Search

Since lipid nanoparticles (LNP) have emerged as a potent drug delivery system, the objective of this study was to develop and optimize a robust high-performance liquid chromatography with charged aerosol detectors (HPLCCAD) method to simultaneously quantify different lipids in LNPs using the analytical quality by design (AQbD) approach. After defining analytical target profile (ATP), critical method attributes (CMAs) were established as a resolution between the closely eluting lipid peaks and the total analysis time. Thus, potential high-risk method parameters were identified through the initial risk assessment. These parameters were screened using Plackett-Burman design, and three critical method parameters (CMPs)-MeOH ratio, flow rate, and column temperature-were selected for further optimization. Box-Behnken design was employed to develop the quadratic models that explain the relationship between the CMPs and CMAs and to determine the optimal operating conditions. Moreover, to ensure the robustness of the developed method, a method operable design region (MODR) was established using the Monte Carlo simulation. The MODR was identified within the probability map, where the risk of failure to achieve the desired CMAs was less than 1%. The optimized method was validated according to the ICH guidelines (linearity: R 2 > 0.995, accuracy: 97.15-100.48% recovery, precision: RSD < 5%) and successfully applied for the analysis of the lipid in the LNP samples. The development of the analytical method to quantify the lipids is essential for the formulation development and quality control of LNP-based drugs since the potency of LNPs is significantly dependent on the compositions and contents of the lipids in the formation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The mixing of conventional and pH-sensitive lipids was exploited to design novel stimuli-responsive liposomes (fliposomes) that could be used for smart drug delivery. We deeply investigated the structural properties of the fliposomes and revealed the mechanisms that are involved in a membrane transformation during a pH change. From ITC experiments we observed the existence of a slow process that was attributed to lipid layers arrangement with changing pH. Moreover, we determined for the first time the pKa value of the trigger-lipid in an aqueous milieu that is drastically different from the methanol-based values reported previously in the literature. Furthermore, we studied the release kinetics of encapsulated NaCl and proposed a novel model of release that involves the physical fitting parameters that could be extracted from the release curves fitting. We have obtained for the first time, the values of pores self-healing times and were able to trace their evolution with changing pH, temperature, the amount of lipid-trigger., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Protein-based therapeutics are an attractive alternative to established therapeutic approaches and represent one of the fastest growing families of drugs. While many of these proteins can be delivered using established formulations, the intrinsic sensitivity of proteins to denaturation sometimes calls for a protective carrier to allow administration. Historically, lipid-based self-assembled structures, notably liposomes, have performed this function. After the discovery of polymersome-based targeted drug-delivery systems, which offer manifold advantages over lipid-based structures, the scientific community expected that such systems would take the therapeutic world by storm. However, no polymersome formulations have been commercialised. In this review article, we discuss key obstacles for the sluggish translation of polymersome-based protein nanocarriers into approved pharmaceuticals, which include limitations imparted by the use of non-degradable polymers, the intricacies of polymersome production methods, and the complexity of the in vivo journey of polymersomes across various biological barriers. Considering this complex subject from a polymer chemist's point of view, we highlight key areas that are worthy to explore in order to advance polymersomes to a level at which clinical trials become worthwhile and translation into pharmaceutical and nanomedical applications is realistic.

Liposomes are highly effective nanocarriers for encapsulating and delivering a wide range of therapeutic cargo. While advancements in liposome design have improved several pharmacological characteristics, an important area that would benefit from further progress involves cellular targeting and entry. In this concept article, we will focus on recent progress utilizing strategies including reversible covalent bonding and caging groups to activate liposomal cell entry. These approaches take advantage of advancements that have been made in complementary fields including molecular sensing and chemical biology and direct this technology toward controlling liposome cell delivery properties. The decoration of liposomes with groups including boronic acids and cyclic disulfides is presented as a means for driving delivery through reaction with functional groups on cell surfaces. Additionally, caging groups can be exploited to activate cell delivery only upon encountering a target stimulus. These approaches provide promising new avenues for controlling cell delivery in the development of next-generation liposomal therapeutic nanocarriers., (© 2022 Wiley-VCH GmbH.)

