Sustained intravitreal delivery of dexamethasone using an injectable and biodegradable thermogel

Zhang, Li; Shen, Wen; Luan, Jiabin; Yang, Dongxiao; Wei, Gang; Yu, Lin; Lu, Weiyue; Ding, Jiandong

doi:10.1016/j.actbio.2015.05.005

Cited by 87 publications

(48 citation statements)

References 59 publications

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“…The SCo injection of voriconazole-thermogel was easily injected in the SCo space and was well tolerated by all the horses, with no evidence of ocular pain observed for up to 23 days. Safety of the technique and behavior of the thermogel were consistent with previous reports of SCo injections in horses and the use of copolymers in ophthalmology [10,24,[38][39][40][41]. Even though there was a significant increase in conjunctival swelling following SCo injection, a score of 2 is considered to be mild [29,30].…”

Section: Discussionsupporting

confidence: 83%

Sustained-release voriconazole-thermogel for subconjunctival injection in horses: ocular toxicity and in-vivo studies

et al. 2020

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Background: Keratomycosis is a relatively common, sight threatening condition in horses, where treatment is often prolonged and costly. Subconjunctival (SCo) injections offer less resistance to drug diffusion than the topical route, resulting in better penetration to the ocular anterior segment. Voriconazole, a second generation triazole antifungal, is effective against common fungal organisms causing keratomycosis. If combined with a thermogel biomaterial, voriconazole can be easily injected in the SCo space to provide sustained drug release. The purpose of this study was to evaluate the drug concentrations in the anterior segment and clinical effects after SCo injections of voriconazole-containing thermogel: poly (DL-lactide-co-glycolide-b-ethylene glycol-b-DL-lactide-co-glycolide) (PLGA-PEG-PLGA) in healthy equine eyes. Results: Voriconazole aqueous humor (AH) and tear concentrations were compared between 6 horses, receiving 1% voriconazole applied topically (0.2 mL, q4h) (Vori-Top) or 1.7% voriconazole-thermogel (0.3 mL) injected SCo (Vori-Gel). For the Vori-Gel group, voriconazole concentrations were measured in AH and tears at day 2 and then weekly for 23 days, and at day 2 only for the Vori-Top group. Ocular inflammation was assessed weekly (Vori-Gel) using the modified Hackett-McDonald scoring system. Ocular tissue concentrations of voriconazole following SCo 1.7% voriconazole-thermogel (0.3 mL) injections were evaluated post euthanasia in 6 additional horses at 3 different time points. Three horses received bilateral injections at 2 h (n = 3, right eye (OD)) and 48 h (n = 3, left eye (OS)) prior to euthanasia, and 3 horses were injected unilaterally (OS), 7 days prior to euthanasia. Voriconazole-thermogel was easily injected and well tolerated in all cases, with no major adverse effects. On day 2, drug concentrations in tears were higher in the Vori-Top, but not statistically different from Vori-Gel groups. For the Vori-Gel group, voriconazole was non-quantifiable in the AH at any time point. Total voriconazole concentrations in the cornea were above 0.5 μg/g (the target minimum inhibitory concentration (MIC) for Aspergillus sp.) for up to 48 h; however, concentrations were below this MIC at 7 days post treatment. Conclusions: Voriconazole-thermogel was easily and safely administered to horses, and provided 48 h of sustained release of voriconazole into the cornea. This drug delivery system warrants further clinical evaluation.

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Section: Discussionsupporting

confidence: 83%

Sustained-release voriconazole-thermogel for subconjunctival injection in horses: ocular toxicity and in-vivo studies

et al. 2020

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“…When the temperature is elevated, close to body temperature, there exist a sol to gel transition where by the polymeric fluids solidifies into a hydrogel. Incorporation of bioactive agents or drugs can be done at low temperatures in the sol state of the thermogel . The thermogel can then be injected into the body where at body temperature, a gel depot can be formed at the site where it is injected which subsequently facilitate the controlled release of the bioactive agents.…”

Section: Introductionmentioning

confidence: 99%

New Poly[(R )-3-hydroxybutyrate-co -4-hydroxybutyrate] (P3HB4HB)-Based Thermogels

Wee

Liow

Liu

et al. 2017

Macromol. Chem. Phys.

