Proof-of-Concept of Polymeric Sol-Gels in Multi-Drug Delivery and Intraoperative Image-Guided Surgery for Peritoneal Ovarian Cancer

McKenzie, Matthew; Betts, David R.; Suh, Amy; Bui, Kathryn; Tang, Rui; Liang, Kexian; Achilefu, Samuel; Kwon, Glen S.; Cho, Hyunah

doi:10.1007/s11095-016-1968-3

Cited by 18 publications

(9 citation statements)

References 18 publications

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“…Biodegradable hydrogels are typically soft materials and have been used in multiple biomedical applications, [1][2][3][4] such as tissue engineering scaffolds and drug delivery carriers. They can include biodegradable components such as poly(lactic acid) (PLA), 5 poly(e-caprolactone) (PCL), 6 poly(D,L-lactide-co-glycolide) (PLGA), 7 and poly(e-caprolactone-co-lactide) (PCLA) 8 as hydrophobic blocks copolymerized with hydrophilic components such as poly(ethylene glycol) (PEG). Among the various classes of hydrogels developed, the copolymers of poly(L-lactide)-copolyethyleneglycol-co-poly(L-lactide) (PLLA-PEG-PLLA) and their derivatives show promising potential in a number of biomedical applications, for example, with materials designed to form stable self-assembling micellar structures 9 with the hydrophobic core allowing good loading of hydrophobic drugs, while also undergoing biodegradation.…”

Section: Introductionmentioning

confidence: 99%

Biodegradable pH-responsive hydrogels for controlled dual-drug release

Qiu

Yang

et al. 2018

J. Mater. Chem. B

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Section: Introductionmentioning

confidence: 99%

Biodegradable pH-responsive hydrogels for controlled dual-drug release

Qiu

Yang

et al. 2018

J. Mater. Chem. B

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“…150 mg/mL exists as a flower-like polymeric micelle with a z-average diameter at ca. 140 nm, a shell of PEG loops, and a core of PLGA that presumably is the location of the solubilized drug(s) [16]. As g-E, the water solubility of EpoB increased 15-fold from 25 μg/mL to 0.371 mg/mL at 93% loading efficiency (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Pre-clinical evaluation of a themosensitive gel containing epothilone B and mTOR/Hsp90 targeted agents in an ovarian tumor model

Shin

Kwon

2017

Journal of Controlled Release

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Despite clinical remission of epithelial ovarian cancer (EOC) after surgical resection and first-line chemotherapy, about 60% of patients will re-develop peritoneal metastasis and about 50% will relapse with chemoresistant disease. Clinical studies suggest that intra-peritoneal (i.p.) chemotherapy effectively treats residual EOC after cyto-reduction by gaining direct access into the peritoneal cavity, enabling elevated drug levels versus intravenous (i.v.) injection. However, chemoresistant disease is still problematic. To overcome resistance against microtubule stabilizing agents such as taxanes, epothilone B (EpoB) has merit, especially in combination with molecular targeted agents that inhibit heat shock protein 90 (Hsp90) and/or mammalian target of rapamycin (mTOR). In this paper, we report on the successful loading and solubilization of EpoB in a poly(d,l-lactic-co-glycolic acid)-block-poly(ethylene glycol)-block-poly(d,l-lactic-co-glycolic acid) (PLGA-b-PEG-b-PLGA) thermosensitive gel (g-E). Further, we report on successful co-loading of 17-AAG (Hsp90) and rapamycin (mTOR) (g-EAR). After i.p. injection in mice, g-EAR showed gelation in the peritoneum and sustained, local-regional release of EpoB, 17-AAG, and rapamycin. In a luciferase-expressing ES-2 (ES-2-luc) ovarian cancer xenograft model, single i.p. injections of g-E and g-EAR delayed bioluminescence from metastasizing ES-2-luc cells for 2 and 3weeks, respectively, despite fast drug release for g-EAR in vivo versus in vitro. In summary, a PLGA-b-PEG-b-PLGA sol-gel has loading and release capacities for EpoB and its combinations with 17-AAG and rapamycin, enabling a platform for i.p. delivery, sustained multi-drug exposure, and potent antitumor efficacy in an ES-2-luc, ovarian cancer i.p. xenograft model.

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“…Due to this unique structure consisting of micelles (hydrophobic core-hydrophilic exterior), nanogels are capable of incorporating hydrophilic compounds into the exterior of the micellar networks and hydrophobic compounds into the core of the micelles ( Figure 1 ) [ 3 ]. Poly (D,L-lactide-co-glycolide)- block -poly(ethylene glycol)- block -poly(D,L-lactide-co-glycolide)(PLGA- b -PEG- b -PLGA; BAB block copolymer) nanogels ( Figure 1 a) have been widely used to locally deliver hydrophobic drugs at a slow elution rate [ 9 , 10 ]. Cho et al successfully prepared a thermosensitive PLGA- b -PEG- b -PLGA nanogels which entrain three poorly water-soluble compounds, paclitaxel (a mitotic inhibitor), rapamycin (an mTOR inhibitor), and LS301 (cysteine-glycine-arginine-aspartic acid-serine-proline-cysteine-lysine-cypate, a cypate-based angiogenesis-targeting fluorescence imaging agent).…”

Section: Nanogels For Delivery Of Poorly Water Soluble Drugsmentioning

confidence: 99%

Nanogels for Pharmaceutical and Biomedical Applications and Their Fabrication Using 3D Printing Technologies

2018

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Nanogels are hydrogels formed by connecting nanoscopic micelles dispersed in an aqueous medium, which give an opportunity for incorporating hydrophilic payloads to the exterior of the micellar networks and hydrophobic payloads in the core of the micelles. Biomedical and pharmaceutical applications of nanogels have been explored for tissue regeneration, wound healing, surgical device, implantation, and peroral, rectal, vaginal, ocular, and transdermal drug delivery. Although it is still in the early stages of development, due to the increasing demands of precise nanogel production to be utilized for personalized medicine, biomedical applications, and specialized drug delivery, 3D printing has been explored in the past few years and is believed to be one of the most precise, efficient, inexpensive, customizable, and convenient manufacturing techniques for nanogel production.

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Proof-of-Concept of Polymeric Sol-Gels in Multi-Drug Delivery and Intraoperative Image-Guided Surgery for Peritoneal Ovarian Cancer

Abstract: TheranoGel prepared via a facile lyophiliation method enabled successful IP delivery of multi-drugs and exhibited excellent theranostic activity in vivo.

Cited by 18 publications

References 18 publications

Biodegradable pH-responsive hydrogels for controlled dual-drug release

Biodegradable pH-responsive hydrogels for controlled dual-drug release

Pre-clinical evaluation of a themosensitive gel containing epothilone B and mTOR/Hsp90 targeted agents in an ovarian tumor model

Nanogels for Pharmaceutical and Biomedical Applications and Their Fabrication Using 3D Printing Technologies

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