Abstract
Numerous attempts to overcome the poor water solubility of cam ptothecin (CPT) by various nano drug delivery systems are described in various sources in the literature. However, the results of these approaches may be hampered by the incomplete separation of free CPT from the formulations, and this issue has not been investigated in detail. This study aimed to promote the solubility and continuous delivery of CPT by developing long-lasting liposomes using various weights (M.W. 2000 and 5000 Daltons) of the hydrophilic polymer polyethylene glycol (PEG). Conventional and PEGylated liposomes containing CPT were formulated via the lipid film hydration method (solvent evaporation) using a rotary flash evaporator after optimising various formulation parameters. The following physicochemical characteristics were investigated: surface morphology, particle size, encapsulation efficiency, in vitro release, and formulation stability. Different molecular weights of PEG were used to improve the encapsulation efficiency and particle size. The stealth liposomes prepared with PEG5000 were discrete in shape and with a higher encapsulation efficiency (83 ± 0.4%) and a prolonged rate of drug release (32.2% in 9 h) compared with conventional liposomes (64.8 ± 0.8% and 52.4%, respectively) and stealth liposomes containing PEG2000 (79.00 ± 0.4% and 45.3%, respectively). Furthermore, the stealth liposomes prepared with PEG5000 were highly stable at refrigeration temperature. Significant changes were observed using various pharmacokinetic parameters (mean residence time (MRT), half-life, elimination rate, volume of distribution, clearance, and area under the curve) of stealth liposomes containing PEG2000 and PEG5000 compared with conventional liposomes. The stealth liposomes prepared with PEG5000 showed promising results with a slow rate of release over a long period compared with conventional liposomes and liposomes prepared with PEG2000, with altered tissue distribution and pharmacokinetic parameters.
Highlights
Camptothecin (CPT) is a naturally occurring quinolone alkaloid found in the bark of Camptotheca acuminata and members of the genus Nothapodytes [1]
The CPT-loaded polyethylene glycol (PEG) liposomes were characterised by measuring the encapsulation efficiency and in vitro rate of drug release
Numerous attempts to overcome the poor water solubility of CPT by various nano drug delivery systems are described in various sources in the literature
Summary
Camptothecin (CPT) is a naturally occurring quinolone alkaloid found in the bark of Camptotheca acuminata and members of the genus Nothapodytes [1]. CPT inhibits DNA topoisomerase I via non-covalent interactions, which inhibit the growth of several tumour types. Various studies have revealed that the lactone ring of CPT is essential for its antitumour activity [2]. Two major drawbacks are related to the efficacy of CPT: its poor solubility in water and the instability of the lactone moiety (Figure 1). The lactone ring is converted to its carboxylate form via a pH-dependent reaction, thereby making the drug less active, highly toxic, and poorly bioavailable [3]. Several approaches have been tested to increase the drug’s solubility
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