Development of novel 5-FU-loaded poly(methylidene malonate 2.1.2)-based microspheres for the treatment of brain cancers

Fournier, E; Passirani, Catherine; Colin, Nathalie; Breton, Pascal; Sagodira, Serge; Benoit, Jean‐Pierre

doi:10.1016/s0939-6411(03)00146-2

Cited by 73 publications

(48 citation statements)

References 33 publications

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“…Initial studies were focused on creating blank or non-encapsulating microspheres using the wellestablished emulsion technique [26,[33][34][35][36][37]41]. After optimization of impeller type, smooth, spherical, non-porous microparticles were produced from both double and single emulsions (Figure 2.7).…”

Section: Discussionmentioning

confidence: 99%

“…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]. However, as demonstrated by Fournier et al, this release can be extended by changing several formulation factors [41]. First, the polymer type was changed from PLGA to the slower degrading poly(methylidene malonate 2.1.2) (PMM 2.1.2).…”

Section: In Vitro Release Of Drugs From Polymeric Microspheresmentioning

confidence: 97%

“…As shown in Figure 2.3b, this technique provides a visual method for determining drug distribution within the microsphere, showing piroxicam located in the PLGA microsphere interior [79]. Aside from SEM, particle size can also be measured by laser diffraction [30,36,37,78], sieving and weighing the fractions [31], and a coulter counter [41,[43][44][45][46]. respectively, for temozolomide encapsulated PLGA microspheres [28].…”

Section: Microsphere Formulation and Characterizationmentioning

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%

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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: In Vitro Release Of Drugs From Polymeric Microspheresmentioning

confidence: 97%

Section: Microsphere Formulation and Characterizationmentioning

confidence: 99%

Section: In Vitro Release Of Drugs From Polymeric Microspheresmentioning

confidence: 99%

See 2 more Smart Citations

Drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy

Floyd

Galperin

Ratner

2015

J Biomedical Materials Res

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“…It may lead to high dosage of this drug, which produces serious toxic effects (Johnson et al, 1999). It can be avoided by a controlled release of 5-FU as reported in polypeptide-and polysaccharide-based drug delivery devices (Fournier et al, 2004). However, it was believed that the therapeutic importance of 5-FU and the technological significance of molecular imprinting polymers, which acts as base excipients for the controlled release of drugs with narrow therapeutic index to avoid its side effect due to over concentration of drug within the body at a particular time may further enhance the controlled release of 5-FU.…”

Section: Mips In Oral Therapeutic Applicationsmentioning

confidence: 99%

Molecular imprinted polymers as drug delivery vehicles

Zaidi

2014

Drug Delivery

106

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This review is aimed to discuss the molecular imprinted polymer (MIP)-based drug delivery systems (DDS). Molecular imprinted polymers have proved to possess the potential and also as a suitable material in several areas over a long period of time. However, only recently it has been employed for pharmaceuticals and biomedical applications, particularly as drug delivery vehicles due to properties including selective recognition generated from imprinting the desired analyte, favorable in harsh experimental conditions, and feedback-controlled recognitive drug release. Hence, this review will discuss their synthesis, the reason they are selected as drug delivery vehicles and for their applications in several drug administration routes (i.e. transdermal, ocular and gastrointestinal or stimuli-reactive routes).

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