title: Tailored polymer-lipid hybrid nanoparticles for the delivery of drug conjugate: dual strategy for brain targeting.
abstract: The object of the present study was to investigate the glioma targeting propensity of folic acid (F) decorated polymer-lipid hybrid nanoparticles (PLNs) encapsulating cyclo-[Arg-Gly-Asp-D-Phe-Lys] (cRGDfK) modified paclitaxel (PtxR-FPLNs). The prepared PLNs were supposed to bypass the blood-brain barrier (BBB) efficiently and subsequently target integrin rich glioma cells. The developed formulations were characterized for size, shape, drug entrapment efficiency, and in vitro release profile. PtxR-FPLNs demonstrated highest in vitro inhibitory effect, cell apoptosis and cell uptake. Pharmacokinetics and biodistribution studies showed efficacy of PtxR-FPLNs in vivo. In vivo anti-tumor studies clearly revealed that the median survival time for Balb/C mice treated with PtxR-FPLNs (42 days) was extended significantly as compared to PtxR-PLNs (35 days), free PtxR (18 days), Ptx-FPLNs (38 days), Ptx-PLNs (30 days), free Ptx (14 days) and control group (12 days). From the results it can be concluded that the developed dual targeted nanoformulation was able to efficiently cross the BBB and significantly deliver higher amounts of drug to brain tumor for better therapeutic outcome.
authors.affiliation: Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, 470003 Sagar, MP, India. Electronic address: uditaagrawal.pharma@gmail.com.
authors.forename: Udita
authors.initials: U
authors.lastname: Agrawal
authors.affiliation: Cancer Pharmacology Division, Indian Institute of Integrative Medicine, 180001 Jammu, India.
authors.forename: Gousia
authors.initials: G
authors.lastname: Chashoo
authors.affiliation: Cancer Pharmacology Division, Indian Institute of Integrative Medicine, 180001 Jammu, India.
authors.forename: Parduman Raj
authors.initials: PR
authors.lastname: Sharma
authors.affiliation: Cancer Pharmacology Division, Indian Institute of Integrative Medicine, 180001 Jammu, India.
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Cancer Pharmacology Division, Indian Institute of Integrative Medicine, 180001 Jammu, India.
authors.forename: Ajit Kumar
authors.initials: AK
authors.lastname: Saxena
authors.affiliation: Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, 470003 Sagar, MP, India. Electronic address: spvyas54@gmail.com.
authors.forename: S P
authors.initials: SP
authors.lastname: Vyas
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry*; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
chemical_list: D008055:Lipids; D011108:Polymers; D017239:Paclitaxel
keywords: Blood–brain barrier (BBB); Cyclo-[Arg-Gly-Asp-d-Phe-Lys] (cRGDfK); Folic acid; Glioma; Polymer–lipid hybrid nanoparticles (PLNs)