In situ gelling systems based on Pluronic F127/Pluronic F68 formulations for ocular drug delivery

Khateb, Kosai Al; Ozhmukhametova, Elvira K.; Mussin, Marat N.; Seilkhanov, Serzhan K.; Rakhypbekov, Tolebai K.; Lau, Wing Man; Khutoryanskiy, Vitaliy V.

doi:10.1016/j.ijpharm.2016.02.027

Cited by 230 publications

(148 citation statements)

References 37 publications

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“…By comparison between the results of in vitro and in vivo evaluations on GEL1 and GEL2, it could be rationally concluded that relative hydrophilic formulation led to faster hydrogel erosion, drug release and intravaginal elimination. Our finding is also consistent with a recently published study on ocular administration, which revealed that, under a fixed total polymer concentration, higher content of hydrophilic poloxamer 188 in the formulation resulted in faster removal from the corneal surface after application 28 . These phenomena could be explained by Marchetti group׳s work 29 , in which the authors found that the presence of hydrophilic additives like polyethylene glycol accelerated drug release from poloxamer-based hydrogel even at low concentration, and attributed the accelerated release to the higher osmotic pressure between the hydrogel and the dissolution medium created by the increased hydrogel hydrophilicity.…”

Section: Resultssupporting

confidence: 93%

In vivo retention of poloxamer-based in situ hydrogels for vaginal application in mouse and rat models

Liu

Yang

Feng

et al. 2017

Acta Pharmaceutica Sinica B

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The purpose of this study is to evaluate the in vivo retention capabilities of poloxamer-based in situ hydrogels for vaginal application with nonoxinol-9 as the model drug. Two in situ hydrogel formulations, which contained 18% poloxamer 407 plus 1% poloxamer 188 (GEL1, relative hydrophobic) or 6% poloxamer 188 (GEL2, relative hydrophilic), were compared with respect to the rheological properties, in vitro hydrogel erosion and drug release. The vaginal retention capabilities of these hydrogel formulations were further determined in two small animal models, including drug quantitation of vaginal rinsing fluid in mice and isotope tracing with 99mTc in rats. The two formulations exhibited similar phase transition temperatures ranging from 27 to 32 °C. Increasing the content of poloxamer 188 resulted in higher rheological moduli under body temperature, but slightly accelerated hydrogel erosion and drug release. When compared in vivo, GEL1 was eliminated significantly slower in rat vagina than GEL2, while the vaginal retention of these two hydrogel formulations behaved similarly in mice. In conclusion, increases in the hydrophilic content of formulations led to faster hydrogel erosion, drug release and intravaginal elimination. Rats appear to be a better animal model than mice to evaluate the in situ hydrogel for vaginal application.

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Section: Resultssupporting

confidence: 93%

In vivo retention of poloxamer-based in situ hydrogels for vaginal application in mouse and rat models

Liu

Yang

Feng

et al. 2017

Acta Pharmaceutica Sinica B

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“…[25][26][27] Our research group has previously synthesized a family of PBCs based on the amphiphilic Pluronic F127 triblock copolymer. [25][26][27] Our research group has previously synthesized a family of PBCs based on the amphiphilic Pluronic F127 triblock copolymer.…”

Section: Discussionmentioning

confidence: 99%

Safety and biocompatibility of injectable vaccine adjuvants composed of thermogelling block copolymer gels