Liposomes are effective therapeutic delivery nanocarriers due to their ability to encapsulate and enhance the pharmacokinetic properties of a wide range of therapeutics. Two primary areas in which improvement is needed for liposomal drug delivery is to enhance the ability to infiltrate cells and to facilitate derivatization of the liposome surface. Herein, we report a liposome platform incorporating a cyclic disulfide lipid (CDL) for the dual purpose of enhancing cell entry and functionalizing the liposome membrane through thiol-disulfide exchange. In order to accomplish this, CDL-1 and CDL-2, composed of lipoic acid (LA) or asparagusic acid (AA) appended to a lipid scaffold, were designed and synthesized. A fluorescence-based microplate immobilization assay was implemented to show that these compounds enable convenient membrane decoration through reaction with thiol-functionalized small molecules. Additionally, fluorescence microscopy experiments indicated dramatic enhancements in cellular delivery when CDLs were incorporated within liposomes. These results demonstrate that multifunctional CDLs serve as an exciting liposome system for surface decoration and enhanced cellular delivery., (© 2022 Wiley-VCH GmbH.)

Liposomes are versatile three-dimensional, biomaterial-based frameworks that can spatially enclose a variety of organic and inorganic biomaterials for advanced targeted-delivery applications. Implementation of external-stimuli-controlled release of their cargo will significantly augment their wide application for liposomal drug delivery. This paper presents the synthesis of a carbohydrate-derived lipid, capable of changing its conformation depending on the presence of Zn 2+ : an active state in the presence of Zn 2+ ions and back to an inactive state in the absence of Zn 2+ or when exposed to Na 2 EDTA, a metal chelator with high affinity for Zn 2+ ions. This is the first report of a lipid triggered by the presence of a metal chelator. Total internal reflection fluorescence microscopy and a single-liposome study showed that it indeed was possible for the lipid to be incorporated into the bilayer of stable liposomes that remained leakage-free for the fluorescent cargo of the liposomes. On addition of EDTA to the liposomes, their fluorescent cargo could be released as a result of the membrane-incorporated lipids undergoing a conformational change., (© 2021 Wiley-VCH GmbH.)

The advancement of delivery tools for therapeutic agents has brought several novel formulations with increased drug loading, sustained release, targeted delivery, and prolonged efficacy. Amongst the several novel delivery approaches, multivesicular liposome has gained potential interest because this delivery system possesses the above advantages. In addition, this multivesicular liposomal delivery prevents degradation of the entrapped drug within the physiological environment while administered. The special structure of the vesicles allowed successful entrapment of hydrophobic and hydrophilic therapeutic agents, including proteins and peptides. Furthermore, this novel formulation could maintain the desired drug concentration in the plasma for a prolonged period, which helps to reduce the dosing frequencies, improve bioavailability, and safety. This tool could also provide stability of the formulation, and finally gaining patient compliance. Several multivesicular liposomes received approval for clinical research, while others are at different stages of laboratory research. In this review, we have focused on the preparation of multivesicular liposomes along with their application in different ailments for the improvement of the performance of the entrapped drug. Moreover, the challenges of delivering multivesicular vesicles have also been emphasized. Overall, it could be inferred that multivesicular liposomal delivery is a platform of advanced drug delivery with improved efficacy and safety., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Liposomes are the most used drug delivery vehicle and their therapeutic function is closely linked to their lipid composition. Since most liposome characterization is done using bulk techniques, providing only ensemble averages, the lipid composition of all liposomes within the same formulation are typically assumed to be identical. Here we image individual liposomes using confocal microscopy to quantify that liposomal drug delivery formulations, including multiple component mixtures mimicking Doxil, display more than 10-fold variation in their relative lipid composition. Since liposome function is tightly regulated by the physicochemical properties bestowed by the lipid composition, such significant variations could render only a fraction of liposomes therapeutically active. Additionally, we quantified how this degree of compositional inhomogeneity was modulated by liposome preparation method, the saturation state of the membrane lipid, and whether anti-fouling polyethylene glycol (PEG) conjugated lipids were added to the initial lipid mix or inserted after liposome formation. We believe the insights into the factors governing the degree of inhomogeneity offers the possibility for producing more uniform liposomal drug delivery systems, potentially increasing their therapeutic efficacy., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020. Published by Elsevier Ltd.)

