Encapsulation of <I>Trans</I>-Dehydrocrotonin in Liposomes: An Enhancement of the Antitumor Activity

Abstract

The aim of this study was the encapsulation of trans-dehydrocrotonin (t-DCTN) and its inclusion complexes with hydropropyl-beta-cyclodextrin (HP-beta-CD) in liposomes to improve t-DCTN antitumor activity. The in vitro kinetic profiles of t-DCTN-loaded liposomes (LD) and t-DCTN:HP-beta-CD-loaded liposomes (LC) were evaluated using the dialysis technique. The antitumor activity of LD and LC were investigated against Sarcoma 180 in Swiss mice. Histopathological and hematological analyses were carried out. The amounts of t-DCTN and t-DCTN:HP-beta-CD inclusion complex encapsulated in liposomes were equivalent to 1 mg of t-DCTN. The encapsulation efficiencies of LD and LC were 95.0 +/- 3.8% and 91.1 +/- 5.6%, respectively. In relation to kinetics, the drug release profiles of t-DCTN are in substantial agreement with the Fickian model. The treatment of animals with LD and LC produced tumor inhibitions of 79.4 +/- 9.6% and 63.5 +/- 5.5%, respectively. The liposomal encapsulation of t-DCTN by entrapment in the phospholipid bilayer increased at twice the antitumor activity. Moreover, the liposomal formulations reduced the hepatotoxicity effect of the drug and no significant hematological toxicity was observed in the treated animals. However, the counting of platelets was slightly decreased. Thus, the results show that the development of liposomal formulations containing t-DCTN or t-DCTN:HP-beta-CD is an important advance for enabling this drug to be use in therapy.

Remote loading of preencapsulated drugs into stealth liposomes

“…Previous attempts to combine cyclodextrin inclusion complexes with liposomes were limited to passive loading of insoluble drugs (65)(66)(67)(68)(69)(70)(71) or active loading of soluble drugs (72). Passive loading often leads to undesirable membrane incorporation, lowering liposome stability, and is much less efficient than active loading.…”

Remote loading of curcumin-in-modified β-cyclodextrins into liposomes using a transmembrane pH gradient

“…17 Moreover, applying chemical modications to this natural active compound can alter it's biological and chemical properties. Since incorporating drug-cyclodextrin complexes into liposomes were limited to passive loading, 3,8,22 modied cyclodextrins, bearing ionizable groups (Fig. S2 †), may act as a promising carrier to actively load water-insoluble drugs in liposomes core, avoiding the drug chemical modication risk.…”

Nanoliposome-Encapsulated Brinzolamide-hydropropyl-β-cyclodextrin Inclusion Complex: A Potential Therapeutic Ocular Drug-Delivery System

“…The presence of cyclodextrin in the aqueous compartment of nanoliposomes would not affect the characteristics of conventional liposomes but prolong drug release compared to conventional liposomes ( Maestrelli et al, 2010 ; Zhang et al, 2015 ). Although a number of studies on DCL systems have been reported ( Dhule et al, 2012 ; Rahman et al, 2012 ; Lapenda et al, 2013 ; Alomrani et al, 2014 ), to date, the therapeutic application of DCL systems as an ocular delivery system remains to be explored.…”