Liposomal Delivery of a 30-mer Antisense Oligodeoxynucleotide To Inhibit Proopiomelanocortin Expression†

Fresta, Massimo; Chillemi, Rosa; Spampinato, Santi; Sciuto, Sebastiano; Puglisi, Giovanni

doi:10.1021/js9702978

Cited by 13 publications

(7 citation statements)

References 65 publications

(54 reference statements)

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“…This method can generate relatively smaller unilamellar liposomes with high entrapment volumes [80]. Neutral liposomes containing dipalmitoylphosphocholine/cholesterol/dipalmitoyl-DL-α-phosphatidyl-L-serine (4:3:4) could encapsulate as much as 20% of the input dose of ONs [81]. …”

Section: Lipid Nanoparticles Mediated On Deliverymentioning

confidence: 99%

Delivery of oligonucleotides with lipid nanoparticles

Wang

Miao

Satterlee

et al. 2015

Advanced Drug Delivery Reviews

169

119

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Since their inception in the 1980's, oligonucleotide-based (ON-based) therapeutics have been recognized as powerful tools that can treat a broad spectrum of diseases. The discoveries of novel regulatory methods of gene expression with diverse mechanisms of action are still driving the development of novel ON-based therapeutics. Difficulties in the delivery of this class of therapeutics hinder their in vivo applications, which forces drug delivery systems to be a prerequisite for clinical translation. This review discusses the strategy of using lipid nanoparticles as carriers to deliver therapeutic ONs to target cells in vitro and in vivo. A discourse on how chemical and physical properties of the lipid materials could be utilized during formulation and the resulting effects on delivery efficiency constitutes the major part of this review.

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Section: Lipid Nanoparticles Mediated On Deliverymentioning

confidence: 99%

Delivery of oligonucleotides with lipid nanoparticles

Wang

Miao

Satterlee

et al. 2015

Advanced Drug Delivery Reviews

169

119

View full text Add to dashboard Cite

show abstract

“…Trimethyl phosphate (10% in D 2 O) was used as a reference and set at 0.0 ppm. The average number of bilayers (N) was calculated from the following expression: N ϭ 100/(2 ϫ RLOS), where RLOS is the percentage of the relative loss of signal found before and after Mn 2ϩ addition (18). Vesicle fusion experiments.…”

mentioning

confidence: 99%

Ofloxacin-Loaded Liposomes: In Vitro Activity and Drug Accumulation in Bacteria

Furneri¹,

Fresta

Puglisi

et al. 2000

Antimicrob Agents Chemother

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Different ofloxacin-loaded unilamellar vesicles were prepared by the extrusion technique, and their antimicrobial activities were determined in comparison to those of the free drug by means of MIC determinations with both American Type Culture Collection standards and wild-type bacterial strains (six strains of Enterococcus faecalis, seven strains of Escherichia coli, six strains of Staphylococcus aureus, and six strains of Pseudomonas aeruginosa). The accumulation of ofloxacin and liposome-ofloxacin was measured by determining the amount of the drug inside the bacteria as a function of time. Encapsulated fluoroquinolone yielded MICs which were at least twofold lower than those obtained with the free drug. In particular, liposomes made up of dimyristoylphosphatidylcholine-cholesterol-dipalmitoylphosphatidylserine and dimyristoylphosphatidylcholine-cholesterol-dihexadecylphosphate (4:3:4 molar ratio) provided the best improvement in antimicrobial activity against the various bacterial strains investigated. The liposome formulation produced higher intracellular fluoroquinolone concentrations than those achieved simultaneously with the free drug in both E. coli and P. aeruginosa.Since the discovery of the original DNA gyrase inhibitor nalidixic acid, numerous structural modifications have been carried out to the quinolone nucleus to increase antimicrobial activity and improve pharmacokinetic performance (12,22,29,46).The efficacy of fluoroquinolone antibiotics has led to their proposed use for the treatment and prophylaxis of different bacterial diseases: therapy for the respiratory tract, skin structure, and bone and gastrointestinal infections, as well as urinary tract infections (20,21,23,36,41). However, many studies were developed to improve the potency and spectrum, to achieve sustained blood levels, and to reduce as much as possible drug interactions with various metabolic pathways and physiological processes. Particularly, the use of antibiotic "carrier/delivery systems" would result in enhanced concentrations of the antimicrobial agent at the site of infection. In fact, delivery systems can contribute to (i) targeting of the drug to the infected tissues, (ii) increasing intracellular antibiotic concentrations, and (iii) reducing toxicity of potentially toxic drugs resulting from the targeting to the infectious organisms.Liposomes are possible carriers for controlled drug delivery and targeting by the intravenous route. As with most drug carriers, liposomes have been extensively used in an attempt to improve the selective delivery and the therapeutic index of antimicrobial agents (3, 47). Liposomes, artificial phospholipid membranes, are usually produced from naturally occurring, biodegradable, and nontoxic lipids, such as lecithin, cholesterol, and phosphatidylserine.The aim of the study described here was to investigate the antimicrobial activity against and accumulation in bacteria of ofloxacin-loaded liposomes (of different lipid compositions) in comparison to those of free drugs. Our preliminary experi...

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“…Conventional liposomes (like the LpDNA used herein) in biological systems exhibit several benefits for therapeutic delivery, such as high-stability formulations incorporating a constant amount of drug and long-circulating properties leading to successful crossing of vascular barriers [25]. Compared with previous publications showing an encapsulating efficiency of approximately 40%-55% in conventional liposomes [26][27][28], LpDNA had a relatively high entrapment efficiency (72.8%). We specially formulated our liposomes to be positive in charge by using DSPE-PEG-(2000)-amine and the positively charged choline groups of DPPC in order to entrap negatively-charged plasmids.…”

Section: Discussionmentioning

confidence: 87%