Nanoformulation of dual bexarotene-tailed phospholipid conjugate with high drug loading (original) (raw)
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Journal of Drug Delivery Science and Technology, 2019
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Phospholipid-based Nanomicelles in Cancer Nanomedicine
Nanomedicine in Health and Disease, 2011
Tacrolimus, an immunosuppressive agent, has been shown to be an effective treatment against corneal neovascularization (CNV). However, the poor solubility of this compound restricts its clinical application. The goal of this study was to incorporate tacrolimus into phospholipid-bile salt mixed micelles. Methods and Results: Tacrolimus loaded phospholipid-bile salt mixed micelles were prepared, employing three different methods of direct dispersion, thin film hydration, and remote film loading, and the effects of various formulation parameters (type of dispersion medium, phospholipid to bile salt molar ratio, lipid-to-drug (L/D) molar ratio, time of probe sonication, and type of bile salt) on the physicochemical characteristics of the mixed micelles were assessed. Remote film loading method indicated higher efficacy for drug entrapment in comparison to the other methods. Encapsulation of tacrolimus within the micelles increased remarkably by the use of sodium taurocholate (NaTC) as bile salt, higher phospholipid percentage, and increasing the total lipid level. Atomic force microscopy (AFM) studies confirmed the size and size distribution of the mixed micelles and their spherical morphology. It was observed that release of tacrolimus from the micelles was in a controlled manner, without an initial burst. Conclusion: By adjusting process and formulation factors, phospholipid-bile salt mixed micelles with high entrapment efficiency of (99.5%) and controlled release behavior were achieved, which possess great potential to be valuable carriers for ocular delivery of tacrolimus for the treatment of CNV.
Liposomal Formulation of Retinoids Designed for Enzyme Triggered Release
Journal of Medicinal Chemistry, 2010
The design of retinoid phospholipid prodrugs is described based on molecular dynamics simulations and cytotoxicity studies of synthetic retinoid esters. The prodrugs are degradable by secretory phospholipase A 2 IIA and have potential in liposomal drug delivery targeting tumors. We have synthesized four different retinoid phospholipid prodrugs and shown that they form particles in the liposome size region with average diameters of 94-118 nm. Upon subjection to phospholipase A 2 , the lipid prodrugs were hydrolyzed, releasing cytotoxic retinoids and lysolipids. The formulated lipid prodrugs displayed IC 50 values in the range of 3-19 μM toward HT-29 and Colo205 colon cancer cells in the presence of phospholipase A 2 , while no significant cell death was observed in the absence of the enzyme.
An evidence-based review on bexarotene
Tumor Discovery
Bexarotene is a selective retinoid X receptor agonist of utmost clinical importance. The United States Food and Drug Administration has approved this drug for its effects on cutaneous T-cell lymphoma. Bexarotene has shown great potential, demonstrating enhanced therapeutic activity against a plethora of tumor types, both as a single agent and as an adjuvant with other targeted agents. Despite its potential, bexarotene has turned out to be a nostrum, and formulation-related studies that explore its use have not received much emphasis. Poor aqueous solubility and low bioavailability are challenges in developing an appropriate formulation of this drug. In this review, we aim to provide insights into recent research conducted on formulation development, recent pharmacological findings, patents, and future research requisites of bexarotene, based on the literature gathered from authentic web resources and research articles. Bexarotene is a diamond in the rough, as many researchers have n...
Iranian Journal of Pharmaceutical Research : IJPR, 2018
The aim of current study was to investigate the effect of Brij decoration of liposomes on in-vitro and in-vivo characteristics of the nanocarriers. Two hydrophilic Brij surfactants (Brij 35 and Brij 78) with almost similar molecular weight but differing in acyl chain were incorporated into liposomal bilayers at two percentages (5% and 10%). Conventional liposomes (CL) containing egg phosphatidylcholine and cholesterol as well as Brij-enriched liposomal dispersions were prepared and characterized. In-vivo pharmacokinetics of various liposomal formulations and drug solution (six groups) was studied after intravenous administration to rats. Conventional and Brij enriched doxorubicin (DOX) liposomes had small size within 82-97 nm and showed homogenous distribution (PDI < 0.1). Drug encapsulation was higher than 97% in all liposomes. The drug release profiles proved sustained DOX release from various formulations. Based on the results of in-vivo studies, all five liposomes increased d...
