Liposomes Assembled from a Dual Drug‐tailed Phospholipid for Cancer Therapy

Abstract

We report a novel dual drug-tailed phospholipid which can form liposomes as a combination of prodrug and drug carrier. An amphiphilic dual chlorambucil-tailed phospholipid (DCTP) was synthesized by a straightforward esterification. With two chlorambucil molecules as hydrophobic tails and one glycerophosphatidylcholine molecule as a hydrophilic head, the DCTP, a phospholipid prodrug, undergoes assembly to form a liposome without any additives by the thin lipid film technique. The DCTP liposomes, as an effective carrier of chlorambucil, exhibited a very high loading capacity and excellent stability. The liposomes had higher cytotoxic effects to cancer cell lines than free DCTP and chlorambucil. The in vivo antitumor activity assessment indicated that the DCTP liposomes could inhibit the tumor growth effectively. This novel strategy of dual drug-tailed phospholipid liposomes may be also applicable to other hydrophobic anticancer drugs which have great potential in cancer therapy.

Tretinoin-loaded liposomal formulations: from lab to comparative clinical study in acne patients

“…Liposomes are microscopic structures consisting of one or more concentric spheres of lipid bilayers enclosing aqueous compartments. Liposomes have been successfully used to encapsulate lipophilic and hydrophilic compounds (Eroglu et al, 2014;Johal et al, 2014;Ali et al, 2014;El-badry et al, 2014;Fang et al, 2015). In the dermatological field, liposomes were used initially only because of their moisturizing and restoring action.…”

Phospholipid prodrug conjugates of insoluble chemotherapeutic agents for ultrasound targeted drug delivery

“…For these prodrugs, the lipid moiety is a member of the bilayer, which is also beneficial for use in lipid monolayer vehicles like microbubbles and nanodroplets [64][65][66][67]. These prodrug structures result in a higher drug loading limit and increased stability than unmodified agents as previously reported [37,58,61,68].…”

“…The lipid prodrugs 2T-P and 2T-N self-assemble into lipid-based particles and require relatively little purification. These drugs can then take advantage of targeting strategies developed for various lipid drug delivery vehicles including active, passive, stealth, and ultrasound triggered release [37]. We incorporated these prodrugs into liposomes, microbubbles, and nanodroplets to experimentally investigate their efficacy; to complement our experimental results we carried out atomistic molecular dynamics simulations of lipid bilayers incorporating the prodrugs.…”

Engineering small molecule nanodrugs to overcome barriers for cancer therapy

“…116 Zwitterionic phospholipid has been widely used to prepare the amphiphilic drug derivatives. [36][37][38][39][40][41][42][43]117,118 For example, artesunate was conjugated to phospholipid form dimeric artesunate phospholipid-based liposomes. Compared to the free drug artesunate, the blood clearance time of zwitterionic liposomes was significantly prolonged.…”