Characterization of Drug-Loaded Poly(d,l-lactide) Microspheres

Benita, S.; Benoit, Jean‐Pierre; Puisieux, F.; Thies, Curt

doi:10.1002/jps.2600731215

Cited by 159 publications

(40 citation statements)

References 10 publications

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“…Lipoplexes (2 µg/disk) or naked DNA, were cryopreserved and lyophilized as described above. PLG microspheres were fabricated with an oil-water single emulsion process based on published methods [24]. PLG (400 mg) in dichloromethane (2% w/w) was emulsified in 150mL of 1.5% polyvinyl alcohol and stirred overnight.…”

Section: Encapsulation Of Dna Into Plgmentioning

confidence: 99%

Nerve growth factor expression by PLG-mediated lipofection

Whittlesey

Shea

2006

Biomaterials

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Biomaterials capable of efficient gene delivery provide a fundamental tool for basic and applied research models, such as promoting neural regeneration. We developed a system for the encapsulation and sustained release of plasmid DNA complexed with a cationic lipid and investigated their efficacy using in vitro models of neurite outgrowth. Sustained lipoplex release was obtained for up to 50 days, with rates controlled by the fabrication conditions. Released lipoplexes retained their activity, transfecting 48.2±8.3% of NIH3T3 cells with luciferase activity of 3.97 × 10 7 RLU/ mg. Expression of nerve growth factor (NGF) was employed in two models of neurite outgrowth: PC12 and primary dorsal root ganglia (DRG) co-culture. Polymer-mediated lipofection of PC12 produced bioactive NGF, eliciting robust neurite outgrowth. An EGFP/NGF dual-expression vector identified transfected cells (GFP-positive) while neurite outgrowth verified NGF secretion. A coculture model examined the ability of NGF secretion by an accessory cell population to stimulate DRG neurite outgrowth. Polymer-mediated transfection of HEK293T with an NGF-encoding plasmid induced outgrowth by DRG neurons. This system could be fabricated as implants or nerve guidance conduits to support cellular and tissue regeneration. Combining this physical support with the ability to locally express neurotrophic factors will potentiate regeneration in nerve injury and disease models.

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Section: Encapsulation Of Dna Into Plgmentioning

confidence: 99%

Nerve growth factor expression by PLG-mediated lipofection

Whittlesey

Shea

2006

Biomaterials

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“…The characterization methods are numerous as well. The most widely used procedures to visualize microparticles are conventional light microscopy (LM) and scanning electron microscopy (SEM) [1][2][3][4][5]. Both techniques can be used to determine the shape and outer structure of the microparticles; nevertheless, they both have certain limitations when used for the analysis of the internal structure of such particles.…”

Section: Introductionmentioning

confidence: 99%

Structural analysis of microparticles by confocal laser scanning microscopy

2000

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This study demonstrates the potential of confocal laser scanning microscopy (CLSM) as a characterization tool for different types of microparticles. Microparticles were prepared by various methods including complex coacervation, spray drying, double emulsion solvent evaporation technique, and ionotropic gelation. Protein drugs and particle wall polymers were covalently labeled with a fluorescent marker prior to particle preparation, while low molecular weight drugs were labeled by mixing with a fluorescent marker of similar solubility properties. As was demonstrated in several examples, CLSM allowed visualization of the polymeric particle wall composition and detection of heterogeneous polymer distribution or changes in polymer matrix composition under the influence of the drug. Furthermore, CLSM provides a method for threedimensional reconstruction and image analysis of the microparticles by imaging several coplanar sections throughout the object. In conclusion, CLSM allows the inspection of internal particle structures without prior sample destruction. It can be used to localize the encapsulated compounds and to detect special structural details of the particle wall composition.

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“…Lomustine has already been encapsulated in liposomes for the intravenous treatment of gliomas, in chitosan nanoparticles for the treatment of human lung cancer, in PLA microspheres for leukemia treatment, and in PLA microspheres acting as an embolic agent, causing obstruction in arteries leading to the tumor and allowing for lomustine release [82,83,94,95]. However, reports of lomustine encapsulated in PCL microspheres or a long term release of lomustine greater than three days were not found in the literature.…”

Section: Chemotherapeutic Choicementioning

confidence: 99%

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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Characterization of Drug-Loaded Poly(d,l-lactide) Microspheres

Cited by 159 publications

References 10 publications

Nerve growth factor expression by PLG-mediated lipofection

Nerve growth factor expression by PLG-mediated lipofection

Structural analysis of microparticles by confocal laser scanning microscopy

Drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy

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