Hydrogel Matrix Entrapping PLGA-Paclitaxel Microspheres: Drug Delivery with Near Zero-Order Release and Implantability Advantages for Malignant Brain Tumour Chemotherapy

Ranganath, Sudhir H.; Kee, Irene; Krantz, William B.; Chow, Pierce K. H.; Wang, Chi-Hwa

doi:10.1007/s11095-009-9922-2

Cited by 97 publications

(68 citation statements)

References 35 publications

(47 reference statements)

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“…After 21 days of treatment, tumor volumes were reduced by 85% and 78% for paclitaxel-PLGA when compared to a blank control and the free drug form of paclitaxel, respectively [24]. As opposed to Naraharisetti et al, Ranganath et al.…”

Section: Drug Encapsulated Polymeric Microspheres For Intracranial Tumentioning

confidence: 79%

“…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%

“…Reprinted from Journal of Controlled Release, 159/1, Wolinsky et al, Local drug delivery strategies for cancer treatment: Gels, nanoparticles, polymeric films, rods, and wafers, [14][15][16][17][18][19][20][21][22][23][24][25][26]2012, with permission from Elsevier.…”

Section: Figure 11mentioning

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%

“…[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%

See 4 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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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: Drug Encapsulated Polymeric Microspheres For Intracranial Tumentioning

confidence: 79%