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Poly[(R)‐3‐hydroxybutyrate] (P3HB) is a potential candidate for biomaterials due to its biocompatibility and biodegradability. However, P3HB needs to have tunable hydrophobicity, modification through chemical functionalization and the right hydrolytic stability to increase their potential for water‐based biomedical applications such as using them as in situ forming gels for drug delivery. This work focuses on using a copolymer, poly[(R)‐3‐hydroxybutyrate‐co‐4‐hydroxybutyrate] (P3HB4HB) in a thermogelling multiblock system with polypropylene glycol and polyethylene glycol to study the effect of the hydrophobic P3HB4HB on gelation properties, degradation, and drug release rates with reference to P3HB. Thermogels containing P3HB4HB segments show lower critical micellization concentration values in a range from 3 × 10−4 to 1.08 × 10−3 g mL−1 and lower critical gelation concentration values ranging from 2 to 6 wt% than that of gels containing P3HB. Furthermore, gels containing P3HB4HB degrade at a slower rate than the gels containing P3HB. Drug release studies of 5 µg mL−1 of doxorubicin show that gels containing P3HB4HB exhibit sustained release although the release rates are faster than gels containing P3HB. However, this can be modified by varying the concentration of the gels used. Process optimization of purifying the starting material is one important factor before the synthesis of these biomaterials.

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“…Among various physical stimuli, temperature‐responsive supramolecular hydrogels are the most widely studied systems, where the hydrogelators undergo sol–gel or gel–sol transitions in response to subtle changes in their surrounding temperature . Akin to thermoreversible hydrogels, the temperature‐dependent phase transitions of supramolecular hydrogels are largely driven by hydrophilic and hydrophobic interactions . One of the first temperature‐responsive supramolecular hydrogels was based on glycosylated amino acid derivatives, for example, N ‐acetyl‐galactosamine‐appended amino acid (GalNAc‐aa), which self‐assembles into a hydrogel above its critical gelation concentration (CGC) ( Figure 2 A) .…”

Section: Physical Stimuli‐responsive Hydrogelsmentioning

confidence: 99%

Stimuli‐Responsive Supramolecular Hydrogels and Their Applications in Regenerative Medicine

Hoque

Sangaj

Varghese

2018

Macromolecular Bioscience

144

108

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Supramolecular hydrogels are a class of self-assembled network structures formed via non-covalent interactions of the hydrogelators. These hydrogels capable of responding to external stimuli are considered to be smart materials due to their ability to undergo sol–gel and/or gel–sol transition upon subtle changes in their surroundings. Such stimuli-responsive hydrogels are intriguing biomaterials with applications in tissue engineering, delivery of cells and drugs, modulating tissue environment to promote innate tissue repair, and imaging for medical diagnostics among others. This review summarizes the recent developments in stimuli-responsive supramolecular hydrogels and their potential applications in regenerative medicine. Specifically, various structural aspects of supramolecular hydrogelators involved in self-assembly, the role of external stimuli in tuning/controlling their phase transitions, and how these functions could be harnessed to advance applications in regenerative medicine are focused on. Finally, the key challenges and future prospects for these versatile materials are briefly described.

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Sustained intravitreal delivery of dexamethasone using an injectable and biodegradable thermogel

Cited by 87 publications

References 59 publications

Sustained-release voriconazole-thermogel for subconjunctival injection in horses: ocular toxicity and in-vivo studies

Sustained-release voriconazole-thermogel for subconjunctival injection in horses: ocular toxicity and in-vivo studies

New Poly[(R )-3-hydroxybutyrate-co -4-hydroxybutyrate] (P3HB4HB)-Based Thermogels

Stimuli‐Responsive Supramolecular Hydrogels and Their Applications in Regenerative Medicine

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