Mechanistic Insight into How PEGylation Reduces the Efficacy of pH-Sensitive Liposomes from Molecular Dynamics Simulations

Mahmoudzadeh, Mohammad; Magarkar, Aniket; Koivuniemi, Artturi; Bunker, Alex

doi:10.1021/acs.molpharmaceut.1c00122

Cited by 12 publications

(5 citation statements)

References 83 publications

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“…This finding indicates that the S CD of the phospholipids in the conjugate was lower than that of cholesterol. But S CD in cholesterol-undecanoate-glucose conjugate is higher than both arbutin and undecane-glucose conjugate, which means, compare with arbutin and undecane-glucose conjugate, the cholesterol-undecanoate-glucose conjugate can make phospholipid bilayers more order and compact [ 56 , 57 ]. It could conclude that PLPC/cholesterol-undecanoate-glucose conjugate liposomes could encapsulate more drugs and stably in vivo deliver drugs to target the brain.…”

Section: Resultsmentioning

confidence: 99%

Establishment and evaluation of glucose-modified nanocomposite liposomes for the treatment of cerebral malaria

et al. 2022

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Cerebral malaria (CM) is a life-threatening neurological complication caused by Plasmodium falciparum. About 627,000 patients died of malaria in 2020. Currently, artemisinin and its derivatives are the front-line drugs used for the treatment of cerebral malaria. However, they cannot target the brain, which decreases their effectiveness. Therefore, increasing their ability to target the brain by the nano-delivery system with brain-targeted materials is of great significance for enhancing the effects of antimalarials and reducing CM mortality. This study used glucose transporter 1 (GLUT1) on the blood–brain barrier as a target for a synthesized cholesterol-undecanoic acid–glucose conjugate. The molecular dynamics simulation found that the structural fragment of glucose in the conjugate faced the outside the phospholipid bilayers, which was conducive to the recognition of brain-targeted liposomes by GLUT1. The fluorescence intensity of the brain-targeted liposomes (na-ATS/TMP@lipoBX) in the mouse brain was significantly higher than that of the non-targeted liposomes (na-ATS/TMP@lipo) in vivo (P < 0.001) after intranasal administration. The infection and recurrence rate of the mice receiving na-ATS/TMP@lipoBX treatment were significantly decreased, which had more advantages than those of other administration groups. The analysis of pharmacokinetic data showed that na-ATS/TMP@lipoBX could enter the brain in both systemic circulation and nasal-brain pathway to treat malaria. Taken together, these results in this study provide a new approach to the treatment of cerebral malaria. Graphical Abstract

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Section: Resultsmentioning

confidence: 99%

Establishment and evaluation of glucose-modified nanocomposite liposomes for the treatment of cerebral malaria

et al. 2022

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“…124 Mahmoudzadeh et al investigated how PEGylation reduces the sensitivity of pH-sensitive liposomes. 125 For this purpose, they modeled bilayered systems composed of dioleoylphosphatidylethanolamine (DOPE) with cholesterol, cholesteryl hemisuccinate in the neutral state (CHS) and in the anionic form (CHSa). The systems were modeled with and without PEGylated DOPE.…”

Section: ■ Lipid-based Drug Formulationsmentioning

confidence: 99%

“…pH-sensitive liposomes have been introduced to disrupt the enzymatic degradation of liposomes, which leads to the degradation of the encapsulated drug(s) after entering to the cell . Mahmoudzadeh et al investigated how PEGylation reduces the sensitivity of pH-sensitive liposomes . For this purpose, they modeled bilayered systems composed of dioleoylphosphatidylethanolamine (DOPE) with cholesterol, cholesteryl hemisuccinate in the neutral state (CHS) and in the anionic form (CHSa).…”

Section: Lipid-based Drug Formulationsmentioning

confidence: 99%

Molecular Dynamics Simulation Studies of Bile, Bile Salts, Lipid-Based Drug Formulations, and mRNA–Lipid Nanoparticles: A Review

et al. 2023

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Lipid-based formulation (LBF) is an effective approach for delivering hydrophobic drugs into the systemic circulation by oral administration. However, much of the physical detail regarding the colloidal behavior of LBFs and their interactions with the contents of the gastrointestinal (GI) environment is not well characterized. Recently, researchers have started to use molecular dynamics (MD) simulations to investigate the colloidal behavior of LBF systems and their interactions with bile and other materials present in the GI tract. MD is a computational method, based on classical mechanics, that simulates the physical movements of atoms and provides atomic-scale information that cannot easily be retrieved using experimental investigations. MD can provide insight into assist the development of drug formulations in a cost and time-effective manner. This review summarizes the application of MD simulation to the study of bile, bile salts, and LBFs and their behavior within the GI environment and also discusses MD simulations of lipid-based mRNA vaccine formulations.

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“…LIPOs were prepared via a thin-film hydration method with subsequent extrusion. A PEGylated lipid was incorporated into the formulation to provide additional stability [42,43]. The composition of prepared formulations and their physicochemical properties are displayed in Table 1.…”

Section: Physicochemical Characterizationsmentioning

confidence: 99%

Lipid-Coated Polymeric Nanoparticles for the Photodynamic Therapy of Head and Neck Squamous Cell Carcinomas

Roschenko,

Ayoub,

Engelhardt

et al. 2023

Pharmaceutics

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Next to alcohol and tobacco abuse, infection with human papillomaviruses (HPVs) is a major risk factor for developing head and neck squamous cell carcinomas (HNSCCs), leading to 350,000 casualties worldwide each year. Limited therapy options and drug resistance raise the urge for alternative methods such as photodynamic therapy (PDT), a minimally invasive procedure used to treat HNSCC and other cancers. We prepared lipid-coated polymeric nanoparticles encapsulating curcumin as the photosensitizer (CUR-LCNPs). The prepared CUR-LCNPs were in the nanometer range (153.37 ± 1.58 nm) and showed an encapsulation efficiency of 92.69 ± 0.03%. Proper lipid coating was visualized using atomic force microscopy (AFM). The CUR-LCNPs were tested in three HPVpos and three HPVneg HNSCC lines regarding their uptake capabilities and in vitro cell killing capacity, revealing a variable but highly significant tumor cell inhibiting effect in all tested HNSCC cell lines. No significant differences were detected between the HPVpos and HPVneg HNSCC groups (mean IC50: (9.34 ± 4.73 µmol/L vs. 6.88 ± 1.03 µmol/L), suggesting CUR-LCNPs/PDT to be a promising therapeutic option for HNSCC patients independent of their HPV status.

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Mechanistic Insight into How PEGylation Reduces the Efficacy of pH-Sensitive Liposomes from Molecular Dynamics Simulations

Cited by 12 publications

References 83 publications

Establishment and evaluation of glucose-modified nanocomposite liposomes for the treatment of cerebral malaria

Establishment and evaluation of glucose-modified nanocomposite liposomes for the treatment of cerebral malaria

Molecular Dynamics Simulation Studies of Bile, Bile Salts, Lipid-Based Drug Formulations, and mRNA–Lipid Nanoparticles: A Review

Lipid-Coated Polymeric Nanoparticles for the Photodynamic Therapy of Head and Neck Squamous Cell Carcinomas

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