Matches in SemOpenAlex for { <https://semopenalex.org/work/W2189127234> ?p ?o ?g. }
- W2189127234 abstract "Primary brain tumors are a relatively common cause of cancer-related deaths. High-grade gliomas are the most common type of primary brain cancer, and the affected patients have a median survival of less than 1 year. Almost all malignant gliomas are incurable with the present standards of healthcare. Currently accepted therapeutic adjuvants to surgery, such as radiotherapy and chemotherapy, provide only a minor improvement in the disease course and life expectancy for patients diagnosed with malignant gliomas. Often, chemotherapy has failed to make any significant impact on the prognosis of disease because of significant local and systemic toxicity, problems with transport of the drug across the blood brain barrier (BBB), and a high degree of chemoresistance demonstrated by tumor cells. Newer targeted delivery systems with more specificity for gliomas, improved safety profiles, and an enhanced ability to permeate through the BBB are actively under development as the next generation glioma therapies. Blood brain barrier and vascular endothelial cells in and around glioma brain tumors highly express certain receptors such as transferrin for iron transport into brain tumors respectively. To explore the potential of this tumor induced expression of transferrin receptors for targeting drug carriers, in this study, I have developed and characterized liposome carriers containing paclitaxel, for targeted delivery to the glioma brain tumors. A liposome drug delivery system specifically aimed at glioma tumors was designed in this study. Liposomes composed of egg phosphotidylchole (EPC), hydrogenated soybean phosphatidylcholine (HSPC), cholesterol, distearoyl phosphoethanolamine-PEG-2000 conjugate (DSPE-PEG) and DSPE-PEG-biotin were prepared by the lipid film hydration and extrusion process. Transferrin (Tf) with affinity for transferrin receptors over-expressed on blood brain barrier and glioma tumor vasculature were coupled to the distal end of poly ethylene glycol coated long circulating liposomes. The liposome delivery system was characterized in terms of size, lamellarity, ligand density, and drug loading properties. The effect of lipid concentration and type in the formulation on paclitaxel loading in the liposomes was studied. Functional properties of the delivery system were evaluated for, i) in vivo blood circulation time using blood sampling method and also using a novel intravital microscopic method, ii) Selective tumor localization in both flank and intracranial glioma models, and iii) anti-tumor efficacy in mouse flank and intracranial glioma tumors. Further, in order to improve physical and chemical stability of the delivery system and hence enhance its shelf life, a lyophilized formulation and process were developed. Light scattering and electron microscopic observations of the formulations revealed presence of small unilamellar liposomes of about 133 nm in diameter. High performance gel filtration chromatography determinations of ligand coupling to the liposome surface indicated that about 72% of the transferrins were conjugated with biotin groups on the liposome surface. Optimized liposome formulation with 100 mM lipid concentration, 1:33 drug-to-lipid ratio, 5 mol% cholesterol, 5 mol% DSPE-PEG, and 0.01 mol% DSPE-PEG-biotin content yielded 1.3 ± 0.2 mg/mL liposomal paclitaxel with 97.2 ± 3% of the drug being entrapped in the liposomes. These liposomes released no significant amount of the encapsulated drug over 72 hrs at 37°C. Targeted liposomes showed significantly higher rate and extent of tumor accumulation in glioma flank tumors in vivo compared to non-targeted liposomes. Targeted liposomes also possessed long circulating properties with a T1/2 of about 9 hrs in mice. This increased circulation longevity, attributed to steric stabilization effects of PEG, enhanced target accumulation. Near infrared fluorescence imaging demonstrated that these liposomes accumulated selectively in flank tumors with tumor targeting index of 10.59 ± 1.08. Paclitaxel incorporated into the targeted liposomes delayed tumor growth by 7.7 days in 5 doses of 2 mg/Kg body weight. However, no significant tumor growth retardation was observed when paclitaxel was administered in free form (Cremophor EL solubilized form) at similar dose. A process and formulation were developed for freeze-drying the targeted liposome delivery system. Liposome formulations stabilized with 15% sucrose outside the liposomes were able to maintain particle size distribution and drug loading close to initial upon freeze-drying and rehydration. A stable and effective targeted liposome delivery system was developed for paclitaxel to take this drug selectively to glioma brain tumors. This targeted delivery system could potentially improve therapeutic benefits of anticancer drugs with and increase safety when compared to existing solution dosage forms." @default.
- W2189127234 created "2016-06-24" @default.
- W2189127234 creator A5005913826 @default.
- W2189127234 date "2017-10-25" @default.
- W2189127234 modified "2023-09-25" @default.
