimus in an in situ gelled form with acceptable biocompatibility, biodegradability, and low gelling concentrations from 3 to 7 wt %. By adding Pluronic F-127 to formulate a mixed hydrogel system, the drug release rate can be adjusted to maintain suitable drug levels in animals with transplants. Under this formulation, the in vitro release of tacrolimus was stable for more than 100 days, while in vivo release of tacrolimus in mouse model showed that rejection from skin allotransplantation was prevented for at least three weeks with one single administration. Using these mixed hydrogel systems for sustaining delivery of tacrolimus demonstrates advancement in immunosuppressive therapy.

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Hemoglobin Polymerized with a Naturally Occurring Crosslinking Agent as a Blood Substitute: In Vitro and In Vivo Studies

Artificial Cells Blood Substitutes and Biotechnology ◽

10.1081/bio-120037830 ◽

2004 ◽

Vol 32 (2) ◽

pp. 243-262 ◽

Cited By ~ 11

Author(s):

Wen-Hsiang Chang ◽

Yen Chang ◽

Yi-Chien Chen ◽

Hsing-Wen Sung

Keyword(s):

Crosslinking Agent ◽

Blood Substitute ◽

In Vivo Studies ◽

Naturally Occurring

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A mucoadhesive thermosensitive hydrogel containing erythropoietin as a potential treatment in oral mucositis: in vitro and in vivo studies

Drug Delivery and Translational Research ◽

10.1007/s13346-018-0566-9 ◽

2018 ◽

Vol 8 (5) ◽

pp. 1226-1237 ◽

Cited By ~ 4

Author(s):

Mahboubeh Rezazadeh ◽

Niloofar Jafari ◽

Vajihe Akbari ◽

Marjan Amirian ◽

Majid Tabbakhian ◽

...

Keyword(s):

Oral Mucositis ◽

In Vivo Studies ◽

Potential Treatment ◽

Thermosensitive Hydrogel

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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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Impact of anesthesia and analgesia techniques on glioblastoma progression. A narrative review

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa123 ◽

2020 ◽

Vol 2 (1) ◽

Author(s):

Ann Privorotskiy ◽

Shreyas P Bhavsar ◽

Frederick F Lang ◽

Jian Hu ◽

Juan P Cata

Keyword(s):

Patient Outcomes ◽

Clinical Studies ◽

Narrative Review ◽

In Vivo Studies ◽

General Anesthetics ◽

Anesthetic Care ◽

Inflammatory Drugs ◽

Cox 2 Inhibitors

Abstract Glioblastoma (GBM) is an aggressive malignant CNS tumor with a median survival of 15 months after diagnosis. Standard therapy for GBM includes surgical resection, radiation, and temozolomide. Recently, anesthetics and analgesics have received attention for their potential involvement in mediating tumor growth. This narrative review investigated whether various members of the 2 aforementioned classes of drugs have a definitive impact on GBM progression by summarizing pertinent in vitro, in vivo, and clinical studies. Recent publications regarding general anesthetics have been inconsistent, showing that they can be pro-tumoral or antitumoral depending on the experimental context. The local anesthetic lidocaine has shown consistent antitumoral effects in vitro. Clinical studies looking at anesthetics have not concluded that their use improves patient outcomes. In vitro and in vivo studies looking at opioid involvement in GBM have demonstrated inconsistent findings regarding whether these drugs are pro-tumoral or antitumoral. Nonsteroidal anti-inflammatory drugs, and specifically COX-2 inhibitors, have shown inconsistent findings across multiple studies looking at whether they are beneficial in halting GBM progression. Until multiple repeatable studies show that anesthetics and analgesics can suppress GBM growth, there is no strong evidence to recommend changes in the anesthetic care of these patients.

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