In vivo performance of implantable biodegradable preparations delivering Paclitaxel and Etanidazole for the treatment of glioma

Naraharisetti, Pavan Kumar; Ong, Benjamin Y.S.; Xie, Jing; Lee, Timothy Kam Yiu; Wang, Chi Hwa; Sahinidis, Nikolaos V.

doi:10.1016/j.biomaterials.2006.09.044

Cited by 47 publications

(28 citation statements)

References 18 publications

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“…As a preliminary test, the growth inhibition effect of free gefitinib (not encapsulated) on C6 glioma cells was determined in vitro. The C6 glioma cell line was chosen because it is a well-known and recognized cell line used for subcutaneous tumor studies [24,55,139]. In addition, the C6 cell line has a Biosafety Level 1 rating, low culturing costs, and is reported to express epidermal growth factor receptor (EGFR), the target receptor for gefitinib [139].…”

Section: Discussionmentioning

confidence: 99%

“…The subcutaneous tumor model was chosen because it provides a simplistic and easy to measure model of tumor growth and is a first step for testing of many polymeric microsphere systems [24,44,48,55,63].…”

Section: Discussionmentioning

confidence: 99%

“…[24,27,41,51,52,55,56]. For example, a typical release of 5-FU from PLGA microspheres has a biphasic profile: an initial burst phase in the first day or two followed by a sustained release for 18 days, as shown in Figure 3.1 [36,72].…”

Section: In Vitro Release Of Drugs From Polymeric Microspheresmentioning

confidence: 99%

“…An example of a subcutaneous glioma study was reported by Naraharisetti et al using paclitaxel encapsulated PLGA microspheres [55]. These drug loaded microspheres, formulated either by spray drying or electrohydrodynamic atomization (EHDA), were implanted along the tumor sites of BALB/c nude mice bearing C6 glioma cells subcutaneously.…”

Section: Drug Encapsulated Polymeric Microspheres For Intracranial Tumentioning

confidence: 99%

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Drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy

Floyd

Galperin

Ratner

2015

J Biomedical Materials Res

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Departments of Bioengineering and Chemical EngineeringThe grim prognosis for patients diagnosed with malignant gliomas necessitates the development of new therapeutic strategies for localized and sustained drug delivery to combat tumor drug resistance and regrowth. Here we introduced the novel formulation of drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy (DREAM BIG Therapy) that is applied post-resection. DREAM BIG Therapy consists of three types of microspheres [poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA), and poly(ε-caprolactone) (PCL)] containing various encapsulated chemotherapeutics, suspended in a degradable, aqueous poly(Nisopropylacrylamide) (PNIPAM) solution. The thermoresponsive PNIPAM solution is capable of suspending drug encapsulated microspheres at room temperature which can be "sprayed on" the post-surgical site. The physiological temperature of the treatment site (37°C) would cause PNIPAM solution to solidify and form an adherent gel layer with entrapped microspheres, providing intimate contact with remaining tumor cells. Over time, PLGA (rapid degradation), PLA (medium speed degradation), and then PCL (slow degradation) microspheres would break iv down, releasing their drug payloads in a sequential, multi-drug release directly to the tumor site, addressing cancerous regrowth and tumor drug resistance. This dissertation will address the development of DREAM BIG Therapy, from microsphere formulation to pilot in vivo studies.Initial work focused on developing blank and drug encapsulated microspheres using emulsion techniques. Preliminary studies utilized rhodamine B as a model drug for encapsulation in PLGA, PLA, and PCL particles and optimized formulation parameters to achieve a high encapsulation. Then, gefitinib, IgG, and lomustine were encapsulated in PLGA, PLA, and PCL microspheres, respectively, achieving encapsulation efficiencies greater than 80% and drug loadings greater than 0.3%. The in vitro release of gefitinib and IgG were also studied. Gefitinib released from PLGA microspheres over 40 days while the release of IgG from PLA microspheres was slower, over a year long period.The microsphere-PNIPAM system was tested for aerosolized application ex vivo. The aqueous PNIPAM solution suspended the microspheres and was aerosolized before phase transitioning to an adherent gel layer on the tissue, entrapping the microspheres on the tissue surface. Finally, when tested in vivo, the gefitinib encapsulated PLGA microspheres entrapped in PNIPAM slowed the tumor volume growth of a subcutaneous C6 glioma in comparison to blank PLGA microspheres entrapped in PNIPAM. Overall, this research confirms the potential of DREAM BIG therapy for future use with multiple chemotherapeutics and microsphere types to combat gliomas at a localized site.v

