Sustained-release hydrogels of topotecan for retinoblastoma

Taich, Paula Juliana; Morettón, Marcela A.; Solé, María; Winter, Ursula; Bernabeu, Ezequiel; Croxatto, J. Oscar; Oppezzo, Javier; Williams, Gustavo; Chantada, Guillermo; Schaiquevich, Paula

doi:10.1016/j.colsurfb.2016.07.001

Cited by 20 publications

(8 citation statements)

References 25 publications

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“…In addition, poloxamer can be biodegraded without posing a potential risk to the health of the patient (eg, polymer residue in the organs of the patient). Interestingly, Taich et al (2016) prepared a sustained-release hydrogel of topotecan using another material, namely poly(ε-caprolactone)-poly(ethyleneglycol)-poly(ε-caprolactone) 50. Majumder et al (2018) designed a multicompartment hydrogel that can facilitate the time-resolved delivery feature of combination therapy on glioblastoma.…”

Section: Discussionmentioning

confidence: 99%

<p>A temperature-sensitive phase-change hydrogel of topotecan achieves a long-term sustained antitumor effect on retinoblastoma cells</p>

Huo¹,

Wang²,

Liu³

et al. 2019

OTT

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Background Retinoblastoma (Rb) is one of the most common malignancies among children. Following early diagnosis and prompt treatment, the clinical outcome or prognosis of Rb is promising. However, the prognosis or survival rates of patients with late-stage Rb remain poor. Current therapeutic strategies for advanced Rb mainly involve the use of advanced chemotherapeutic options. However, the efficacy of these strategies is not satisfactory. Therefore, the development of novel strategies to achieve a more effective antitumor effect on late-stage Rb is of crucial importance. Methods and materials Topotecan was dissolved in phosphate-buffered saline and prepared into a temperature-sensitive phase-change hydrogel (termed Topo-Gel). Moreover, Topo-Gel was injected into tumor tissues formed by Y79 cells (an Rb cell line) in nude mice to examine the long-term release and long-acting antitumor effect of Topo-Gel on Rb tumors. Results Topo-Gel transforms from liquid to a hydrogel at near body temperatures (phase-change temperature [T 1/2 ] was 37.23±0.473 °C), and maintains the slow release of topotecan in Rb tumor tissues. Following the subcutaneous injection of Topo-Gel, the treatment induced long-acting inhibition of tumor growth and relieved the adverse effects associated with topotecan. Topo-Gel, a temperature-sensitive phase-change hydrogel, is a slow-release system that prolongs the presence of topotecan in Rb tissues, and preserves the efficacy of topotecan in the long term. Conclusion Preparation of topotecan into a temperature-sensitive phase-change hydrogel achieves a long-term sustained antitumor effect on Rb cells, and may be a useful strategy for the treatment of intraocular Rb.

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Section: Discussionmentioning

confidence: 99%

<p>A temperature-sensitive phase-change hydrogel of topotecan achieves a long-term sustained antitumor effect on retinoblastoma cells</p>

Huo¹,

Wang²,

Liu³

et al. 2019

OTT

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“…Furthermore, amphiphilic macromolecules can act as a solubilizer for hydrophobic and insoluble drugs, significantly increasing their water solubility [ 15 ]. To date, a considerable amount of thermosensitive hydrogels based on PCL/poly(ethylene oxide) (PEG) [ 16 , 17 , 18 , 19 , 20 ], PLA/PEG [ 21 , 22 ], PCL/PLA/PEG [ 3 , 23 , 24 ], and PCL/PGA/PEG [ 25 , 26 ] block copolymers have been described in the literature as potential DDSs with attractive properties.…”

Section: Introductionmentioning

confidence: 99%

Dual-Stimuli-Sensitive Smart Hydrogels Containing Magnetic Nanoparticles as Antitumor Local Drug Delivery Systems—Synthesis and Characterization

