Clinical Considerations of Focal Drug Delivery in Cancer Treatment

Harris, Jonathan M.; Klonoski, Samuel C.; Chiu, Bill

doi:10.2174/1567201814666170224143706

Cited by 12 publications

(13 citation statements)

References 66 publications

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“…All mouse procedures were performed in accordance with the National Institute of Health protocols on Humane Care and Use of Laboratory Animals and approved by the Institutional Animal Care and Use Committee at University of Illinois at Chicago. Seven‐week old female NCr nude mice (Harlan) were used to create an orthotopic neuroblastoma tumor model as previously described . In brief, the mice were anesthetized with inhaled isoflurane and an incision was made on the left flank to locate the adrenal gland.…”

Section: Methodsmentioning

confidence: 99%

“…Local drug delivery is emerging as an alternative to the traditional systemic delivery of therapeutics for the management of solid tumors . Local administration of therapeutic agents can offer significant benefits to patients, including reducing the frequency and severity of toxic side effects associated with systemic therapies . Clinically, local chemotherapy delivery systems, such as the Gliadel ® Wafer, have been employed for the treatment of solid tumors .…”

Section: Introductionmentioning

confidence: 99%

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Local delivery of dinutuximab from lyophilized silk fibroin foams for treatment of an orthotopic neuroblastoma model

et al. 2020

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Immunotherapy targeting GD2 is a primary treatment for patients with high-risk neuroblastoma. Dinutuximab is a monoclonal antibody with great clinical promise but is limited by side effects such as severe pain. Local delivery has emerged as a potential mechanism to deliver higher doses of therapeutics into the tumor bed, while limiting systemic toxicity. We aim to deliver dinutuximab locally in a lyophilized silk fibroin foam for the treatment of an orthotopic neuroblastoma mouse model. Dinutuximabloaded silk fibroin foams were fabricated through lyophilization. In vitro release profile and bioactivity of the release through complement-dependent cytotoxicity were characterized. MYCN-amplified neuroblastoma cells (KELLY) were injected into the left gland of mice to generate an orthotopic neuroblastoma model. Once the tumor volume reached 100 mm 3 , dinutuximab-, human IgG-, or buffer-loaded foams were implanted into the tumor and growth was monitored using high-resolution ultrasound. Post-resection histology was performed on tumors. Dinutuximab-loaded silk fibroin foams exhibited a burst release, with slow release thereafter in vitro with maintenance of bioactivity. The dinutuximab-loaded foam significantly inhibited xenograft tumor growth compared to IgG-and buffer-loaded foams. Histological analysis revealed the presence of dinutuximab within the tumor and neutrophils and macrophages infiltrating into dinutuximab-loaded silk foam. Tumors treated with local dinutuximab had decreased MYCN expression on histology compared to control or IgG-treated tumors. Silk fibroin foams offer a mechanism for local release of dinutuximab within the neuroblastoma tumor. This local delivery achieved a significant decrease in tumor growth rate in a mouse orthotopic tumor model. K E Y W O R D SCh14.18, dinutuximab, immunotherapy, local delivery, neuroblastoma, silk fibroin

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Local delivery of dinutuximab from lyophilized silk fibroin foams for treatment of an orthotopic neuroblastoma model

et al. 2020

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“…Alternatively, focal (i.e. local) cancer therapy is used clinically for cancer therapy (reviewed in [33,34]). Examples include intravesical therapy for bladder cancer, hepatic arterial infusion therapy for hepatocellular carcinoma, brachytherapy of early stage breast cancer and delivery of carmustine by controlled-release polymeric wafers (Gliadel wafers) for the post-resection treatment of high-grade malignant glioma and recurrent glioblastoma multiforme.…”

Section: Delivery Of Therapeutic Payloads -Key Considerationsmentioning

confidence: 99%

“…Examples include intravesical therapy for bladder cancer, hepatic arterial infusion therapy for hepatocellular carcinoma, brachytherapy of early stage breast cancer and delivery of carmustine by controlled-release polymeric wafers (Gliadel wafers) for the post-resection treatment of high-grade malignant glioma and recurrent glioblastoma multiforme. Anticancer drug delivery systems based on silk films [35][36][37], foams [38] and self-assembling silk hydrogels [38,39] are currently showing encouraging results in preclinical animal models of breast cancer and neuroblastoma [33].…”

Section: Delivery Of Therapeutic Payloads -Key Considerationsmentioning

confidence: 99%

Reverse-engineered Silk Hydrogels for Cell and Drug Delivery

Seib

2018

Ther. Deliv.