Lipid-based delivery systems are an established technology with considerable clinical acceptance and several applications in human. Herein, we report the design, synthesis and evaluation of novel orthoester nucleoside lipids (ONLs) for the modulation of liposome stability. The ONLs contain head groups with 3'-orthoester nucleoside derivatives featuring positive or negative charges. The insertion of the orthoester function in the NL structures allows the formation of pH-sensitive liposomes. ONL-based liposomes can be hydrolyzed to provide nontoxic products, including nucleoside derivatives and hexadecanol. To allow the release to be tunable at different hydrolysis rates, the charge of the polar head structure is modulated, and the head group can be released at a biologically relevant pH. Crucially, when ONLs are mixed with natural phosphocholine lipids (PC), the resultant liposome evolves toward the formation of a hexadecanol/PC lamellar system. Biological evaluation shows that stable nucleic acid lipid particles (SNALPs) formulated with ONLs and siRNAs can effectively enter into tumor cells and release their nucleic acid payload in response to an intracellular acidic environment. This results in a much higher antitumor activity than conventional SNALPs. The ability to use pH-cleavable nucleolipids to control the stability of lipid-based delivery systems represents a promising approach for the intracellular delivery of drug cargos., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A new synthetic methodology for cationic glycolipids using p-aminophenyl-α-D-mannopyranoside (PAPM) and p-aminophenyl-α-D-galactopyranoside (PAPG) with spacer in between the quaternary nitrogen atom and the sugar unit is developed. In addition, a new class of neutral glycolipid conjugates, such as PAPM-lipids or PAPG-lipids conjugates was also synthesized for targeting drugs to receptors. The precipitation-inhibition assay showed that conjugate of PAPM inhibited the concanavalin A and invertase aggregation. This binding inhibition study of a synthesized compound suggests that conjugates of PAPM can be potentially used to target mannose receptors. In addition, a higher transfection was obtained by mixing PAPM with pSV-β-gal reporter gene and incubating with mannose binding protein/receptor expressing A549 cells. The coexistence of both mannose group and a net positive charge may result in improved transfection efficiency in cells expressing mannose binding proteins/receptors., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Camptothecin (CPT) represents a potent anticancer drug. However, its therapeutic use is impaired by both drug solubility, hydrolysis, and protein interactions in vivo. Use of liposomes as a drug-formulation approach could overcome some of these challenges. The aim of this study was to perform a mechanistic study of the incorporation and retention of the lipophilic parent CPT compound in different liposome formulations using radiolabeled CPT and thus to be able to identify promising CPT delivery systems. In this context, we also wanted to establish an appropriate mouse tumor model, in vivo scintigraphic imaging, and biodistribution methodology for testing the most promising formulation. CPT retention in various liposome formulations after incubation in buffer and serum was determined. The HT-29 mouse tumor model, (111)In-labeled liposomes, as well as (3)H-labeled CPT were used to investigate the biodistribution of liposomes and drug. The ability of different liposome formulations to retain CPT in buffer was influenced by lipid concentration and drug/lipid ratio, rather than lipid composition. The tested formulations were cleared from the blood in the following order: CPT solution > CPT liposomes > (111)In-labeled liposomes, and liposomes mainly accumulated in the liver. Lipid composition did not influence CPT retention to the same extent as earlier observed from incorporation studies. The set-up for the biodistribution study works well and is suited for future in vivo studies on CPT liposomes. The biodistribution study showed that liposomes circulated longer than free drug, but premature release of drug from liposomes occurred. Further studies to develop formulations with higher retention potential and prolonged circulation are desired.