Kasiński

Świerczek

Zielińska–Pisklak

et al. 2023

IJMS

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The aim of this study was to develop an innovative, dual-stimuli-responsive smart hydrogel local drug delivery system (LDDS), potentially useful as an injectable simultaneous chemotherapy and magnetic hyperthermia (MHT) antitumor treatment device. The hydrogels were based on a biocompatible and biodegradable poly(ε-caprolactone-co-rac-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-rac-lactide) (PCLA-PEG-PCLA, PCLA) triblock copolymer, synthesized via ring-opening polymerization (ROP) in the presence of a zirconium(IV) acetylacetonate (Zr(acac)4) catalyst. The PCLA copolymers were successfully synthesized and characterized using NMR and GPC techniques. Furthermore, the gel-forming and rheological properties of the resulting hydrogels were thoroughly investigated, and the optimal synthesis conditions were determined. The coprecipitation method was applied to create magnetic iron oxide nanoparticles (MIONs) with a low diameter and a narrow size distribution. The magnetic properties of the MIONs were close to superparamagnetic upon TEM, DLS, and VSM analysis. The particle suspension placed in an alternating magnetic field (AMF) of the appropriate parameters showed a rapid increase in temperature to the values desired for hyperthermia. The MIONs/hydrogel matrices were evaluated for paclitaxel (PTX) release in vitro. The release was prolonged and well controlled, displaying close to zero-order kinetics; the drug release mechanism was found to be anomalous. Furthermore, it was found that the simulated hyperthermia conditions had no effect on the release kinetics. As a result, the synthesized smart hydrogels were discovered to be a promising antitumor LDDS, allowing simultaneous chemotherapy and hyperthermia treatment.

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“…Compared to melphalan, TPT has a longer intra-ocular half-life [ 10 ], and it has been reported that intravitreal monotherapy with TPT shows retinal non-toxicity in a rabbit model [ 11 ], even in high doses (up to 50 µg administered weekly) [ 12 ]. Recently, the successful control of vitreous disease was achieved with intravitreal TPT applied as a drug solution [ 13 , 14 , 15 ] or using injectable TPT delivery systems such as hydrogels [ 16 , 17 ] or nanoparticles [ 18 ]. Despite these achievements, intravitreal therapy cannot be used in all patients with seeding, and it is even contraindicated in case of uveal or anterior chamber involvement [ 9 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Cryotherapy in Vitreous Concentrations of Topotecan Delivered by Episcleral Hydrogel Implant

et al. 2022

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Transscleral diffusion delivery of chemotherapy is a promising way to reach the vitreal seeds of retinoblastoma, the most common intraocular malignancy in childhood. In this in vivo study, the delivery of topotecan via lens-shaped, bi-layered hydrogel implants was combined with transconjunctival cryotherapy to assess whether cryotherapy leads to higher concentrations of topotecan in the vitreous. The study included 18 New Zealand albino rabbits; nine rabbits received a topotecan-loaded implant episclerally and another nine rabbits received transconjunctival cryotherapy superotemporally 2 weeks before implant administration. Median vitreous total topotecan exposures (area under the curve, AUC) were 455 ng·h/mL for the cryotherapy group and 281 ng·h/mL for the non-cryotherapy group, and were significantly higher in the cryotherapy group, similar to maximum levels. Median plasma AUC were 50 ng·h/mL and 34 ng·h/mL for the cryotherapy and non-cryotherapy groups, respectively, with no statistically significant differences between them. In both groups, AUC values in the vitreous were significantly higher than in plasma, with plasma exposure at only approximately 11–12% of the level of vitreous exposure. The results confirmed the important role of the choroidal vessels in the pharmacokinetics of topotecan during transscleral administration and showed a positive effect of cryotherapy on intravitreal penetration, resulting in a significantly higher total exposure in the vitreous.

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Sustained-release hydrogels of topotecan for retinoblastoma

Cited by 20 publications

References 25 publications

<p>A temperature-sensitive phase-change hydrogel of topotecan achieves a long-term sustained antitumor effect on retinoblastoma cells</p>

<p>A temperature-sensitive phase-change hydrogel of topotecan achieves a long-term sustained antitumor effect on retinoblastoma cells</p>

Dual-Stimuli-Sensitive Smart Hydrogels Containing Magnetic Nanoparticles as Antitumor Local Drug Delivery Systems—Synthesis and Characterization

The Role of Cryotherapy in Vitreous Concentrations of Topotecan Delivered by Episcleral Hydrogel Implant

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