Bioadhesive liposomes as topical drug delivery systems: molecular and cellular studies

Margalit, Rimona; Okon, Malka; Yerushalmi, Noga; Avidor, Einat

doi:10.1016/0168-3659(92)90083-4

Cited by 32 publications

(38 citation statements)

References 28 publications

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“…MLV were the raw material for the ULV used in our study. MLV composed of PC:PE:CH at mole ratios of 3:1:1, were prepared by the traditional lipid‐film method 33, 34, 35, 36, 37, 38, 51, 52. Briefly, the lipids were dissolved in chloroform‐methanol (3:1 vol/vol), evaporated to dryness under reduced pressure in a rotary evaporator and hydrated by the swelling solution that consisted of buffer alone (PBS) at the pH of 7.2.…”

Section: Methodsmentioning

confidence: 99%

“…The surface modification was carried out on the nt‐LIP, according to our procedures reported previously 33, 34, 35, 36, 37, 38, 51, 52. Briefly, HA was dissolved in water to a final concentration in the range of 2–5 mg/ml and preactivated by incubation with EDC, at pH 4 (controlled by titration with HCl) for 2 hr at 37°C.…”

Section: Methodsmentioning

confidence: 99%

“…Kinetics of drug efflux from the liposomal formulations were studied according to our procedures reported previously 33, 34, 35, 36, 37, 38, 51, 52. Briefly, a suspension of liposomes (0.5–1.0 ml) was placed in a dialysis sac and the sac was immersed in a constantly‐stirred receiver vessel filled with drug‐free buffer (PBS at pH 7.2), at vol 10‐ to 16‐fold that of the sac.…”

Section: Methodsmentioning

confidence: 99%

“…To endow liposomes with high affinity to recognition sites at designated therapeutic targets, we have previously developed “bioadhesive liposomes.” These liposomes are surface‐modified by covalent anchoring of bioadhesive macromolecules, selected from collagen, gelatin, EGF and hyaluronan, to their surface 33, 34, 35, 36, 37, 38. It was shown, in vitro , that the bioadhesive systems, especially the hyaluronan‐liposomes, bind with high affinity to cells and to extracellular matrices carrying the appropriate recognition sites 33, 34, 35, 36, 37, 38. Designed originally for local (topical or regional) administration, we hypothesized that the particular species in which the bioadhesive ligand is the high‐ M r naturally‐occurring hyaluronan, may also be suitable for systemic administration, in particular for tumor chemotherapy.…”

mentioning

confidence: 99%

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Reaction and miscibility of two diepoxides with poly(ethylene terephthalate)

Fenouillot

Hedreul

Forsythe

et al. 2003

J of Applied Polymer Sci

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Poly(ethylene terephthalate) (PET) was meltblended at 270°C with two epoxy monomers, diglycidyl ether of bisphenol A (DGEBA) and 3,4-epoxycyclohexylmethyl-3,4-epoxycyclohexyl carboxylate (ECY). Intermediate proportions of the epoxy in the range of 20 -0.5 wt % were used. If the epoxy monomers were added in a high proportion (10 -20%), a large fraction did not react with PET. Calorimetric experiments showed that the unreacted fractions of both epoxies were miscible with the amorphous phase of the polyester. Only one glass-transition temperature was detected. It was depressed as the epoxy content was increased. The transition was broad when the PET component was crystalline, and it was narrow when the PET component was made amorphous by quenching of the blend. These features were confirmed by dynamic thermal mechanical analysis. As is often the case for crystalline blends, the crystallization and melting temperatures decreased when the proportion of the epoxy was increased. Concerning the reactivity of the epoxy with PET, the behavior differed according to the nature of the epoxy. The DGEBA monomer showed a low reactivity. It was not effective for the chain extension of PET, and no increase in the intrinsic viscosity was observed under the experimental conditions. However, some functionalization of the chain ends may be possible at a high concentration of the epoxy. ECY was more reactive, and the molecular weight of the processed PET increased, although the value of the commercial untreated polyester was not attained.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Reaction and miscibility of two diepoxides with poly(ethylene terephthalate)

Fenouillot

Hedreul

Forsythe

et al. 2003

J of Applied Polymer Sci

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“…This is the first paper (known to the authors) to use miR125a-5p as a standalone therapeutic for HER2+ metastatic breast cancer via a translational nonviral delivery platform. [41][42][43][44][45][46] This MLV solution was allowed to rest overnight at 4 C, and the next day was mechanically extruded using an Mini Extruder Apparatus (Avanti Polar Lipids) maintained at 65-70 C in a stepwise fashion with progressively smaller membrane pore sizes to reach a final unilamellar vesicle (ULV) in the size range of 80-100 nm hydrodynamic diameter. Each membrane size underwent numerous cycles to ensure final product homogeneity.…”