Cationic liposomes exhibit a propensity to selectively target tumor-associated blood vessels demonstrating potential value as anti-cancer drug delivery vehicles. Their utility however, is hampered by their biological instability and rapid elimination following i.v. administration. Efforts to circumvent rapid plasma elimination have, to date, focused on decreasing cationic lipid content and incorporating polyethylene glycol (PEG)-modified lipids. In this study we wanted to determine whether highly charged cationic liposomes with surface-associated PEG could be designed to exhibit extended circulation lifetimes, while retaining tumor vascular targeting properties in an HT29 colorectal cancer xenograft model. Cationic liposomes prepared of DSPC, cationic lipids (DODAC, DOTAP, or DC-CHOL), and DSPE-PEG(2000) were studied. Our results demonstrate that formulations prepared with 50 mol% DODAC or DC-CHOL, and 20 mol% DSPE-PEG(2000) exhibited circulation half-lives ranging from 6.5 to 12.5 h. Biodistribution studies demonstrated that DC-CHOL formulations prepared with DSPE-PEG(2000) accumulated threefold higher in s.c. HT29 tumors than its PEG-free counterpart. Fluorescence microscopy studies suggested that the presence of DSPE-PEG(2000) did not adversely affect liposomal tumor vasculature targeting. We show for the first time that it is achievable to design highly charged, highly pegylated (20 mol% DSPE-PEG(2000)) cationic liposomes which exhibit both extended circulation lifetimes and tumor vascular targeting properties., ((c) 2010 Wiley-Liss, Inc. and the American Pharmacists Association)

The utility of using a multifunctional envelope-type nano device (MEND) for delivering a gene to the liver was examined. Lipotrust, a commercially available transfection reagent whose lipid composition is DC6- 14 :DOPE: cholesterol=4 : 3 : 3, was used as a reference. When Lipotrust was administrated intravenously, luciferase activity of the lung was 25 times higher than that of the liver. The luciferase activity of the lung was greatly reduced when a MEND was administered, even though the lipid composition of the lipid envelope was the same in both devices. Furthermore, the luciferase activity of the liver was 5 times higher than that for lipotrust, suggesting that the encapsulation of plasmid DNA (pDNA) in liposomes is more advantageous for delivering pDNA to the liver than complex formation. The isolation of parenchymal cells (PCs) and non-parenchymal cells (NPCs) showed that the MEND system is capable of expressing the luciferase protein more preferentially in NPCs than the lipoplex system. In addition, when the surface was modified with a pH-sensitive fusogenic peptide (GALA) used as a device for endosomal escape, overall liver luciferase activity was greatly enhanced. This suggests that endosomal escape is a limiting step for the MEND system. In the case of the GALA-modified MEND, the luciferase activity of PCs and NPCs was 18 times and 11 times higher than MEND system, while the transfection efficiency of NPCs was significantly higher compared to that of PCs. Collectively, these data show that a GALA-modified MEND prepared with DC6-14 :DOPE: cholesterol represents a promising device for NPCtargeting gene delivery in vivo.

Lipid-based drug formulations are promising systems for improving delivery of drugs to ocular tissues, such as retina. To develop lipid-based systems further, an improved understanding of their pharmacokinetics is required, but high-quality in vivo experiments require a large number of animals, raising ethical and economic questions. In order to expedite in vivo kinetic testing of lipid-based systems, we propose a barcode approach that is based on barcoding liposomes with non-endogenous lipids. We developed and evaluated a liquid-chromatography-mass spectrometry method to quantify many liposomes simultaneously in aqueous humor, vitreous, and neural retina at higher than ±20% precision and accuracy. Furthermore, we showed in vivo suitability of the method in pharmacokinetic evaluation of six different liposomes after their simultaneous injection into the rat vitreal cavity. We calculated pharmacokinetic parameters in vitreous and aqueous humor, quantified liposome concentrations in the retina, and quantitated retinal distribution of the liposomes in the rats. Compared to individual injections of the liposome formulations, the barcode-based study design enabled reduction of animal numbers from 72 to 12. We believe that the proposed approach is reliable and will reduce and refine ocular pharmacokinetic experiments with liposomes and other lipid-based systems. [Display omitted] • A method to quantify many liposome formulations and study their ocular pharmacokinetics within the same animal was developed. • The ocular pharmacokinetics of six barcoded liposomes were successfully evaluated within the same animal. • The barcode lipid method reduced the number of animals required for a pharmacokinetic study from 72 to 12. [ABSTRACT FROM AUTHOR]

