Polymer Implants for Intratumoral Drug Delivery and Cancer Therapy

Weinberg, Brent D.; Blanco, Elvin; Gao, Jinming

doi:10.1002/jps.21038

Cited by 134 publications

(86 citation statements)

References 105 publications

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“…Combining minimally-invasive treatments with controlled release technology provides opportunities for treating cancers in a safe and effective manner by placing drug-loaded implants directly into solid tumors or in resection cavities. However, it is likely that future chemotherapeutic implants will be optimized for use in a variety of different tumors to maximize patient comfort and survival [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

3D printing of PCL/Fluorouracil tablets by selective laser sintering: Properties of implantable drug delivery for cartilage cancer treatment

Gv¹,

Fe²,

Gb³

et al. 2017

Rheumatol Orthop Med

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In this study, implantable polycaprolactone/fluorouracil tablets were additively manufactured by selective laser sintering using different laser power levels. PCL/FU tablets showed on SEM-EDS small particles of fluorouracil dispersed on the surface and into the porous PCL matrix. The crystallinity values for the PCL/FU tablets were lower than for the pure PCL tablets, probably due to interaction of the FU particles with the polymer chains during the solidification process. The PCL/FU tablets prepared using the higher laser power (7 W) had the highest flexural modulus, probably due to better PCL particle coalescence, higher sinter degree and the dispersion of FU particles in the co-continuous porous PCL matrix. Initially the PCL/FU tablets provided a rapid release of a high concentration of the drug at the site of the cancer cells and a subsequent controlled release sustaining levels of the chemotherapeutic agent in the region of the tumor. This 2-stage release of the drug can be a desirable profile in cartilage cancer treatment.

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Section: Introductionmentioning

confidence: 99%

3D printing of PCL/Fluorouracil tablets by selective laser sintering: Properties of implantable drug delivery for cartilage cancer treatment

Gv¹,

Fe²,

Gb³

et al. 2017

Rheumatol Orthop Med

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“…A therapeutic implant for localized disease should have many advantages over its IV or oral equivalent: minimal systemic side effects; elimination of daily dosing and maintenance of steady state drug concentration; better patient comfort and compliance, and only local drug delivery [1] [2]. This would also have high applicability for a host of chronic diseases in addition to cancer [3].…”

Section: Introductionmentioning

confidence: 99%

A Totally Absorbable Multilayer PLGA Implant Device Containing Doxorubicin Inhibited Tumor Growth and Metastasis without Systemic Toxicity in Murine Breast Cancer and an Ideal Pharmacological Paradigm for Regional Chemotherapy

Elzey¹,

Torregrosa-Allen²,

Li³

et al. 2016

JBM

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We hypothesize that a cylinder implant made of multilayer Poly-lactic-co-glycolic-acid (PLGA) membrane can be a method for controlled and extended drug release. We fashioned a multilayer cylindrical implant termed STID100 that released doxorubicin for 3 weeks in an orthotopic 4T1 breast cancer model in Balb/C mice. This implant starts as a thin doxorubicin-embedded PLGA membrane, and is then rolled into a cylinder containing an air gap between the membrane layers. Its controlled sustained release delivered 2× the amount of the intravenous (IV) equivalent of doxorubicin, inhibited the primary tumor, and prevented lung metastasis. Importantly it did not cause weight loss, splenomegaly, or cardiac toxicity vs systemically administrated doxorubicin. This favorable safety profile is further substantiated by the finding of no detectable plasma doxorubicin in multiple time points during the 3-week period, and low tumor doxorubicin concentration. The implant system delivered to the specification of an ideal pharmacological paradigm might offer a better coverage of the local tumor, significantly preventing metastatic spread with less drug toxicity to many vital organs, compared to the traditional pharmacology of IV route. The profile of STID made it an attractive therapeutic alternative in metastatic tumor prevention, pain management * Corresponding author. B. Elzey et al. 67and many other diverse clinical scenarios.

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“…However, the drug concentration at each depth of the skin has been predicted using various mathematical equations [13][14][15][16][17][18]. We previously reported that the cutaneous disposition of topically applied drugs could be predicted using the difference method based on Fick's 2 nd law of diffusion, and also that the average drug concentration in the stratum corneum and viable epidermis/dermis could be determined separately [19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Potential of imaging analysis in establishing skin concentration-distance profiles for topically applied FITC-dextran 4 kDa

Kijima¹,

Masaki²,

Kadhum³

et al. 2015

ADMET DMPK

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Quantitatively determining the skin concentration-distance profiles of topically applied drugs is important for evaluating their safety and efficacy. The aim of the present study was to quantitatively visualize the distribution of hydrophilic drugs through the skin using confocal laser scanning microscopy (CLSM) in order to obtain skin concentration-distance profiles. FITC-dextran with a molecular weight of approximately 4 kDa (FD-4) was selected as the model fluorescent drug in the present study, and excised pig ear skin was used. The skin concentration of FD-4 at each depth of a skin section was assessed by imaging analysis of the intensity of fluorescence. The FD-4 skin concentration-distance profile obtained was analyzed usingFick's second law of diffusion, and was markedly similar to that using skin permeation parameters in the skin permeation study. These results suggest that the present CLSM method may be a promising tool for quantitatively visualizing the concentration-distance profiles of drugs through the skin.

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Polymer Implants for Intratumoral Drug Delivery and Cancer Therapy

Cited by 134 publications

References 105 publications

3D printing of PCL/Fluorouracil tablets by selective laser sintering: Properties of implantable drug delivery for cartilage cancer treatment

3D printing of PCL/Fluorouracil tablets by selective laser sintering: Properties of implantable drug delivery for cartilage cancer treatment

A Totally Absorbable Multilayer PLGA Implant Device Containing Doxorubicin Inhibited Tumor Growth and Metastasis without Systemic Toxicity in Murine Breast Cancer and an Ideal Pharmacological Paradigm for Regional Chemotherapy

Potential of imaging analysis in establishing skin concentration-distance profiles for topically applied FITC-dextran 4 kDa

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