Novel Surface-Modified Nanostructured Lipid Carriers with Partially Deacetylated Water-Soluble Chitosan for Efficient Ocular Delivery

Tian, Baocheng; Luo, Qiuhua; Song, Shuangshuang; Liu, Dandan; Pan, Hao; Zhang, Wenji; He, Ling; Shi-lin, MA; Yang, Xinggang; Pan, Weisan

doi:10.1002/jps.22813

Cited by 46 publications

(18 citation statements)

References 37 publications

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“…23 In each case, an aliquot of NLF was mingled with an equal volume of CP by adding it drop wise under continuous agitation at room temperature (20 °C) for a 30-min incubation.…”

Section: Methodsmentioning

confidence: 99%

Identification and Testing of Novel CARP-1 Functional Mimetic Compounds as Inhibitors of Non-Small Cell Lung and Triple Negative Breast Cancers

Magesh¹,

Somagoni²,

Cheriyan³

et al. 2015

j biomed nanotechnol

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The triple negative breast cancer (TNBCs) and non-small cell lung cancers (NSCLCs) often acquire mutations that contribute to failure of drugs in clinic and poor prognosis, thus presenting an urgent need to develop new and improved therapeutic modalities. Here we report that CARP-1 functional mimetic (CFMs) compounds 4 and 5, and 4.6, a structurally related analog of CFM-4, are potent inhibitors of TNBC and NSCLC cells in vitro. Cell growth suppression by CFM-4 and -4.6 involved interaction and elevated expression of CARP-1/CCAR1 and Death Effector Domain (DED) containing DNA binding (DEDD)2 proteins. Apoptosis by these compounds also involved activation of pro-apoptotic stress-activated kinases p38 and JNK1/2, cleavage of PARP and loss of mitotic cyclin B1. Both the CFMs inhibited abilities of NSCLC and TNBC cells to migrate, invade, and form colonies in suspension, while disrupting tubule formation by the human umbilical vein endothelial cells (HUVECs). Nano-lipid formulation of CFM-4 (CFM-4 NLF) enhanced its serum bioavailability when compared with the free CFM-4. Oral administration of CFM-4 NLF reduced weights and volume of the xenografted tumors derived from A549 NSCLC and MDA-MB-231 TNBC cells. Although no gross tissue or histological toxicities were noticed, the immuno-histochemical analysis revealed increased CARP-1 and DNA fragmentation in tumors of the CFM-4 NLF-treated animals. In conclusion, while stimulation of pro-apoptotic CARP-1 and DEDD2 expression and their binding underscore a novel mechanism of apoptosis transduction by CFM compounds, our proof-of-concept xenograft studies demonstrate therapeutic potential of CFM-4 for TNBC and NSCLC.

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“…23 In each case, an aliquot of NLF was mingled with an equal volume of CP by adding it drop wise under continuous agitation at room temperature (20 °C) for a 30-min incubation.…”

Section: Methodsmentioning

confidence: 99%

Identification and Testing of Novel CARP-1 Functional Mimetic Compounds as Inhibitors of Non-Small Cell Lung and Triple Negative Breast Cancers

Magesh¹,

Somagoni²,

Cheriyan³

et al. 2015

j biomed nanotechnol

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show abstract

“…[19][20][21][22] Briefly, selected amounts of GEN (0.05%, 10 mg), Compritol 888 ATO (1.10%, 220 mg), Miglyol 812 N (0.38%, 75 mg), and Gelucire 44/14 (0.50%, 100 mg) were blended and heated under moderate stirring at 85°C to form a transparent and uniform oil phase. Then, Cremphor ® EL (1.13%, 225 mg) and EPC (0.38%, 750 mg) were dissolved in 20 mL purified water before being heated to 85°C and added dropwise to the oil phase, with magnetic stirring at 600 rpm over a period of 10 minutes.…”

Section: Preparation Of Gen-loaded Nlc (Gen-nlc)mentioning

confidence: 99%

Nanostructured lipid carrier surface modified with Eudragit RS 100 and its potential ophthalmic functions

Zhang¹,

Li²,

Ye³

et al. 2014

IJN

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This study was carried out to evaluate the ocular performance of a cationic Eudragit (EDU) RS 100-coated nanostructured lipid carrier (NLC). The genistein encapsulated NLC (GEN-NLC) was produced using the melt-emulsification technique followed by surface absorption of EDU RS 100. The EDU RS 100 increased the surface zeta potential from −7.46 mV to +13.60 mV, by uniformly forming a spherical coating outside the NLC surface, as shown by transmission electron microscopy images. The EDU RS 100 on the NLC surface effectively improved the NLC stability by inhibiting particle size growth. The obtained EDU RS 100-GEN-NLC showed extended precorneal clearance and a 1.22-fold increase in AUC (area under the curve) compared with the bare NLC in a Gamma scintigraphic evaluation. The EDU RS 100 modification also significantly increased corneal penetration producing a 3.3-fold increase in apparent permeability coefficients (P app ) compared with references. Draize and cytotoxicity testing confirmed that the developed EDU RS 100-GEN-NLC was nonirritant to ocular tissues and nontoxic to corneal cells. These results indicate that the NLC surface modified by EDU RS 100 significantly improves the NLC properties and exhibits many advantages for ocular use.

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“…Biodegradable cationic polymers such as CS have often been used to improve the mucoadhesive properties and cell association of colloidal drug carriers (Tian et al, 2011;Li et al, 2012). It has also been reported that surface modification by a noninoic surfactant increased the cellular association of nanoparticles (Tahara et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Drug delivery to the ocular posterior segment using lipid emulsion via eye drop administration: Effect of emulsion formulations and surface modification

Lin

Tahara

Takeuchi

2013

International Journal of Pharmaceutics

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Novel Surface-Modified Nanostructured Lipid Carriers with Partially Deacetylated Water-Soluble Chitosan for Efficient Ocular Delivery

Cited by 46 publications

References 37 publications

Identification and Testing of Novel CARP-1 Functional Mimetic Compounds as Inhibitors of Non-Small Cell Lung and Triple Negative Breast Cancers

Identification and Testing of Novel CARP-1 Functional Mimetic Compounds as Inhibitors of Non-Small Cell Lung and Triple Negative Breast Cancers

Nanostructured lipid carrier surface modified with Eudragit RS 100 and its potential ophthalmic functions

Drug delivery to the ocular posterior segment using lipid emulsion via eye drop administration: Effect of emulsion formulations and surface modification

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