Development of PLGA nanoparticles for sustained release of a connexin43 mimetic peptide to target glioblastoma cells

Roberts, Rose; Smyth, J. D.; Will, John; Roberts, Payton; Grek, Christina L.; Ghatnekar, Gautam S.; Sheng, Zhi; Gourdie, Robert G.; Lamouille, Samy; Foster, E. Johan

doi:10.1016/j.msec.2019.110191

Cited by 35 publications

(25 citation statements)

References 35 publications

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“…PLGA formulations for the sustained-delivery of peptides have been widely investigated and utilized to overcome the necessity of frequent administrations of peptides owing to poor pharmacokinetic profiles of macromolecular therapies [33,34]. In this study, the PLGA-based particles for therapeutic peptides were designed by the FDD process to extend the therapeutic action by prolonging the pulmonary absorption of sCT.…”

Section: Release Behavior Of Sct From Plga Particles In Slfmentioning

confidence: 99%

Design and Characterizations of Inhalable Poly(lactic-co-glycolic acid) Microspheres Prepared by the Fine Droplet Drying Process for a Sustained Effect of Salmon Calcitonin

et al. 2020

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The present study aimed to develop inhalable poly (lactic-co-glycolic acid) (PLGA)-based microparticles of salmon calcitonin (sCT) for sustained pharmacological action by the fine droplet drying (FDD) process, a novel powderization technique employing printing technologies. PLGA was selected as a biodegradable carrier polymer for sustained-release particles of sCT (sCT/SR), and physicochemical characterizations of sCT/SR were conducted. To estimate the in vivo efficacy of the sCT/SR respirable powder (sCT/SR-RP), plasma calcium levels were measured after intratracheal administration in rats. The particle size of sCT/SR was 3.6 µm, and the SPAN factor, one of the parameters to present the uniformity of particle size distribution, was calculated to be 0.65. In the evaluation of the conformational structure of sCT, no significant changes were observed in sCT/SR even after the FDD process. The drug release from sCT/SR showed a biphasic pattern with an initial burst and slow diffusion in simulated lung fluid. sCT/SR-RP showed fine inhalation performance, as evidenced by a fine particle fraction value of 28% in the cascade impactor analysis. After the insufflation of sCT samples (40 µg-sCT/kg) in rats, sCT/SR-RP could enhance and prolong the hypocalcemic action of sCT possibly due to the sustained release and pulmonary absorption of sCT. From these observations, the strategic application of the FDD process could be efficacious to provide PLGA-based inhalable formulations of sCT, as well as other therapeutic peptides, to enhance their biopharmaceutical potentials.

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Section: Release Behavior Of Sct From Plga Particles In Slfmentioning

confidence: 99%

Design and Characterizations of Inhalable Poly(lactic-co-glycolic acid) Microspheres Prepared by the Fine Droplet Drying Process for a Sustained Effect of Salmon Calcitonin

et al. 2020

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“…• In vivo: PLGA-NP (Sousa et al, 2019;Ye et al, 2019;Caban-Toktas et al, 2020;Chung et al, 2020), RGD-NP (Ullah et al, 2020), oleic acid NP (Wang H. et al, 2020) • In vitro only: PLGA-NP (Luque-Michel et al, 2019;Ferreira et al, 2020;Roberts et al, 2020), ethyl arachidate (TPLN) (Alves et al, 2020), FONP (Daniel et al, 2019), pSiNPs…”

Section: Use Experimental Setting and Nanoparticle Typementioning

confidence: 99%

“…2019; Shi et al, 2019;Sousa et al, 2019;Ye et al, 2019;Zhang et al, 2019;Zhao et al, 2019;ZhuGe et al, 2019;Alves et al, 2020;Caban-Toktas et al, 2020;Chung et al, 2020;Ferreira et al, 2020;Kazmi et al, 2020;Liang et al, 2020;Martinez-Rovira et al, 2020;Meng et al, 2020;Roberts et al, 2020;Ullah et al, 2020;Wang H. et al, 2020;Wang X. et al, 2020;Xu et al, 2020;Zhu et al, 2020; see Table 3 for examples of ligand targeting in glioma research). Another active targeting method to increase functional specificity of NPs that are used as gene delivery systems is the transcriptional targeting, which can occur at a transcriptional or posttranscriptional level (Golombek et al, 2018).…”

