Prevention of in vivo lung tumor growth by prolonged local delivery of hydroxycamptothecin using poly(ester-carbonate)-collagen composites

Wolinsky, Jesse B.; Liu, Rong; Walpole, Joe; Chirieac, Lucian R.; Colson, Yolonda L.; Grinstaff, Mark W.

doi:10.1016/j.jconrel.2010.02.022

Cited by 56 publications

(42 citation statements)

References 35 publications

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“…In fact, preservation of long term activity might be related to the chemical stabilization of the SN-38 lactone in the hydrophobic PLA matrix, in line with previous studies reporting that campthothecins loaded in polymers or gels were stabilized in the active lactone form [34][35][36][37]. Drugs blended in polymers are usually in molecular dispersion (amorphous) and not crystalline [38].…”

Section: Sn-38 Pharmacokinetics In the Surgical Bed Lactone Sn-38 Cosupporting

confidence: 78%

SN-38-loaded nanofiber matrices for local control of pediatric solid tumors after subtotal resection surgery

et al. 2016

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In addition to surgery, local tumor control in pediatric oncology requires new treatments as an alternative to radiotherapy. SN-38 is an anticancer drug with proved activity against several pediatric solid tumors including neuroblastoma, rhabdomyosarcoma and Ewing sarcoma. Taking advantage of the extremely low aqueous solubility of SN-38, we have developed a novel drug delivery system (DDS) consisting of matrices made of poly(lactic acid) electrospun polymer nanofibers loaded with SN-38 microcrystals for local release in difficultto-treat pediatric solid tumors. To model the clinical scenario, we conducted extensive preclinical experiments to characterize the biodistribution of the released SN-38 using microdialysis sampling in vivo. We observed that the drug achieves high concentrations in the virtual space of the surgical bed and 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 3 penetrates a maximum distance of 2 mm within the tumor bulk. Subsequently, we developed a model of subtotal tumor resection in clinically relevant pediatric patient-derived xenografts and used such models to provide evidence of the activity of the SN-38 DDS to inhibit tumor regrowth. We propose that this novel DDS could represent a potential future strategy to avoid harmful radiation therapy as a primary tumor control together with surgery.

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Section: Sn-38 Pharmacokinetics In the Surgical Bed Lactone Sn-38 Cosupporting

confidence: 78%

SN-38-loaded nanofiber matrices for local control of pediatric solid tumors after subtotal resection surgery

et al. 2016

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“…The superhydrophobic meshes under investigation are electrospun poly(ε-caprolactone) (PCL) doped with 10% poly(glycerol monostearate-co-ε-caprolactone) (PGC-C18) (Figure 2A). PGC-C18 was selected as the polymer dopant due to the relative ease in functionalizing the backbone with many pendant groups, including stearic acid [21, 27, 31], where the addition of 10% PGC-C18 produces the desired superhydrophobic effect due to a high apparent contact angle (143°) (Table 1). PCL was purchased, whereas PGC-C18 was synthesized as shown in Figure 2A.…”

Section: Resultsmentioning

confidence: 99%

3D superhydrophobic electrospun meshes as reinforcement materials for sustained local drug delivery against colorectal cancer cells

Yohe

Herrera

Colson

et al. 2012

Journal of Controlled Release

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143

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In this work we expand upon a recently reported local drug delivery device, where air is used as a degradable component of our material to control drug release (J. Am. Chem. Soc. 2012, 134, 2016-2019). We consider its potential use as a drug loaded strip to provide both mechanical stability to the anastomosis, and as a means to release drug locally over prolonged periods for prevention of locoregional recurrence in colorectal cancer. Specifically, we electrospun poly(ε-caprolactone) (PCL) with the hydrophobic polymer dopant poly(glycerol monostearate-co-ε-caprolactone) (PGC-C18) and used the resultant mesh to control the release of two anticancer drugs (CPT-11 and SN-38). The increase in mesh hydrophobicity with PGC-C18 addition slows drug release both by the traditional means of drug diffusion, as well as by increasing the stability of the entrapped air layer to delay drug release. We demonstrate that superhydrophobic meshes have mechanical properties appropriate for surgical buttressing of the anastomosis, permit non-invasive assessment of mesh location and documentation of drug release via ultrasound, and release chemotherapy over a prolonged period of time (>90 days) resulting in significant tumor cytotoxicity against a human colorectal cell line (HT-29).

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“…Repeated exposure of the 10HCPTloaded or paclitaxel-loaded polymer films to fresh lung cancer cells in vitro afforded cell death for over 50 days. 201,202 The paclitaxel-loaded poly(glycerol monostearate- co -caprolactone) films prevented locoregional recurrence of tumor in vivo. 201 The overall freedom from locoregional recurrence is 83% with the use of the paclitaxel-loaded films, while the freedom from recurrence in mice treated with unloaded films or paclitaxel administered intraperitoneally or locally at the surgical site is significantly lower at 12, 22, and 0%, respectively.…”

Section: Glycerol Synthonsmentioning

confidence: 99%

Synthetic Biomaterials from Metabolically Derived Synthons

et al. 2016

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The utility of metabolic synthons as the building blocks for new biomaterials is based on the early application and success of hydroxy acid based polyesters as degradable sutures and controlled drug delivery matrices. The sheer number of potential monomers derived from the metabolome (e.g., lactic acid, dihydroxyacetone, glycerol, fumarate) gives rise to almost limitless biomaterial structural possibilities, functionality, and performance characteristics, as well as opportunities for the synthesis of new polymers. This review describes recent advances in new chemistries, as well as the inventive use of traditional chemistries, toward the design and synthesis of new polymers. Specific polymeric biomaterials can be prepared for use in varied medical applications (e.g., drug delivery, tissue engineering, wound repair, etc.) through judicious selection of the monomer and backbone linkage.

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Prevention of in vivo lung tumor growth by prolonged local delivery of hydroxycamptothecin using poly(ester-carbonate)-collagen composites

Cited by 56 publications

References 35 publications

SN-38-loaded nanofiber matrices for local control of pediatric solid tumors after subtotal resection surgery

SN-38-loaded nanofiber matrices for local control of pediatric solid tumors after subtotal resection surgery

3D superhydrophobic electrospun meshes as reinforcement materials for sustained local drug delivery against colorectal cancer cells

Synthetic Biomaterials from Metabolically Derived Synthons

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