Preparation irinotecan hydrochloride loaded PEGylated liposomes using novel method supercritical fluid and condition optimized by Box–Behnken design

Discover Nano Research Preparation irinotecan hydrochloride loaded PEGylated liposomes using novel method supercritical fluid and condition optimized by Box–Behnken design Misagh Mohammadi1 · Mehrnaz Karimi1 · Farhad Raofie1 Received: 28 May 2024 / Accepted: 23 July 2024 © The Author(s) 2024  OPEN Abstract A semi-synthetic camptothecin derivative known as irinotecan hydrochloride is frequently used to treat colorectal cancer, including colorectal adenocarcinoma and lung cancers involving small cells. Irinotecan has a very short half-life; therefore, continuous infusions are required to keep the drug’s blood levels at therapeutic levels, which could produce cumulative toxicities. Effective delivery techniques, including liposomes, have been developed to address these shortcomings. In this study, a continuous supercritical fluid approach dubbed Expansion Supercritical Fluid into an aqueous solution, in which the pressure decreases rapidly but remains over the critical pressure, is proposed to manufacture polyethylene glycolylated (PEGylated) liposomes carrying irinotecan hydrochloride. To accomplish this, PEGylated liposomes were created using a Box–Behnken design, and the operating parameters (flow rate, temperature, and pressure drop) were optimized. Encapsulation efficiency, mean size, and prepared liposome count were 94.6%, 55 nm, and 758 under ideal circumstances. Additionally, the stability of the PEGylated liposome was investigated during 8 weeks, and also PEGylated liposome-loaded irinotecan release profile was compared to conventional liposomes and free irinotecan, and a constant drug release was seen after the first burst release from liposomes. Keywords Drug delivery systems · Supercritical fluid expansion · Liposomes · Irinotecan · Polyethylene glycol · Response surface methodolog 1 Introduction Nanotechnology has recently begun to develop in various fields, including cosmetics, pharmaceuticals, medicine, food, and environmental research. Most pharmaceutical research has focused on drug delivery systems (DDS). Developing nanocarriers, such as lipid carriers (known as liposomal formulations), is one of the most promising strategies for drug delivery systems, as they significantly improve drug pharmacokinetics and, in turn, reduce toxicity and improve therapeutic efficacy and biocompatibility of drugs [1, 2]. These spherical vesicles are composed of one or more phospholipid bilayers. These carriers are biocompatible because they resemble human cells whose exterior lipid bilayer encloses the aqueous compartment [3, 4]. Supplementary Information The online version contains supplementary material available at https://doi.org/10.1186/s11671-024- 04071-z. * Farhad Raofie, | 1Department of Analytical Chemistry and Pollutants, Shahid Beheshti University, Tehran 1983969411, Iran. Discover Nano (2024) 19:141 | https://doi.org/10.1186/s11671-024-04071-z Vol.:(0123456789) Research Discover Nano (2024) 19:141 | https://doi.org/10.1186/s11671-024-04071-z Moreover, liposomes are advantageous drug carriers because they can constantly release the captured substrates, which include both hydrophilic and hydrophobic substrates [5]. Liposomes can also provide a slow drug release, resulting in long-term drug exposure to tumor cells and improving their efficacy [6]. The mononuclear phagocyte system (MPS), which ingests and eliminates liposomes circulating in the bloodstream, is assumed to be the mechanism by which liposomes are cleared from the body. So, it is especially crucial to prevent capture by the liver’s and spleen’s phagocytic cells to prolong blood circulation time. Chain length, lipid unsaturation, lipid composition, size, and Zeta potential are just a few of the liposome properties that impact how long they circulate through the blood [7–9]. Recent research has shown that some liposome formulations, such as those with a small amount of phospholipid modified by polyethylene glycol (PEG), allow these carriers to remain in the blood for longer periods [5, 10, 11]. Although the specific mechanism of the MPS avoidance phenomenon is unknown, it is thought that the PEG chains, due to their water-binding ability and flexibility, prevent the uptake of opsonizing proteins that guide liposomes to macrophages [12]. Furthermore, PEG can protect liposomes by producing a polymer layer on the liposome surface, increasing the hydrophilicity of the surface, increasing the mutual repulsion between the polymer coating and blood components, and shielding surface charge [13]. Also, through an increased permeability and retention (EPR) effect via a passive targeting mechanism, liposomes modified with polyethylene glycol spontaneously accumulate in solid tumors [1]. PEGylated liposomes offer a desirable platform for enhancing the therapeutic index of a range of anticancer medications [5]. Irinotecan hydrochloride (IRH), a semisynthetic derivative of camptothecin, is frequently used in treating colorectal cancer (CRC) such as colorectal adenocarcinoma and malignancies related to small cells in the lung [14, 15]. IRH has been found to specifically engage with the topoisomerase, which controls DNA topology and carries out several nuclear functions, including DNA replication, recombination, and repair. So, it can prevent DNA replication in tumor cells in the case of CRC [16]. Currently, the use of this substance as a single agent or in combination with other chemotherapeutic drugs is approved for treating colorectal, ovarian, cervical, and small-cell lung cancer [17]. But it has been found that IRH has dosage-dependent side effects such as myelosuppression and severe diarrhea because of the bis-piperidine group, which is known to constitute dose-limiting toxicity and restrict the dose that can be used safely [14, 18]. Furthermore, due to the extremely short half-life of IRH, continuous infusions are necessary to maintain its therapeutically effective blood level, which can lead to cumulative toxicities. Because of these drawbacks, effective delivery strategies can both (a) avoid the hydrolytic conversion of the lactone configuration of the E-ring to an inactive open-ring carboxylate and (b) provide prolonged IRH release have been developed [17]. One of the most efficient drug delivery strategies is the liposomal formulation. Current studies claim that IRH is favorable to effective encapsulation in pharmaceutically viable liposome systems due to its physicochemical properties. These liposomal formulations can decrease IRH in vivo clearance and boost anticancer effectiveness [14]. In 2015, the irinotecan liposome injectable Onivyde received US FDA (Food and Drug Administration) approval to treat patients with advanced pancreatic cancer [17]. Liposomes can be made using several methods, with at least 14 major methods reported. Lipid film hydration, also known as thin-layer evaporation, rehydration-dehydration, reverse-phase evaporation, ethanol injection, French press, ether infusion, (...truncated)