Section: Radiotherapy Enhancermentioning

confidence: 99%

“…Here, the delivered gene includes a tumor-specific promoter (highly functional only in cancer cells), which will secure a well-localized expression of the transgene, limited to occur only inside the cancer cells of interest. Posttranscriptional regulations of the product encoded by the exogenously delivered gene are achieved by controlling RNA splicing, RNA stability, and initiation of the RNA translation once it is present in the cancer cell (Maier-Hauff et al, 2007;Kim et al, 2010;Wegscheid et al, 2014;Cheng Y. et al, 2016;Shen et al, 2017;Yu et al, 2017;Hua et al, 2018;Daniel et al, 2019;Denora et al, 2019;Dufort et al, 2019;Kunoh et al, 2019;Luque-Michel et al, 2019;Ruan et al, 2019;Rego et al, 2019Rego et al, , 2020Shi et al, 2019;Sousa et al, 2019;Ye et al, 2019;Zhang et al, 2019;Zhao et al, 2019;ZhuGe et al, 2019;Alves et al, 2020;Caban-Toktas et al, 2020;Chung et al, 2020;Ferreira et al, 2020;Kazmi et al, 2020;Liang et al, 2020;Martinez-Rovira et al, 2020;Meng et al, 2020;Roberts et al, 2020;Ullah et al, 2020;Wang H. et al, 2020;Wang X. et al, 2020;Xu et al, 2020;Zhu et al, 2020).…”

Section: Radiotherapy Enhancermentioning

confidence: 99%

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Nanoparticles for Stem Cell Therapy Bioengineering in Glioma

Ruiz‐Garcia

Alvarado-Estrada

Krishnan

et al. 2020

Front. Bioeng. Biotechnol.

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Gliomas are a dismal disease associated with poor survival and high morbidity. Current standard treatments have reached a therapeutic plateau even after combining maximal safe resection, radiation, and chemotherapy. In this setting, stem cells (SCs) have risen as a promising therapeutic armamentarium, given their intrinsic tumor homing as well as their natural or bioengineered antitumor properties. The interplay between stem cells and other therapeutic approaches such as nanoparticles holds the potential to synergize the advantages from the combined therapeutic strategies. Nanoparticles represent a broad spectrum of synthetic and natural biomaterials that have been proven effective in expanding diagnostic and therapeutic efforts, either used alone or in combination with immune, genetic, or cellular therapies. Stem cells have been bioengineered using these biomaterials to enhance their natural properties as well as to act as their vehicle when anticancer nanoparticles need to be delivered into the tumor microenvironment in a very precise manner. Here, we describe the recent developments of this new paradigm in the treatment of malignant gliomas.

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“…Cell viability was determined by the MTS cell viability assay (Promega) as described previously (21,30,(55)(56)(57). In brief, to 1,000 cells were plated in the wells of a 96-well plate based upon the cell growth rate.…”

Section: Mts Cell Viability Assaymentioning

confidence: 99%

Connexin 43 confers chemoresistance through activating PI3K

Pridham

Shah

Sheng

et al. 2020

Preprint

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Circumventing chemoresistance is crucial for effectively treating glioblastoma due to limited therapeutic options. The gap junction protein connexin 43 (Cx43) renders glioblastoma resistant to the frontline chemotherapy temozolomide; however, targeting Cx43 is difficult because mechanisms underlying Cx43-mediated chemoresistance remain elusive. Here we show that Cx43, but not other connexins, is highly expressed in glioblastoma and strongly correlates with poor patient prognosis and chemoresistance, making Cx43 the prime therapeutic target among all connexins. The intracellular carboxyl terminus of Cx43 binds to phosphatidylinositol 3-kinase (PI3K) catalytic subunit beta (PIK3CB, also called PI3Kbeta or p110beta), thereby activating PI3K signaling independent of Cx43-channels and subsequently inducing temozolomide resistance. A combination of alphaCT1, a Cx43-targeting peptide inhibitor, and PIK3CB-selective inhibitors restores temozolomide sensitivity in vitro and in vivo. This study not only reveals novel mechanistic insights into chemoresistance in glioblastoma, but also demonstrates that targeting Cx43 and PIK3CB/p110beta is an effective approach for overcoming chemoresistance.

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Development of PLGA nanoparticles for sustained release of a connexin43 mimetic peptide to target glioblastoma cells

Cited by 35 publications

References 35 publications

Design and Characterizations of Inhalable Poly(lactic-co-glycolic acid) Microspheres Prepared by the Fine Droplet Drying Process for a Sustained Effect of Salmon Calcitonin

Design and Characterizations of Inhalable Poly(lactic-co-glycolic acid) Microspheres Prepared by the Fine Droplet Drying Process for a Sustained Effect of Salmon Calcitonin

Nanoparticles for Stem Cell Therapy Bioengineering in Glioma

Connexin 43 confers chemoresistance through activating PI3K

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