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: In Vitro Release Of Drugs From Polymeric Microspheresmentioning

confidence: 99%

Section: Drug Encapsulated Polymeric Microspheres For Intracranial Tumentioning

confidence: 99%

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Drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy

Floyd

Galperin

Ratner

2015

J Biomedical Materials Res

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“…Polymer discs were prepared as described above and were sterilized by irradiation with 20 kGy CO 60 .The procedure for polymer disc implantation in the rat is described elsewhere [12]. Briefly, anesthetized rats had their heads shaved and were prepared aseptically.…”

Section: Hydroxycamptothecin Concentration Comparison Between Intra-cmentioning

confidence: 99%

Polymer Delivery of Hydroxycamptothecin against C6 Glioma

Hu¹,

Tang²,

Liu³

2014

JCT

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Hydroxycamptothecin is a potent antineoplastic agent that has shown efficacy against multiple tumor lines in vitro. This is the first study to investigate the release, distribution, and efficacy of hydroxycamptothecin which was incorporated into the biodegradable polymer Polylactic Acid (PLA), and implant into brain directly. In vitro release curve generated showed that a large initial release occurred over the first three days and was followed by a steady, but considerably slower rate of release over the next 25 days. After implanting the discs into 40 male SD rats, the animals were followed up to 28 days, where the concentration in brain tissue was far higher than that in peripheral blood at the each of the eight time-points evaluated, and it was also within the therapeutic range for C6 cells tested in vitro. The in vivo efficacy of the discs was evaluated with rats inoculated intracranially with C6 glioma and treated with hydroxycamptothecin polymer compared to intravenous as well as intratumoral injections; the median survival is 21.1, 13.9, 14.9 days, respectively. Given these data, we conclude that the biodegradable polymer PLA releases hydroxycamptothecin, producing tumoricidal levels in brain tissues and prolonging survival in a rat glioma model.

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Synthesis and anticancer activity of ethyl 5‐amino‐1‐N‐substituted‐imidazole‐4‐carboxylate building blocks

Ruzi

Nie

Bozorov

et al. 2021

Archiv der Pharmazie

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A series of 5‐amino‐1‐N‐substituted‐imidazole‐4‐carboxylate building blocks was synthesized and assayed for their antiproliferative potential against human cancer cell lines, including HeLa (cervical), HT‐29, HCT‐15 (colon), A549 (lung), and MDA‐MB‐231 (breast) cells. The preliminary screening results revealed that several derivatives containing alkyl chains at the N‐1 position of the imidazole core demonstrate a certain inhibitory effect on growth and proliferation. A significant effect was observed following ethyl 5‐amino‐1‐dodecyl‐1H‐imidazole‐4‐carboxylate (5e) treatment for 72 h. The IC50 value for HeLa cells was 0.737 ± 0.05 μM, whereas that for HT‐29 cells was 1.194 ± 0.02 μM. Further investigations revealed that 5e significantly inhibited tumor cell colony formation and migration, and it exhibited antiadhesive effects on HeLa cells as well as antitubulin activity along with the induction of early apoptosis of HeLa and HT‐29 cells. In addition, derivative 5e significantly reduced the cell mitochondrial membrane potential in a dose‐dependent manner and induced early apoptosis of HeLa and HT‐29 cells, indicating that 5e may serve as a lead compound for further drug discovery and development.

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In vivo performance of implantable biodegradable preparations delivering Paclitaxel and Etanidazole for the treatment of glioma

Cited by 47 publications

References 18 publications

Drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy

Drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy

Polymer Delivery of Hydroxycamptothecin against C6 Glioma

Synthesis and anticancer activity of ethyl 5‐amino‐1‐N‐substituted‐imidazole‐4‐carboxylate building blocks

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