Sphingomyelin-cholesterol liposomes significantly enhance the pharmacokinetic and therapeutic properties of vincristine in murine and human tumour models

Abstract

Summary This study reports on the development of a liposomal formulation of vincristine with significantly enhanced stability and biological properties. The in vitro and in vivo pharmacokinetic, tumour delivery and efficacy properties of liposomal vincristine formulations based on sphingomyelin (SM) and cholesterol were compared with liposomes composed of distearoylphosphatidylcholine (DSPC)

In vivo administration of liposomal vincristine sensitizes drug‐resistant human solid tumors

“…In earlier studies, the efficacy of SM/Chol VCR was demonstrated using the murine P388 and the human A431 tumors and indicated that the activity of SM/Chol liposomal VCR was significantly improved compared to that of free drug or VCR encapsulated in DSPC/Chol liposomes. 18,19 Our data are in agreement with these previous results and further add the demonstration that SM/Chol liposomal VCR is effective against multiple different xenograft models and is also active against drug resistant tumors. In particular, in vitro experiments demonstrated that encapsulation in liposomes improved the efficacy of VCR in M14 cells and sensitized the M14/R line to the drug.…”

“…The activation of apoptotic program could be due to the slow release of drug from SM/Chol liposome that maintained sustained intratumoral levels of VCR for a longer time compared to free formulation. 18 In conclusion, our data demonstrate the ability of liposomal to sensitize resistant solid tumors to chemotherapy. These results, together with the promising clinical data, obtained in hematologic tumors suggest the use of liposomal VCR in combination therapies of solid malignancies overexpressing the P170 glycoprotein.…”

“…The SM/Chol liposomal formulation further improves the pharmacokinetic parameters of VCR, producing an increased VCR accumulation in peritoneal ascitic murine P388 tumors and in solid tumors compared to DSPC/Chol liposome VCR. 18,19 The better delivery of VCR to tumors observed after SM/Chol liposomal VCR injection resulted in a higher antitumor efficacy than DSPC/Chol liposome VCR. 18 -20 Early results from a phase II clinical trial that is evaluating liposomal VCR as a treatment for newly diagnosed, previously untreated aggressive, NHL patients showed that patients treated with liposomal VCR in combination with other chemotherapy drugs achieved a 100% response rate (www.inexpharm.com).…”

Acoustically-active microbubbles conjugated to liposomes: Characterization of a proposed drug delivery vehicle

“…Liposomes are membrane-enclosed vesicles composed of a lipid bilayer shell (which can trap hydrophobic and amphipathic drugs) surrounding an aqueous core (which can encapsulate hydrophilic drugs) [19][20][21]. In contrast to microbubbles, liposomes have been shown to efficiently carry drugs such as doxorubicin and vincristine [22][23][24], and intravenous injection of drug-carrying liposomes can increase accumulation at the tumor site by 50 to 100 fold compared to the administration of free drug [25][26][27]. Moreover, monodisperse liposomes can be manufactured with an optimized diameter, typically chosen to be near 100 nm to maximize extravasation from tumor vasculature and fusion with cell membranes.…”

Pharmacokinetic characteristics of vincristine sulfate liposomes in patients with advanced solid tumors

“…Previous studies have demonstrated that the liposomal encapsulation of VCR increased its antitumor efficacy without increasing toxicity [8][9][10][11] . Marqibo ® (Vincristine sulfate liposomes injection, Hana Biosciences, Inc) has been extensively studied for its capability to prolong the pharmacokinetics and subsequent exposure of VCR to cancer cells [5,6,12] , thus increasing its antitumor activity [5,13,14] .…”