Adams

Senapati

Haughney

et al. 2019

J Biomedical Materials Res

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Injectable thermogelling polymers have been recently investigated as novel adjuvants and delivery systems for next generation vaccines. As research into natural and synthetic biocompatible polymers progresses, the safety and biocompatibility of these compounds is of paramount importance. We have developed cationic pentablock copolymer (PBC) vaccine adjuvants based on Pluronic F127, a thermogelling triblock copolymer that has been approved by the FDA for multiple applications, and methacrylated poly(diethyl amino)ethyl methacrylate outer blocks. These novel materials have been demonstrated to effectively create an antigen depot, minimally impact antigen stability, and enhance the immune response to antigens (i.e., adjuvanticity) in mice. In this work, we investigated the safety and biocompatibility of the parent triblock Pluronic gels and the cationic PBC gels in mice. Histological analysis showed no injection site reactions and no damage to the liver or kidneys was observed upon administering the block copolymer formulations. However, the subcutaneous injection of a thermogelling Pluronic solution induced increased levels of lipids in the blood, with no further deleterious effects observed from the addition of the cationic outer blocks. This hyperlipidemia resolved within 30 days after the administration of the Pluronic formulation. To mitigate this adverse effect, the vaccine adjuvant formulations were modified by adding poly(vinyl alcohol), which allowed gelation, while reducing the amount of Pluronic in the formulation. This modified formulation abrogated the observed hyperlipidemia and no adverse effects were observed in the serum through biomarker analysis or at the injection site (i.e., inflammation) in comparison to the responses induced by administration of saline or incomplete Freund's adjuvant. These studies provide a foundation to developing these gels as adjuvants for next generation vaccines. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1754–1762, 2019.

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“…Also, KT has been used in form of hydrogel for nasal delivery using poloxamer 407 and carrageenan More recently, ofloxacin loaded Pluronic F127 and Pluronic F68 (20% w/v) in situ gelling formulation have been prepared and characterised. These deemed promising ocular formulation due to prolonged pre-corneal retention and good ocular tolerability using slug mucosal irritation assay and bovine corneal erosion study (Al Khateb et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations: Design, characterisation, toxicity and transcorneal permeation studies

Fathalla

Vangala

Longman

et al. 2017

European Journal of Pharmaceutics and Biopharmaceutics

142

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, Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations: Design, characterisation, toxicity and transcorneal permeation studies, European Journal of Pharmaceutics and Biopharmaceutics (2017), doi: http://dx.doi.org/10. 1016/j.ejpb.2017.01.008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractThis study was aimed at preparing, characterising and evaluating in situ gel formulations based on a blend of two hydrophilic polymers i.e. poloxamer 407 (P407) and poloxamer 188 (P188) for a sustained ocular delivery of ketorolac tromethamine (KT). Drug-polymer interaction studies were performed using DSC and FT-IR. The gelation temperature (T sol-gel ), gelation time, rheological behaviour, mucoadhesive characteristics of these gels, transcorneal permeation and ocular irritation as well as toxicity was investigated. DSC and FT-IR studies revealed that there may be electrostatic interactions between the drug and the polymers used.P188 modified the T sol/gel of P407 bringing it close to eye temperature (35 o C) compared with the formulation containing P407 alone. Moreover, gels that comprised P407 and P188 exhibited a pseudoplastic behaviour at different concentrations. Furthermore, mucoadhesion study using mucin discs showed that in situ gel formulations have good mucoadhesive characteristics upon increasing the concentration of P407. When comparing formulations PP11 and PP12, the work of adhesion decreased significantly (P < 0.001) from 377.9 ± 7.79 mN.mm to 272.3 ± 6.11 mN.mm. In vitro release and ex vivo permeation experiments indicated that the in situ gels were able to prolong and control KT release as only 48% of the KT released within 12 h. In addition, the HET-CAM and BCOP tests confirmed the nonirritancy of KT loaded in situ gels, and HET-CAM test demonstrated the ability of ocular protection against strongly irritant substances. MTT assay on primary corneal epithelial cells revealed that in situ gel formulations loaded with KT showed reasonable and acceptable percent cell viability compared with control samples.

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In situ gelling systems based on Pluronic F127/Pluronic F68 formulations for ocular drug delivery

Cited by 230 publications

References 37 publications

In vivo retention of poloxamer-based in situ hydrogels for vaginal application in mouse and rat models

In vivo retention of poloxamer-based in situ hydrogels for vaginal application in mouse and rat models

Safety and biocompatibility of injectable vaccine adjuvants composed of thermogelling block copolymer gels

Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations: Design, characterisation, toxicity and transcorneal permeation studies

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