Short- and Long-Term Stability of Lyophilised Melatonin-Loaded Lecithin/Chitosan Nanoparticles

Abstract

Regular ArticleRecently, attention has been paid to lecithin/chitosan nanoparticles (NPs) as an alternative colloidal carrier system to polymeric nanoparticles, solid lipid nanoparticles, liposomes and nanoemulsions. These nanoparticles were obtained from the supra-molecular self-organising interaction of the negatively charged lipid material lecithin and the positively charged polysaccharide chitosan, without preliminary vesicle formation.1,2) These constitutive materials are favoured due to their well-known characteristics: Chitosan is a biocompatible and biodegradable cationic polysaccharide exhibiting bioadhesive and penetration enhancing properties 3) ; lecithin is a natural lipid mixture of phospholipids, mainly phosphatidylcholine and phosphatidylethanolamine, and is considered a safe and biocompatible excipient that has been frequently used for the preparation of various delivery nanosystems, such as micro-and nanoemulsions, 4) liposomes, 5) micelles 6) and solid lipid nanoparticles. 7)Mucoadhesive lecithin/chitosan NPs were shown to be suitable carriers for lipophilic drugs. NP suspension prepared with Lipoid S45 lecithin with a lecithin-to-chitosan weight ratio of 20 : 1 enhanced melatonin permeability through a Caco-2 cell monolayer compared to its permeability in an aqueous solution, without inducing plasma membrane damage or a decrease in cell viability at the concentration tested. 8) In another study, lecithin/chitosan NP dispersion was shown to increase accumulation of clobetasol-17-propionate in the skin without any significant permeation across the skin, compared to chitosan gel and commercial cream. 9)These findings imply that lecithin/chitosan NPs have great potential to improve the permeation of encapsulated drugs across various biological barriers. However, the overall poor stability of colloidal nanoparticles in an aqueous medium is a significant drawback from a development perspective. Thus, one of the most important challenges in the development of nanoparticles is to achieve long-term stability during storage.Freeze-drying is a well-established approach to increase the chemical and physical stability of colloidal systems over extended time periods. Prior to the freeze-drying process, special excipients are usually added to the formulation to protect the nanoparticles from various stresses generated during the freezing and drying steps. The role of sugars, such as sorbitol, mannitol, trehalose, glucose, sucrose, and lactose, as lyoprotective and/or cryoprotective agents to prevent nanoparticle aggregation and improve the redispersibility of the dry product has been reviewed in the literature. 10) Briefly, stabilisation of materials in sugar glasses has been explained by the formation of a glassy sugar matrix, which acts as a physical barrier between the particles 11) and inhibits diffusion on a relevant time scale. 12) Recently, Zhang et al. reported that sugars such as glucose and trehalose are very effective in preventing particle aggregation and inhibiting leakage of an active ingredie...

Stability of Chitosan—A Challenge for Pharmaceutical and Biomedical Applications

“…Freeze-drying is also considered as a feasible strategy to improve the physicochemical stability of colloidal systems, including chitosan-based microparticulate delivery products over extended time periods [ 87 , 90 ]. Hafner et al ., established a freeze-drying process for melatonin-loaded lecithin/chitosan nanoparticles in order to improve their poor physicochemical stability in aqueous suspension [ 91 ]. After seven months storage, all lyophilisates remained in an amorphous state and the content of entrapped melatonin did not alter.…”

“…A possible destabilizing influence of the freeze-drying process may be overcome by the addition of disaccharides (such as mannitol, sucrose, and trehalose), which protect chitosan material from freezing stress [ 91 ]. However, due to the risk of Maillard reaction and colored products formation, reducing sugars (e.g., lactose, maltose) should not be considered as bioprotectans.…”

Freeze drying of polyelectrolyte complex nanoparticles: Effect of nanoparticle composition and cryoprotectant selection

“…In contrast to mannitol, TRE was an amorphous excipient after the process and yielded the most suitable protective properties (Cegnar et al, 2011). Briefly, stabilisation of materials in sugar glasses has been explained by the formation of a glassy sugar matrix, which acts as a physical barrier between the particles and inhibits the diffusion on a relevant time scale (Allison et al, 2000;Hafner et al, 2011;Molina et al, 2004). Sugar molecules isolate individual particles in the unfrozen fraction, thereby preventing aggregation during freezing (Allison et al, 2000;Rampino et al, 2013).…”

“…Those compounds have been shown to be effective in maintaining the properties of NPs after the lyophilisation process (Anhorn et al, 2008;Holzer et al, 2009). The advantages of trehalose over other sugars include lower hygroscopicity, the absence of internal hydrogen bonds and consequently more flexible formation of hydrogen bonds with NPs, a very low chemical reactivity and, finally, a high glass transition temperature (Abdelwahed et al, 2006;Crowe et al, 1996;Hafner et al, 2011). Apart from trehalose, poly(ethylene glycol) (PEG) polymers have also been used as stabilisers in freeze drying of NPs including chitosan NPs (Rampino et al, 2013), however no systematic study on the influence of molecular weight or branching has been published thus far.…”

Self-Assembled chitosan/phospholipid nanoparticles: from fundamentals to preparation for advanced drug delivery

“…Ever since the SACPNs were proposed and fabricated, the applications of SACPNs in drug delivery systems have been extensively studied. Various active pharmaceutical ingredients (APIs) have been encapsulated with optimized encapsulation efficiency, drug loading, particle sizes and unique characteristics, as summarized in Table 2 (Hafner et al, 2011;Barbieri et al, 2013;Chhonker et al, 2015;Moreno et al, 2015;Clementino, Batger, et al, 2016;Clementino, Pozzoli, et al 2018;Alkholief, 2019;Khan, 2019; Terr on-Mej ıa et al, 2018). Due to the remarkable biocompatible and biodegradable of SACPNs, it can be used as ideal drug vehicles for transdermal, mucosal, ocular and oral drug delivery.…”