Besifloxacin liposomes with positively charged additives for an improved topical ocular delivery
Scientific Reports, 2020
Topical ophthalmic antibiotics show low efficacy due to the well-known physiological defense mechanisms of the eye, which prevents the penetration of exogenous substances. Here, we aimed to incorporate besifloxacin into liposomes containing amines as positively charged additives and to evaluate the influence of this charge on drug delivery in two situations: (i) iontophoretic and (ii) passive treatments. Hypothesis are (i) charge might enhance the electromigration component upon current application improving penetration efficiency for a burst drug delivery, and (ii) positive charge might prolong formulation residence time, hence drug penetration. Liposomes elaborated with phosphatidylcholine (LP PC) or phosphatidylcholine and spermine (LP PC: SPM) were stable under storage at 6 ºC for 30 days, showed mucoadhesive characteristics, and were non-irritant, according to HET-CAM tests. Electron paramagnetic resonance spectroscopy measurements showed that neither the drug nor spermine inco...
Journal of Liposome Research, 2014
To successfully prepare the diclofenac sodium (DS)-loaded solid lipid nanoparticles (SLNs), phospholipid complexes (PCs) technology was applied here to improve the liposolubility of DS. Solid lipid nanoparticles (SLNs) loaded with phospholipid complexes (PCs) were prepared by the modified emulsion/solvent evaporation method. DS could be solubilized effectively in the organic solvents with the existence of phospholipid and apparent partition coefficient of DS in PCs increased significantly. X-ray diffraction analysis suggested that DS in PCs was either molecularly dispersed or in an amorphous form. However, no significant difference was observed between the Fourier transform infrared spectroscopy (FT-IR) spectra of physical mixture and that of PCs. Particles with small sizes, narrow polydispersity indexes and high entrapment efficiencies could be obtained with the addition of PCs. Furthermore, according to the transmission electron microscopy, a core-shell structure was likely to be formed. The presence of PCs caused the change of zeta potential and retarded the drug release of SLNs, which indicated that phospholipid formed multilayers around the solid lipid core of SLNs. Both FT-IR and differential scanning calorimetry analysis also illustrated that some weak interactions between DS and lipid materials might take place during the preparation of SLNs. In conclusion, the model hydrophilic drug-DS can be formulated into the SLNs with the help of PCs.
AAPS PharmSciTech, 2015
The objective of this study was to develop novel docetaxel phospholipid nanoparticles (NDPNs) for intravenous administration. Modified solvent diffusion-evaporation method was adopted in the NDPN preparation. Central composite design (CCD) was employed in the optimization of the critical formulation factor (drug content) and process variable (stirring rate) to obtain NDPNs with 215.53 ± 1.9-nm particle size, 0.329 ± 0.02 polydispersity index (PDI), and 75.41 ± 4.81% entrapment efficiency. The morphological examination by transmission electron microscopy revealed spherical structure composed of a drug core stabilized within the phospholipid shell. Enhanced cell uptake of coumarin-6-loaded phospholipid nanoparticles by MCF-7 cell line indicated NDPN-efficient cell uptake. In vitro hemolysis test confirmed the safety of the phospholipid nanoparticles. NDPNs exhibited increased area under the curve (AUC) and mean residence time (MRT) by 3.0- and 3.3-fold, respectively, in comparison wit...
Organometallics, 2005
Twofold sila-substitution (C/Si exchange) in the saturated ring of the tetrahydronaphthalene skeleton of the RXR-selective retinoid agonist bexarotene (1a) leads to disilabexarotene (1b). Compound 1b was synthesized in a multistep synthesis, starting from 1,2bis(chlorodimethylsilyl)ethane. The identity of 1b was established by elemental analyses and multinuclear NMR studies, and the C/Si analogues 1a and 1b (and an intermediate in the synthesis of 1b) were structurally characterized by single-crystal X-ray diffraction. Furthermore, 1a and 1b were studied for their interaction with retinoid X receptors. Although the twofold sila-substitution of 1a resulted in significant differences in the molecular structures of 1a and 1b, disila-bexarotene (1b) was shown to be a highly potent RXR agonist.
Novel dual VES phospholipid self-assembled liposomes with an extremely high drug loading efficiency
Colloids and surfaces. B, Biointerfaces, 2017
Vitamin E succinate (VES), a unique selective anti-cancer drug, has attracted much attention for its ability to induce apoptosis in various cancer cells. Importantly, it has been reported that VES is largely non-toxic to normal cells. However, poor aqueous solubility and bioavailability extensively restricted its clinical utility. In this report, dual VES phospholipid conjugate (di-VES-GPC) prodrug based liposomes were prepared in order to develop an efficient delivery system for VES. Di-VES-GPC was first synthesized by conjugating VES with l-α-glycerophosphorylcholine (GPC) using N,N'-dicyclohexylcarbodiimide (DCC) as a coupling agent. The di-VES-GPC prodrug was able to self-assemble into liposomes by reverse-phase evaporation method. The structure of the liposomes was characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM) and cryo-TEM. The results showed that di-VES-GPC assembled liposomes were spherical with an average diameter approximately 1...