Microparticles developed by electrohydrodynamic atomization for the local delivery of anticancer drug to treat C6 glioma in vitro

Xie, Jingwei; Marijnissen, J.C.M.; Wang, Chi Hwa

doi:10.1016/j.biomaterials.2006.01.034

Cited by 192 publications

(166 citation statements)

References 36 publications

Supporting

Mentioning

160

Contrasting

Order By: Relevance

“…This demonstrates a method for tuning the release profile based on particle size. An initial burst release was not present, characteristic of several other types of polymeric microsphere systems [41,42,46,[52][53][54]. This initial burst is a concern; if too much drug is released at once, a toxic overdose could result.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy

Floyd

Galperin

Ratner

2015

J Biomedical Materials Res

View full text Add to dashboard Cite

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

show abstract

Section: Discussionmentioning

confidence: 99%

“…[24,[51][52][53][54]. Since emulsion methodologies are widely used for microspheres targeted for glioma therapy and are relatively simple to design and carry out, they were used to create the drug encapsulated microspheres presented in this work.…”

Section: Microsphere Formulation and Characterizationmentioning

confidence: 99%

Drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy

Floyd

Galperin

Ratner

2015

J Biomedical Materials Res

View full text Add to dashboard Cite

show abstract

“…Nowadays, electrohydrodynamics is a vast field of science, ranging from sophisticated applications like nano-dispensing by electrospray for biotechnology [130], the local delivery of anticancer drugs to treat C6 glioma in vitro [131] or the development of an EHD motor [132] to fundamental investigations like image analysis of the flow in EHD pumps [133] or microgravity experiments with liquid bridges aboard a space shuttle [134].…”

Section: Dielectrophoresis/electrospraymentioning

confidence: 99%

Can a Century Old Experiment Reveal Hidden Properties of Water?

Fuchs¹

2010

Water

View full text Add to dashboard Cite

Abstract:In 1893 Sir William Armstrong placed a cotton thread between two wine glasses filled with chemically pure water. After applying a high voltage, a watery connection formed, and after some time, the cotton thread was pulled into one of the glasses, leaving a rope of water suspended between the two glasses. Although being a very simple experiment, it is of special interest since it comprises a number of phenomena currently tackled in modern water science like electrolysis-less charge transport and nanobubbles. This work gives some background information about water research in general and describes the water bridge phenomenon from the viewpoint of different fields such as electrohydrodynamics and quantum field theory. It is shown that the investigation of the floating water bridge led to new discoveries about water, both in the macroscopic and microscopic realm -but these were merely "hidden" in that sense that they only become evident upon application of electric fields.

show abstract

“…Finally, high drug encapsulation efficiencies of around 90 per cent have been reported using electrospraying [29,30]. Several research groups have studied the use of electrospraying to prepare polymeric particles for drug-delivery purposes (including [31][32][33]). Drug-loaded microparticles have been produced in sizes ranging between 250 nm and 100 mm depending on the materials used and the processing parameters applied but are most often observed between 1 and 10 mm in diameter [34].…”

mentioning

confidence: 99%

“…These microparticles are typically intended for pulmonary, nasal or systemic delivery for which they have a suitable size [28]. However, they may also be useful for oral delivery, and in fact, most drug molecule studies with electrospraying have been conducted on drugs with low aqueous solubility such as paclitaxel [32] and itraconazole [35] or protein drugs [36], both of which are challenging but desirable classes of drugs to deliver orally. Most studies have reported spherical particles with a smooth surface and narrow particle-size distributions with some control of particle diameter and a drug-release profile following the Higuchi model [34,37].…”

mentioning

confidence: 99%

Release profile and characteristics of electrosprayed particles for oral delivery of a practically insoluble drug

Bohr

Kristensen²,

Dyas³

et al. 2012

J. R. Soc. Interface.

View full text Add to dashboard Cite

acid) (PLGA) microspheres containing celecoxib were prepared via electrospraying, and the influence of three processing parameters namely flow rate, solute concentration and drug loading, on the physico-chemical properties of the particles and the drug-release profile was studied. Microspheres with diameters between 2 and 8 mm were produced and a near-monodisperse size distribution was achieved ( polydispersivity indices of 6-12%). Further, the inner structure of the particles showed that the internal porosity of the particles increased with increasing solvent concentration. X-ray powder diffraction (XRPD) analysis indicated that the drug was amorphous and remained stable after eight months of storage. Drug release was studied in USP 2 (United States Pharmacopeia Dissolution Apparatus 2) dissolution chambers, and differences in release profiles were observed depending on the parametric values. Changes in release rate were found to be directly related to the influence of the studied parameters on particle size and porosity. The results indicate that electrospraying is an attractive technique for producing drug-loaded microspheres that can be tailored towards an intended drug-delivery application. Compared with the more conventional spray-drying process, it provides better control of particle characteristics and less aggregation during particle formation. In particular, this study demonstrated its suitability for preparing capsules in which the drug is molecularly dispersed and released in a sustained manner to facilitate improved bioavailability.

show abstract

Microparticles developed by electrohydrodynamic atomization for the local delivery of anticancer drug to treat C6 glioma in vitro

Cited by 192 publications

References 36 publications

Drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy

Drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy

Can a Century Old Experiment Reveal Hidden Properties of Water?

Release profile and characteristics of electrosprayed particles for oral delivery of a practically insoluble drug

Contact Info

Product

Resources

About