The use of submicron/nanoscale PLGA implants to deliver paclitaxel with enhanced pharmacokinetics and therapeutic efficacy in intracranial glioblastoma in mice

Ranganath, Sudhir H.; Fu, Yilong; Arifin, Davis Yohanes; Kee, Irene; Zheng, Lin; Lee, How-Sung; Chow, Pierce K. H.; Wang, Chi-Hwa

doi:10.1016/j.biomaterials.2010.03.002

Cited by 103 publications

(65 citation statements)

References 29 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]. Our work shows for the first time that microcrystals of a poorly water-soluble hydrolysable drug such as SN-38 could be stabilized by incorporation into the nanofiber mesh.…”

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

confidence: 56%

“…Other authors have used terminal sampling methods to propose that localized drug delivery might achieve such therapeutic penetration to ratios greater than 2 mm [38]. However, we suggest that the terminal sampling methods (after animal death) might have overestimated the drug penetration distance due to maintained drug release from the DDS into the tissue until sample collection.…”

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

confidence: 39%

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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: 56%

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

confidence: 39%

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

et al. 2016

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“…This adjuvant is associated with severe side effects, including hypersensitivity reactions, nephrotoxicity and cardiotoxicity. Alternative paclitaxel formulations have been suggested to eliminate the Cremophor EL-based vehicle and to improve the therapeutic efficacy of the drug [1][2][3][4][5][6][7] . Despite the existence of many pharmaceuticals, natural or synthetic, used in the treatment of cancer, the biological features inherent to each type of tumor, along with resistance to the chemotherapeutic agents that tumor cells can develop boost the search for new products with antineoplastic action 1,8 .…”

Section: Introductionmentioning

confidence: 99%

“…Amongst the different classes of biodegradable polymers, the thermoplastic aliphatic poly(esters) like poly(lactide) (PLA), poly(glycolide) (PGA), a have generated immense interest due to their favorable properties such as good biocompatibility, biodegradability, and mechanical strength. Also, they are easy to formulate into different devices for loading of paclitaxel [3][4][5][6][7] . Polymeric microspheres are small spherical particles, with diameters in the micrometer range (typically 1 µm to 250 µm) and are typically used in biomedical applications.…”

Section: Introductionmentioning

confidence: 99%

Preparation and characterization of paclitaxel-loaded PLDLA microspheres

Martins

Messias

Leite³

et al. 2014

Mat. Res.

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Paclitaxel (Taxol®), is a drug used to treat ovarian, breast, lung and bladder cancer. However, the low solubility of this drug in water is a major limitation in its clinical use. One strategy to overcome this limitation would be to encapsulate paclitaxel in polymeric microspheres that are biocompatible and can be used as drug carriers. The aim of this study was to use the bioresorbable, biocompatible copolymer poly-L-co-D,L-lactic acid (PLDLA) in the 70:30 rate to produce and characterize microspheres containing paclitaxel. The simple emulsion technique was used to obtain spherical microspheres that were studied by scanning electron microscopy (SEM) and atomic force microscopy (AFM). The average size of PLDLA microspheres without and with paclitaxel was 10.3 ± 1.7 µm and 12.7 ± 1.3 µm, respectively, as determined by laser light scattering (LLS). Differential scanning calorimetry (DSC) showed that pure paclitaxel had an endothermic peak corresponding to a melting point of 220 °C, which indicated its crystalline nature. The same peak was observed in a physical mixture of PLDLA + paclitaxel in which both components were present in the same proportions used to prepare the microspheres . In contrast, this peak was not observed for the drug, indicating that paclitaxel did not crystallize in PLDLA microspheres. Differential scanning calorimetry (DSC) indicated that paclitaxel was homogeneously dispersed in the PLDLA microspheres, the incorporation of paclitaxel into the microspheres did not alter the thermal properties of PLDLA. The Fourier transform infrared spectroscopy (FTIR) analysis seems to indicate the absence of chemical interaction between polymer and drugs in microspheres and the presence of drugs as a molecular dispersion in the polymer matrix. The efficiency of paclitaxel encapsulation in PLDLA microspheres was 98.0 ± 0.3%, as assessed by high performance liquid chromatography (HPLC). A kinetic study of drug release in vitro using HPLC showed an initial burst release followed by a slower release characteristic of large diameter distribution systems. PLDLA microspheres released 90 ± 4% of the drug over a 30-day period. These findings indicate that PLDLA microspheres are promising carriers for paclitaxel, with a potential for future applications in drug delivery systems.

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“…Placebo wafers have been shown to small improvements in median survivability of patients diagnosed with high-grade malignant gliomas from 11.6 to 13.9 months, and from 4.6 to 6.4 months for recurrent cases. In response, Ranganath et al have explored the controlled release of alternative chemotherapeutic agents (paclitaxel) and fadiosensitization (etanidazole) for treatment (Ranganath 2010). Since the advantages for comprehensive cancer treatment has been recognized, it is thus highly significant to develop composite polymeric surgical implant to achieve multimodality approach for fighting cancers.…”

Section: Drug Loaded Magnetic Nanocomposite Biodegradable Implants Fomentioning

confidence: 99%

Magnetic Nanocomposite Devices for Cancer Thermochemotherapy

Zhao¹,

Wang²,

Yang³

et al. 2011

Advances in Nanocomposites - Synthesis, Characterization and Industrial Applications

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The use of submicron/nanoscale PLGA implants to deliver paclitaxel with enhanced pharmacokinetics and therapeutic efficacy in intracranial glioblastoma in mice

Cited by 103 publications

References 29 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

Preparation and characterization of paclitaxel-loaded PLDLA microspheres

Magnetic Nanocomposite Devices for Cancer Thermochemotherapy

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