Background: The threat of antibiotic resistance of fungal pathogens and the high toxicity of the most effective drugs, polyene macrolides, force us to look for new ways to develop innovative antifungal formulations. Objective: The aim of this study was to determine how the sterol, phospholipid, and flavonoid composition of liposomal forms of polyene antibiotics, and in particular, amphotericin B (AmB), affects their ability to increase the permeability of lipid bilayers that mimic the membranes of mammalian and fungal cells. Methods: To monitor the membrane permeability induced by various polyene-based lipid formulations, a calcein leakage assay and the electrophysiological technique based on planar lipid bilayers were used. Key results: The replacement of cholesterol with its biosynthetic precursor, 7-dehydrocholesterol, led to a decrease in the ability of AmB-loaded liposomes to permeabilize lipid bilayers mimicking mammalian cell membranes. The inclusion of plant flavonoid phloretin in AmB-loaded liposomes increased the ability of the formulation to disengage a fluorescent marker from lipid vesicles mimicking the membranes of target fungi. I–V characteristics of the fungal-like lipid bilayers treated with the AmB phytosomes were symmetric, demonstrating the functioning of double-length AmB pores and assuming a decrease in the antibiotic threshold concentration. Conclusions and Perspectives: The therapeutic window of polyene lipid formulations might be expanded by varying their sterol composition. Polyene-loaded phytosomes might be considered as the prototypes for innovative lipid antibiotic formulations. [ABSTRACT FROM AUTHOR]

Studies on bionanocomposite drug carriers are a key area in the field of active substance delivery, introducing innovative approaches to improve drug therapy. Such drug carriers play a crucial role in enhancing the bioavailability of active substances, affecting therapy efficiency and precision. The targeted delivery of drugs to the targeted sites of action and minimization of toxicity to the body is becoming possible through the use of these advanced carriers. Recent research has focused on bionanocomposite structures based on biopolymers, including lipids, polysaccharides, and proteins. This review paper is focused on the description of lipid-containing nanocomposite carriers (including liposomes, lipid emulsions, lipid nanoparticles, solid lipid nanoparticles, and nanostructured lipid carriers), polysaccharide-containing nanocomposite carriers (including alginate and cellulose), and protein-containing nanocomposite carriers (e.g., gelatin and albumin). It was demonstrated in many investigations that such carriers show the ability to load therapeutic substances efficiently and precisely control drug release. They also demonstrated desirable biocompatibility, which is a promising sign for their potential application in drug therapy. The development of bionanocomposite drug carriers indicates a novel approach to improving drug delivery processes, which has the potential to contribute to significant advances in the field of pharmacology, improving therapeutic efficacy while minimizing side effects. [ABSTRACT FROM AUTHOR]

Functionalized drug delivery systems have been investigated to improve the targetability and intracellular translocation of therapeutic drugs. We developed high functionality and quality lipids that met unique requirements, focusing on the quality of functional lipids for the preparation of targeted nanoparticles using microfluidic devices. While searching for a lipid with high solubility and dispersibility in solvents, which is one of the requirements, we noted that KK-(EK)4-lipid imparts nonspecific cellular association to polyethylene glycol (PEG)-modified (PEGylated) liposomes, such as cell-penetrating peptides (CPPs). We investigated whether KK-(EK)4-lipid, which has a near-neutral charge, is a novel CPP-modified lipid that enhances the intracellular translocation of nanoparticles. However, the cellular association mechanism of KK-(EK)4-lipid is unknown. Therefore, we synthesized (EK)n-lipid derivatives based on the sequence of KK-(EK)4-lipid and determined the sequence sites involved in cellular association. In addition, KK-(EK)4-lipid was applied to extracellular vesicles (EVs) and mRNA encapsulated lipid nanoparticles (mRNA-LNPs). KK-(EK)4-lipid-modified EVs and mRNA-LNPs showed higher cellular association and in vitro protein expression, respectively, compared to unmodified ones. We elucidated KK-(EK)4-lipid to have potential for applicability in the intracellular delivery of liposomes, EVs, and mRNA-LNPs. [ABSTRACT FROM AUTHOR]

The development of new efficient methods for combating serious diseases, among which, oncological and infectious diseases hold a special place, remains to be an urgent challenge of biomedicine and biotechnology. Currently, the efforts of scientists are focused on the search for drug systems that provide high efficiency of treatment with minimal impacts on a human body. The development of this field has led to the creation of stimuli-responsive liposomes that can release an encapsulated drug under a specific stimulus, such as temperature, pH, electromagnetic field, light, etc. Being stimulated, lipid bilayer vesicles change their structure, size, surface charge, or phase state, thus leading to a controlled release of the drug in a specific place of the body, thereby resulting in a more accurate and efficient delivery. This review discusses the current trends in the development of liposome-based stimuli-responsive systems for the controlled delivery of biologically active substances. [ABSTRACT FROM AUTHOR]

