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Preparation and Characterization of Nanoliposomes for the Entrapment of Bioactive Hydrophilic Globular Proteins
Published on: August 31, 2019
Stabilization of topotecan in low pH liposomes composed of distearoylphosphatidylcholine
1Division of Pharmaceutics, College of Pharmacy, Ohio State University, Columbus 43210-1291.
Abstract:
Topotecan is a promising anticancer agent presently undergoing clinical evaluation worldwide. Topotecan, camptothecin, 9-aminocamptothecin, and CPT-11 have aroused considerable interest in recent years for their ability to halt the growth of a wide range of human tumors. For each analogue an important structural requirement for biological activity is a closed alpha-hydroxy lactone ring moiety. Unfortunately, this functionality hydrolyses rapidly in aqueous solution under physiological conditions (i.e. pH 7 or above), resulting in an inactive carboxylate form of the drug. In this report, we demonstrate that topotecan's half-life in human plasma (pH 7.6) can be enhanced dramatically by packaging the drug within the aqueous, pH 5-adjusted confines of lipid vesicles composed of diasteroylphosphatidylcholine. We have also demonstrated that drug sequestration within the liposomal particles can be efficiently accomplished. Thus, our preliminary experiments suggest that liposomes may be of potential utility for markedly improving the stability of topotecan in circulation.
Insights
Packaging topotecan in liposomes significantly enhances its stability in human plasma. This method protects the anticancer drug
Area of Science:
- Oncology
- Pharmaceutical Sciences
- Drug Delivery
Background:
- Topotecan is a promising anticancer agent with broad-spectrum antitumor activity.
- The efficacy of topotecan and related camptothecins relies on a crucial alpha-hydroxy lactone ring.
- This lactone ring is unstable at physiological pH, rapidly hydrolyzing to an inactive carboxylate form, limiting therapeutic potential.
Purpose of the Study:
- To investigate a novel method for enhancing the stability of topotecan in human plasma.
- To determine if liposomal encapsulation can protect topotecan from hydrolysis under physiological conditions.
Main Methods:
- Topotecan was encapsulated within liposomes composed of diasteroylphosphatidylcholine.
- The pH of the liposomal interior was adjusted to pH 5.
- The stability and half-life of liposome-encapsulated topotecan in human plasma (pH 7.6) were evaluated.
Main Results:
- Liposomal encapsulation dramatically enhanced the half-life of topotecan in human plasma.
- Efficient sequestration of topotecan within the liposomal particles was achieved.
- The pH 5 environment within the liposomes preserved the active lactone form of topotecan.
Conclusions:
- Liposomes demonstrate significant potential for improving the stability and circulation time of topotecan.
- This drug delivery strategy may overcome the limitations posed by topotecan's chemical instability.
- Liposomal topotecan offers a promising approach for enhanced anticancer therapy.