Section: Introductionmentioning

confidence: 99%

Targeted Delivery of MicroRNA125a-5p by Engineered Lipid Nanoparticles for the Treatment of HER2 Positive Metastatic Breast Cancer

Hayward

Francis

Kholmatov

et al. 2016

j biomed nanotechnol

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MicroRNAs (miRNAs) are endogenous regulators of gene expression that play a pivotal role in biological processes spanning from global homeostasis to disease onset and progression. The ability to manipulate and induce cellular reequilibrium of deregulated miRNA expression profiles by inhibition of oncogenic miRNA or overexpression of tumor suppressor miRNA is a promising cancer strategy, but is currently hindered in application by the lack of nonviral delivery systems. Here we present a lipid nanoparticle (LNP) platform surface coated with Hyaluronic Acid (HA) for the delivery of mature tumor suppressor MicroRNA125a-5p to treat HER2 positive metastatic breast cancer. The delivery platform actively targets patient-derived metastatic breast cancer cells (21MT-1) isolated from the metastatic pleural effusion over normal breast tissue via an intrinsic HA-CD44 mediated endocytosis event, and has the ability to escape from the intracellular endolysosomal pathway for potent gene silencing. Knockdown of the HER2 proto-oncogene at the level of transcription and translation was achieved following HA-LNP mediated transfection with MicroRNA125a-5p. In addition, the PI3K/AKT and MAPK hyperactivated signaling pathways, cellular proliferation, and migration potential were also potently suppressed. Furthermore, the therapeutic efficacy of MicroRNA125a-5p by the HA-LNP platform was demonstrated to be significantly improved as compared to a commercial transfection reagent. This study highlights the therapeutic potential of MicroRNA125a-5p as a standalone treatment of HER2+ metastatic breast cancer via a translational nonviral delivery platform. These findings have major implications on future gene therapy regimens for breast cancer.

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Lymphoblastic lymphoma of childhood and the LSA₂‐L₂ protocol

Mora

Filippa

Qin

et al. 2003

Cancer

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The frequent overexpression of the hyaluronan receptors CD44 and RHAMM in cancer cells opens the door for targeting by the naturally‐occurring high‐Mr hyaluronan. This is the first time effective in vivo tumor targeting is reported for mitomycin C (MMC) loaded inside nano‐sized hyaluronan‐liposomes (denoted tHA‐LIP). The severe adverse effects of free MMC made it a rational candidate for an effective targeted carrier. In vitro, loading MMC inside tHA‐LIP increased drug potency 100‐fold, in cells overexpressing, but not in cells underexpressing, hyaluronan receptors. Both types of liposomes were non‐toxic and reduced MMC‐related toxicity in healthy C57BL/6 mice. In 3 tumor models, BALB/c bearing C‐26 solid tumors; C57BL/6 bearing B16F10.9 or (separately) D122 lung metastasis, tHA‐LIP were long‐circulating, 7‐fold and 70‐fold longer than nt‐LIP and free MMC, respectively. tHA‐LIP‐mediated MMC accumulation in tumor‐bearing lungs was 20% of injected dose, compared to 0.6% and 4% with free drug and nt‐LIP, respectively. Tumor‐free lungs showed low accumulation, irrespective of drug formulation. Key indicators of therapeutic responses, tumor progression, metastatic burden and survival, were superior (p < 0.001) in animals receiving MMC‐loaded tHA‐LIP, no treatment, MMC‐loaded nt‐LIP and free drug. In conclusion, tHA‐LIP perform as tumor‐targeted carriers, with promising prospects for treatment of tumors overexpressing hyaluronan receptors. © 2003 Wiley‐Liss, Inc.

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Bioadhesive liposomes as topical drug delivery systems: molecular and cellular studies

Cited by 32 publications

References 28 publications

Reaction and miscibility of two diepoxides with poly(ethylene terephthalate)

Reaction and miscibility of two diepoxides with poly(ethylene terephthalate)

Targeted Delivery of MicroRNA125a-5p by Engineered Lipid Nanoparticles for the Treatment of HER2 Positive Metastatic Breast Cancer

Lymphoblastic lymphoma of childhood and the LSA₂‐L₂ protocol

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Bioadhesive liposomes as topical drug delivery systems: molecular and cellular studies

Cited by 32 publications

References 28 publications

Reaction and miscibility of two diepoxides with poly(ethylene terephthalate)

Reaction and miscibility of two diepoxides with poly(ethylene terephthalate)

Targeted Delivery of MicroRNA125a-5p by Engineered Lipid Nanoparticles for the Treatment of HER2 Positive Metastatic Breast Cancer

Lymphoblastic lymphoma of childhood and the LSA2‐L2 protocol

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Lymphoblastic lymphoma of childhood and the LSA₂‐L₂ protocol