Numerous nanotech arenas in therapeutic biology have recently provided a scientific platform to manufacture a considerable swath of unique chemical entities focusing on drugs. Recently, nanoparticulate drug delivery systems have emerged to deliver a specific drug to a specified site. Among all other carriers, lipids possess features exclusive to nanostructured dosage forms. The bioavailability of orally administered drugs is typically negatively affected by their poor water solubility, resulting from the unique chemical moieties introduced. Because of their unique advantages, lipid nanoparticles must become increasingly predictable as a robust delivery mechanism. The enhanced biopharmaceutical properties and significance of lipid‐based targeting technologies such as liposomes, niosomes, solid lipid nanoparticles and micelles are highlighted in this review. Pharmaceutical implications of lipid nanocarriers for the transport and distribution of various therapeutic agents, such as biotechnological products and small pharmaceutical molecules, is a booming topic. Lipid nanoparticles as drug delivery systems have many appealing properties, including high biocompatibility, ease of preparation, tissue specificity, avoidance of reticuloendothelial systems, delayed drug release, scale‐up feasibility, nontoxicity and targeted delivery. The use of lipid nanoparticles to enhance the transport of biopharmaceuticals is currently considered state‐of‐the‐art. Similarly, we critically examine the upcoming guidelines that therapeutic scientists should handle. [ABSTRACT FROM AUTHOR]

Shear forces are involved in many cellular processes and increase remarkably in the case of cardiovascular diseases in the human body. While various stimuli, such as temperature, pH, light, and electromagnetic fields, have been considered for on‐demand release, developing drug delivery systems that are responsive to physiological‐level shear stresses remains as a challenge. For this purpose, liposomes embedded in hydrogel matrices are promising as they can dynamically engage with their environment due to their soft and deformable structure. However, for optimal drug delivery systems, the interaction between liposomes and the surrounding hydrogel matrix, and their response to the shear should be unraveled. Herein, we used unilamellar 1,2‐Dimyristoyl‐sn‐glycero‐3phosphocholine (DMPC) liposomes as drug nanocarriers and polyethylene (glycol) diacrylate (PEGDA) hydrogels having different elasticities, from 1 to 180 Pa, as extracellular matrix (ECM)‐mimetic matrices to understand shear‐triggered liposome discharge from hydrogels. The presence of liposomes provides hydrogels with temperature‐controlled water uptake which is sensitive to membrane microviscosity. By systematically applying shear deformation from linear to nonlinear deformation regimes, the liposome release under transient and cyclic stimuli is modulated. Considering that shear force is commonly encountered in biofluid flow, these results will provide fundamental basis for rational design of shear‐controlled liposomal drug delivery systems. [ABSTRACT FROM AUTHOR]

The review focuses on the lipid based nanocarriers, with special attention paid to natural bioactive payloads. First, micelles and microemulsions are considered as very attractive colloidal nanocontainers that allow for marked improving the solubility of hydrophobic bioactives. Further, liposomal vehicles are reviewed, with both advantages and limitations discussed. Literature assay covers up-to-date information of about last three to five years, although brief background is given on the pioneer works addressing the liposomes and their evolution from bench to bedside. Final part of the review is devoted to the modern modifications of vesicular nanocarriers which can be adapted to specific administration way due to improved targeting properties, permeability, mucoadhesiveness and possibility to cross biological barriers. Therein, such kinds of nanocarriers as transfersomes, niosomes, ethosomes, chitosomes are evaluated; and separate sections focus on the natural based formulations, i.e., phytosomes and invasomes. [ABSTRACT FROM AUTHOR]

