Prevention of Local Tumor Recurrence Following Surgery Using Low-Dose Chemotherapeutic Polymer Films

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

doi:10.1245/s10434-009-0856-z

Cited by 61 publications

(50 citation statements)

References 38 publications

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“…Over the last decade, emerging thermosensitive hydrogels have been reported as sustainable DDSs; however, hydrogels have a relatively fast degradation speed. Polymeric films have effectively prevented cancer relapse in the resection site of primary cancers (Liu et al, 2010(Liu et al, , 2012. In agreement with the polymer films, the PDLLA nanofibers used in our study exhibited outstanding biocompatibility and biodegradability, as well as a consistent drug-release rate.…”

Section: Discussionsupporting

confidence: 79%

Preparation and therapeutic application of docetaxel-loaded poly(d,l-lactide) nanofibers in preventing breast cancer recurrence

Ding

Yang

et al. 2015

Drug Delivery

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The aim of this study was to develop docetaxel (DTX)-loaded poly-d,l-lactide (PDLLA) nanofibers and evaluate their therapeutic effect in preventing local breast cancer recurrence. DTX was incorporated into biodegradable PDLLA nanofibers by electrospinning. The surface morphology of the DTX/PDLLA nanofibers was characterized using scanning electron microscopy and wide angle X-ray diffraction. The in vitro release behavior of DTX from the fiber mats was also studied in detail. The cytotoxicity of DTX/PDLLA nanofibers was evaluated by MTT assay in 4T1 breast cancer cells. Flow cytometry revealed that DTX/PDLLA nanofibers exhibited apoptotic activity in 4T1 cells. In vivo antitumor efficacy of DTX/PDLLA nanofibers was evaluated in BALB/c mice bearing local breast tumors. Locoregional recurrence after primary tumor resection decreased obviously in mice treated with subcutaneously (16.7%) administered DTX-loaded PDLLA nanofibers, compared with the blank PDLLA nanofibers (88.9%), systemic (75.0%) or locally (77.8%) administered DTX and the control group (100%) (p < 0.05). Finally, after subcutaneous transplantation in mice, the DTX/PDLLA scaffolds presented excellent biocompatibility, as exhibited by the minimal presence of inflammatory cells in the region surrounding the scaffolds. Our results suggest that DTX/PDLLA nanofibers could have great potential for clinical application requiring local chemotherapy.

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Section: Discussionsupporting

confidence: 79%

Preparation and therapeutic application of docetaxel-loaded poly(d,l-lactide) nanofibers in preventing breast cancer recurrence

Ding

Yang

et al. 2015

Drug Delivery

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“…21,22 Therefore, since 1970s fundamental explorations on effective drug delivery systems have aimed to optimize the anti-tumor activity of parent drugs/radioactive particles, diminish non-selective toxicity and improve quality of life for cancer patients. 8,23,24 Several novel DDSs including expansile nanoparticles, 25 polymeric platforms 11,26 and chitosan hydrogel, 27,28 have been applied to retard or postpone tumor relapse in animal models. Despite plenty of advantages in local therapy, some of the referring DDSs have confronted certain barriers to maintain sustained local drug concentration in satisfactory ways.…”

Section: Discussionmentioning

confidence: 99%

“…However some vehicles have manifested positive effects to the incision wound. 11 Despite specially designed wound dressings made from biomaterials, such as collagen, hyaluronic acid, chitosan, alginates and elastin, few reports about impact of local DDSs on wound healing were noted. [12][13][14] We previously synthesized a series of thermosensitive hydrogels based on biocompatible poly(ethyleneglycol)-poly(3-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) copolymers.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic application of injectable thermosensitive hydrogel in preventing local breast cancer recurrence and improving incision wound healing in a mouse model

et al. 2012

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Many drug delivery systems (DDSs) have been investigated for local targeting of malignant disease with the intention of increasing anti-tumor activity and minimizing systemic toxicity. An injectable thermosensitive hydrogel was applied to prevent locoregional recurrence of 4T1 breast cancer in a mouse model. The presented hydrogel, which is based on poly(ethyleneglycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE), flows freely at normal temperature, forms a gel within seconds in situ at body temperature, and eventually releases the drug in a consistent and sustained fashion as it gradually biodegrades. Locoregional recurrence after primary tumor removal was significantly inhibited in mice treated with the paclitaxel (PTX)-loaded PECE hydrogel subcutaneously (9.1%) administered, compared with the blank hydrogel (80.0%), systemic (77.8%) and locally (75.0%) administered PTX, and the control group (100%) (P < 0.01). In addition, tensile strength measurements of the surgical incisions showed that the PECE hydrogel accelerates wound healing at postoperative day 7 (P < 0.05), and days 4 and 14 (P > 0.05), in agreement with histopathological examinations. This novel DDSs represents a promising approach for local adjuvant therapy in malignant disease.

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“…Further study of similar treatment modalities may have a future role in the loco-regional treatment of lung cancers. An interesting evolution of the classic implant systems loaded with anticancer drugs are for example polymer films (Liu et al, 2010) and composite materials obtained by electrospinning (Yohe et al, 2012a,b). These delivery platforms may have significant application in future lung cancer therapies, particularly in combination with nanopharmaceuticals.…”

Section: Other Approaches For Local Delivery Of Anticancer Drugsmentioning

confidence: 99%

Loco-regional administration of nanomedicines for the treatment of lung cancer

et al. 2015

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Lung cancer poses one of the most significant challenges to modern medicine, killing thousands every year. Current therapy involves surgical resection supplemented with chemotherapy and radiotherapy due to high rates of relapse. Shortcomings of currently available chemotherapy protocols include unacceptably high levels of systemic toxicity and low accumulation of drug at the tumor site. Loco-regional delivery of nanocarriers loaded with anticancer agents has the potential to significantly increase efficacy, while minimizing systemic toxicity to anticancer agents. Local drug administration at the tumor site using nanoparticulate drug delivery systems can reduce systemic toxicities observed with intravenously administered anticancer drugs. In addition, this approach presents an opportunity for sustained delivery of anticancer drug over an extended period of time. Herein, the progress in the development of locally administered nanomedicines for the treatment of lung cancer is reviewed. Administration by inhalation, intratumoral injection and means of direct in situ application are discussed, the benefits and drawbacks of each modality are explored.

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Prevention of Local Tumor Recurrence Following Surgery Using Low-Dose Chemotherapeutic Polymer Films

Abstract: Local application of paclitaxel-loaded polymer films following surgical resection can prevent local tumor recurrence without impairing wound healing.

Cited by 61 publications

References 38 publications

Preparation and therapeutic application of docetaxel-loaded poly(d,l-lactide) nanofibers in preventing breast cancer recurrence

Preparation and therapeutic application of docetaxel-loaded poly(d,l-lactide) nanofibers in preventing breast cancer recurrence

Therapeutic application of injectable thermosensitive hydrogel in preventing local breast cancer recurrence and improving incision wound healing in a mouse model

Loco-regional administration of nanomedicines for the treatment of lung cancer

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