Synthesis, Surface-Active Properties, and Anthelmintic Activities of New Cationic Gemini Surfactants Against the Gastrointestinal Nematode, Heligmosomoides polygyrus bakeri, In Vitro

We examined the mechanism of action and compared the anthelmintic efficacy of cysteine proteinases from papaya, pineapple, fig, kiwi fruit and Egyptian milkweed in vitro using the rodent gastrointestinal nematode Heligmosomoides polygyrus. Within a 2 h incubation period, all the cysteine proteinases, with the exception of the kiwi fruit extract, caused marked damage to the cuticle of H. polygyrus adult male and female worms, reflected in the loss of surface cuticular layers. Efficacy was comparable for both sexes of worms, was dependent on the presence of cysteine and was completely inhibited by the cysteine proteinase inhibitor, E-64. LD50 values indicated that the purified proteinases were more efficacious than the proteinases in the crude latex, with purified ficin, papain, chymopapain, Egyptian milkweed latex extract and pineapple fruit extract, containing fruit bromelain, having the most potent effect. The mechanism of action of these plant enzymes (i.e. an attack on the protective cuticle of the worm) suggests that resistance would be slow to develop in the field. The efficacy and mode of action make plant cysteine proteinases potential candidates for a novel class of anthelmintics urgently required for the treatment of humans and domestic livestock.

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In vitro inactivation of surface active properties of pulmonary surfactant by hydrogen peroxide and reversal by catalase. † 1566

Pediatric Research ◽

10.1203/00006450-199704001-01585 ◽

1997 ◽

Vol 41 ◽

pp. 263-263

Author(s):

Min Soo Park ◽

Chul Lee ◽

Jeong Nyun Kim ◽

Ran Namgung ◽

Kook-In Park ◽

...

Keyword(s):

Hydrogen Peroxide ◽

Pulmonary Surfactant ◽

Surface Active Properties ◽

Surface Active

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Ozone-Cleavable Gemini Surfactants. Their Surface-Active Properties, Ozonolysis, and Biodegradability

Langmuir ◽

10.1021/la9907578 ◽

2000 ◽

Vol 16 (2) ◽

pp. 368-373 ◽

Cited By ~ 30

Author(s):

Araki Masuyama ◽

Chikara Endo ◽

Shin-ya Takeda ◽

Masatomo Nojima ◽

Daisuke Ono ◽

...

Keyword(s):

Gemini Surfactants ◽

Surface Active Properties ◽

Surface Active

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Development of Lyophilized Gemini Surfactant-Based Gene Delivery Systems: Influence of Lyophilization on the Structure, Activity and Stability of the Lipoplexes

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j3x60d ◽

2012 ◽

Vol 15 (4) ◽

pp. 548 ◽

Cited By ~ 13

Author(s):

Waleed Mohammed-Saeid ◽

Deborah Michel ◽

Anas El-Aneed ◽

Ronald E Verrall ◽

Nicholas H Low ◽

...

Keyword(s):

Conformational Changes ◽

Gemini Surfactant ◽

Gemini Surfactants ◽

Transfection Efficiency ◽

Gene Transfection ◽

Physiochemical Properties ◽

Cationic Gemini Surfactants ◽

The Stability ◽

In Vitro Transfection

Purpose. Cationic gemini surfactants have been studied as non-viral vectors for gene therapy. Clinical applications of cationic lipid/DNA lipoplexes are restricted by their instability in aqueous formulations. In this work, we investigated the influence of lyophilization on the essential physiochemical properties and in vitro transfection of gemini surfactant-lipoplexes. Additionally, we evaluated the feasibility of lyophilization as a technique for preparing lipoplexes with long term stability. Methods. A gemini surfactant [12-7NH-12] and plasmid DNA encoding for interferon-γ were used to prepare gemini surfactant/pDNA [P/G] lipoplexes. Helper lipid DOPE [L] was incorporated in all formulation producing a [P/G/L] system. Sucrose and trehalose were utilized as stabilizing agents. To evaluate the ability of lyophilization to improve the stability of gemini surfactant-based lipoplexes, four lyophilized formulations were stored at 25˚C for three months. The formulations were analyzed at different time-points for physiochemical properties and in vitro transfection. Results. The results showed that both sucrose and trehalose provided anticipated stabilizing effect. The transfection efficiency of the lipoplexes increased 2-3 fold compared to fresh formulations upon lyophilization. This effect can be attributed to the improvement of DNA compaction and changes in the lipoplex morphology due to the lyophilization/rehydration cycles. The physiochemical properties of the lyophilized formulations were maintained throughout the stability study. All lyophilized formulations showed a significant loss of gene transfection activity after three months of storage. Nevertheless, no significant losses of transfection efficiency were observed for three formulations after two months storage at 25 ˚C. Conclusion. Lyophilization significantly improved the physical stability of gemini surfactant-based lipoplexes compared to liquid formulations. As well, lyophilization improved the transfection efficiency of the lipoplexes. The loss of transfection activity upon storage is most probably due to the conformational changes in the supramolecular structure of the lipoplexes as a function of time and temperature rather than to DNA degradation. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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