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Silk is an important biopolymer for (bio)medical applications because of its unique and highly versatile structure and its robust clinical track record in human medicine. Silk can be processed into many material formats, including physically and chemically crosslinked hydrogels that have almost limitless applications ranging from tissue engineering to biomedical imaging and sensing. This concise review provides a detailed background of silk hydrogels, including silk structure-function relationships, biocompatibility and biodegradation, and it explores recent developments in silk hydrogel utilization, with specific reference to drug and cell delivery. We address common pitfalls and misconceptions while identifying emerging opportunities, including 3D printing.

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“…The delivery of chemotherapy through an intravenous route has been the mainstay of neuroblastoma treatment, and toxicity from the systemic chemotherapy has resulted in significant patient morbidity such as cardiotoxicity, myelosuppression, renal toxicity, and adverse long term problems including secondary malignancy [2]. As novel drug reservoir systems become available, the adoption of improved drug delivery methods that can maximize tumor kill and minimize systemic side effects is a top-priority, especially for the pediatric population [3–5]. Previously, we have utilized sustained release silk platforms to treat orthotopic neuroblastoma mouse xenografts by implanting the platform into the center of the tumor [6].…”

Section: Introductionmentioning

confidence: 99%

Manipulation of variables in local controlled release vincristine treatment in neuroblastoma

Coburn

Harris

Cunningham

et al. 2017

Journal of Pediatric Surgery

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Introduction Local drug delivery minimizes systemic toxicity while delivering high-dose chemotherapy for neuroblastoma patients. We hypothesized that varying burst and maintenance dosing of implanted silk platforms would improve survival. Methods Platforms were loaded with vincristine 25µg, 50µg, 100µg, 200µg varying burst (released 1–4 days post-implantation) and maintenance (over next 20 days) dosing. Orthotopic tumors were created in mice using human neuroblastoma KELLY cells. Silk platforms were implanted into tumors when volume>300mm3. Tumor volume was monitored weekly with ultrasound. Experimental endpoints were tumor volume>1000mm3 or weight loss>25%. Results Drug release ranged from burst dosing 18.2–80.9µg, maintenance 5.0–111.6µg, and cumulative 23.3–177.4µg. Animals treated with 200µg platform died 9–13 days post-implantation, corresponding to 128.1–141.2µg released (toxic dose). Animals received 30.2±3.4µg day-one survived longer than those that received 10.1±1.1µg(p=0.03), suggesting <10.1µg day-one was insufficient. Tumors treated with 100µg or 50µg silk platform took longer to reach 1000mm3 compared to those treated with control, 44.8±9.5 days(p<0.001) and 26.7±6.7 days(p<0.05), respectively, versus 7.0±1.7 days. Overall survival correlated with higher burst(r=0.446, p=0.004) and maintenance dosing(r=0.353, p=0.02), Animal survival days=30.314+0.626×(dose on day-one)−0.020×(tumor volume at day-ten)(p <0.05). Conclusion Platform formulations can be manipulated to vary burst and maintenance dosing, summarized by an equation consisting of these variables.

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Clinical Considerations of Focal Drug Delivery in Cancer Treatment

Abstract: This review focuses the current state of local drug delivery in the treatment of solid tumors in both the pre-clinical as well as clinical investigation settings. Local drug delivery therapy offers an exciting new treatment modality for solid malignancies.

Cited by 12 publications

References 66 publications

Local delivery of dinutuximab from lyophilized silk fibroin foams for treatment of an orthotopic neuroblastoma model

Local delivery of dinutuximab from lyophilized silk fibroin foams for treatment of an orthotopic neuroblastoma model

Reverse-engineered Silk Hydrogels for Cell and Drug Delivery

Manipulation of variables in local controlled release vincristine treatment in neuroblastoma

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