- W2189127234 title "Development and Evaluation of Brain Tumor Targeted Liposome Delivery System for Paclitaxel" @default.
- W2189127234 cites W12097582 @default.
- W2189127234 cites W1526451509 @default.
- W2189127234 cites W1526790573 @default.
- W2189127234 cites W1545462020 @default.
- W2189127234 cites W1575426508 @default.
- W2189127234 cites W1600453273 @default.
- W2189127234 cites W1641731707 @default.
- W2189127234 cites W1682474579 @default.
- W2189127234 cites W1748218710 @default.
- W2189127234 cites W1867238542 @default.
- W2189127234 cites W19396731 @default.
- W2189127234 cites W1952264151 @default.
- W2189127234 cites W1963482064 @default.
- W2189127234 cites W1967669588 @default.
- W2189127234 cites W1967838912 @default.
- W2189127234 cites W1968603674 @default.
- W2189127234 cites W1970510435 @default.
- W2189127234 cites W1971727309 @default.
- W2189127234 cites W1972334980 @default.
- W2189127234 cites W1973873084 @default.
- W2189127234 cites W1974129665 @default.
- W2189127234 cites W1974687989 @default.
- W2189127234 cites W1979120586 @default.
- W2189127234 cites W1980422006 @default.
- W2189127234 cites W1980637318 @default.
- W2189127234 cites W1981901434 @default.
- W2189127234 cites W1981956388 @default.
- W2189127234 cites W1984752093 @default.
- W2189127234 cites W1985316610 @default.
- W2189127234 cites W1986129921 @default.
- W2189127234 cites W1986144289 @default.
- W2189127234 cites W1989072027 @default.
- W2189127234 cites W1990495912 @default.
- W2189127234 cites W1991354544 @default.
- W2189127234 cites W1992983740 @default.
- W2189127234 cites W1993181868 @default.
- W2189127234 cites W1993342139 @default.
- W2189127234 cites W1993546257 @default.
- W2189127234 cites W199447113 @default.
- W2189127234 cites W1996814032 @default.
- W2189127234 cites W1998762609 @default.
- W2189127234 cites W1999199520 @default.
- W2189127234 cites W2000257842 @default.
- W2189127234 cites W2001107461 @default.
- W2189127234 cites W2001539595 @default.
- W2189127234 cites W2001660159 @default.
- W2189127234 cites W2001842691 @default.
- W2189127234 cites W2004013171 @default.
- W2189127234 cites W2004563219 @default.
- W2189127234 cites W2005296909 @default.
- W2189127234 cites W2005790017 @default.
- W2189127234 cites W2009542460 @default.
- W2189127234 cites W2010207640 @default.
- W2189127234 cites W2016550483 @default.
- W2189127234 cites W2017093750 @default.
- W2189127234 cites W2017425912 @default.
- W2189127234 cites W2017562040 @default.
- W2189127234 cites W2017952116 @default.
- W2189127234 cites W2018109947 @default.
- W2189127234 cites W2022047142 @default.
- W2189127234 cites W2025035152 @default.
- W2189127234 cites W2025104678 @default.
- W2189127234 cites W2026726491 @default.
- W2189127234 cites W2027726692 @default.
- W2189127234 cites W2028568185 @default.
- W2189127234 cites W20305632 @default.
- W2189127234 cites W2031010539 @default.
- W2189127234 cites W2032955513 @default.
- W2189127234 cites W2033428940 @default.
- W2189127234 cites W2033697559 @default.
- W2189127234 cites W2034365190 @default.
- W2189127234 cites W2034685249 @default.
- W2189127234 cites W2035069181 @default.
- W2189127234 cites W2036204973 @default.
- W2189127234 cites W2037877043 @default.
- W2189127234 cites W2038520392 @default.
- W2189127234 cites W2039444865 @default.
- W2189127234 cites W2039478974 @default.
- W2189127234 cites W2040084528 @default.
- W2189127234 cites W2041759339 @default.
- W2189127234 cites W2042080253 @default.
- W2189127234 cites W2042975268 @default.
- W2189127234 cites W2044573147 @default.
- W2189127234 cites W2047459806 @default.
- W2189127234 cites W2048199422 @default.
- W2189127234 cites W2051216519 @default.
- W2189127234 cites W2051340348 @default.
- W2189127234 cites W2053619773 @default.
- W2189127234 cites W2055806535 @default.
- W2189127234 cites W2055943659 @default.
- W2189127234 cites W2057025349 @default.
- W2189127234 cites W2059564760 @default.
- W2189127234 cites W2059877047 @default.
- W2189127234 cites W2060402488 @default.