According to the WHO, cancer caused almost 10 million deaths worldwide in 2020, i.e., almost one in six deaths. Among the most common are breast, lung, colon and rectal and prostate cancers. Although the diagnosis is more perfect and spectrum of available drugs is large, there is a clear trend of an increase in cancer that ends fatally. A major advance in treatment was the introduction of gentler antineoplastics for targeted therapy–tyrosine kinase inhibitors (TKIs). Although they have undoubtedly revolutionized oncology and hematology, they have significant side effects and limited efficacy. In addition to the design of new TKIs with improved pharmacokinetic and safety profiles, and being more resistant to the development of drug resistance, high expectations are placed on the reformulation of TKIs into various drug delivery lipid-based nanosystems. This review provides an insight into the history of chemotherapy, a brief overview of the development of TKIs for the treatment of cancer and their mechanism of action and summarizes the results of the applications of self-nanoemulsifying drug delivery systems, nanoemulsions, liposomes, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles and nanostructured lipid carriers used as drug delivery systems of TKIs obtained in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Lipid based nanocarriers are one of the most effective drug delivery systems that is evident from the recent COVID-19 mRNA vaccines. The main objective of this study was to evaluate toxicity of six lipid based formulations with three surface charges—anionic, neutral or cationic, to establish certified reference materials (CRMs) for liposomes and siRNA loaded lipid nanoparticles (LNP-siRNA). Cytotoxicity was assessed by a proliferation assay in adherent and non-adherent cell lines. High concentration of three LNP-siRNAs did not affect viability of suspension cells and LNP-siRNAs were non-toxic to adherent cells at conventionally used concentration. Systematic evaluation using multiple vials and repeated test runs of three liposomes and three LNP-siRNA formulations showed no toxicity in HL60 and A549 cells up to 128 and 16 µg/mL, respectively. Extended treatment and low concentration of LNPs did not affect the viability of suspension cells and adherent cells at 96 h. Interestingly, 80% of A549 and HL60 cells in 3D conditions were viable when treated with cationic LNP-siRNA for 48 h. Taken together, anionic, cationic and neutral lipid formulations were non-toxic to cells and may be explored further in order to develop them as drug carriers. [ABSTRACT FROM AUTHOR]

Globally, breast cancer is one of the most prevalent diseases, inducing critical intimidation to human health. Lipid-based nanomaterials have been successfully demonstrated as drug carriers for breast cancer treatment. To date, the development of a better drug delivery system based on lipid nanomaterials is still urgent to make the treatment and diagnosis easily accessible to breast cancer patients. In a drug delivery system, lipid nanomaterials have revealed distinctive features, including high biocompatibility and efficient drug delivery. Specifically, a targeted drug delivery system based on lipid nanomaterials has inherited the advantage of optimum dosage and low side effects. In this review, insights on currently used potential lipid-based nanomaterials are collected and introduced. The review sheds light on conjugation, targeting, diagnosis, treatment, and clinical significance of lipid-based nanomaterials to treat breast cancer. Furthermore, a brighter side of lipid-based nanomaterials as future potential drug delivery systems for breast cancer therapy is discussed. [ABSTRACT FROM AUTHOR]

Due to complicated anatomical and physical properties, targeted drug delivery to ocular tissues continues to be a key challenge for formulation scientists. Various attempts are currently being made to improve the in vivo performance of therapeutic molecules by encapsulating them in various nanocarrier systems or devices and administering them via invasive/non-invasive or minimally invasive drug administration methods. Biocompatible and biodegradable lipid nanoparticles have emerged as a potential alternative to conventional ocular drug delivery systems to overcome various ocular barriers. Lipid-based nanocarrier systems led to major technological advancements and therapeutic advantages during the last few decades of ocular therapy, such as high precorneal residence time, sustained drug release profile, minimum dosing frequency, decreased drug toxicity, targeted site delivery, and, therefore, an improvement in ocular bioavailability. In addition, such formulations can be given as fine dispersion in patient-friendly droppable preparation without causing blurred vision and ocular sensitivity reactions. The unique advantages of lipid nanoparticles, namely, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, and liposomes in intraocular targeted administration of various therapeutic drugs are extensively discussed. Ongoing and completed clinical trials of various liposome-based formulations and various characterization techniques designed for nanoemulsion in ocular delivery are tabulated. This review also describes diverse solid lipid nanoparticle preparation methods, procedures, advantages, and limitations. Functionalization approaches to overcome the drawbacks of lipid nanoparticles, as well as the exploration of new functional additives with the potential to improve the penetration of macromolecular pharmaceuticals, would quickly progress the challenging field of ocular drug delivery systems. [ABSTRACT FROM AUTHOR]

Cancer is a leading cause of death in many countries around the world. However, the efficacy of current treatments available for variety of cancers is considered to be suboptimal due to the pathophysiological challenges associated with the disease which limits the efficacy of the anticancer drugs. Moreover, the vulnerability towards off-target effects and high toxicity also limits the use of drugs for the treatment of cancers. Besides, the biopharmaceutical challenges like poor water solubility and permeability of the drugs, along with the absence of active targeting capability further decreases the utility of drugs in cancer therapy. As a result of these deficiencies, the current therapeutic strategies face noncompliance to patients for providing meaningful benefits after administration. With the advancements in nanotechnology, there has been a paradigm shift in the modalities for cancer treatment with the help of phytomedicine-based nanosized drug delivery systems coupled with variegated surface-engineering strategies for targeted drug delivery. Among these delivery systems, lipid-based nanoparticles are considered as one of the highly biocompatible, efficient and effective systems extensively explored for anticancer drug delivery. These include diverse range of systems including liposomes, nanoemulsions, solid lipid nanoparticles, nanostructured lipidic carriers and supramolecular carriers, which alters pharmacokinetic and biodistribution of the drugs for active targeting to the desired site of action by overcoming the biopharmaceutical challenges associated with anticancer drug delivery. The present review endeavours to provide a comprehensive account on the recent advances in the application of lipid-based nanostructured systems for improving the pharmacotherapeutic performance of phytomedicines for cancer targeting application. [Display omitted] • Phytoconstituents are new emerging therapeutics against cancer. • These molecules can be combined with existing therapeutics for better outcome. • Lipidic vesicles are compatible carriers and mimic the biological membrane. • Nanoengineering in lipidic carriers enhances its efficacy. [ABSTRACT FROM AUTHOR]

A novel method for electroformation of liposomes and phytosomes using copper electrode is described. Liposomes made at 2 V and 10 Hz AC field from L-α-egg-phosphatidylcholine (egg-PC), K. pneumoniae phosphatidylethanolamine, K. pneumoniae polar lipids and E. coli polar lipids on copper electrode were (777.9 ± 118.4), (370.2 ± 100.5), (825.3 ± 21.54), and (281.3 ± 42.3) nm in diameter, respectively. Giant vesicles were formed at 30 V and 10 Hz AC field from polar lipids of K. pneumoniae and E. coli were (106 ± 29.7) and (86 ± 24.3) µm in diameter, respectively. All liposomes were unilamellar as indicated by their unilamellar indices of 50 ± 2, had surface charge comparable to vesicles made from lipid(s) with similar composition and exhibited only 1–2 mol% of oxidized lipids. Cu concentration in the liposomal samples was <1.5 ppm for large unilamellar vesicles (LUVs) and ˂5 ppm for giant unilamellar vesicles (GUVs). The vesicles were stable for >15 d without loss of their size, charge, or unilamellarity. The method was successfully applied to prepare phytosomes from egg-PC and a phytochemical fraction of Dimorphocalyx glabellus, a medicinal plant with anti-diuretic properties. Phytosomes formed were 1000–1500 nm in diameter and exhibited altered fluorescence and absorbance properties compared to the unencapsulated phytochemical. Phytosomes with phytochemical: egg-PC ratio from 0.15 to 1.5 had encapsulation efficiency ranging 90–30%, respectively, and was stable for 1 month. Our method is easy, inexpensive and convenient that will prove to be useful for preparation of liposomes and phytosomes. [ABSTRACT FROM AUTHOR]

In recent years, several studies have shown that the use of solid lipid nanoparticles (SLN) as a colloidal drug delivery system was more advantageous than lipid emulsions, liposomes and polymeric nanoparticles. SLNs have numerous advantages of different nanosystems and rule out many of their drawbacks. Despite the numerous advantages of SLNs, translation from the preclinical formulation to the industrial scale-up is limited. In order to provide a reproducible and reliable method of producing nanoparticles, and thus, obtain an industrial scale-up, several methods of synthesis of nanoparticles by microfluidic have been developed. Microfluidic technique allows a good control and a continuous online synthesis of nanosystems compared to synthesis in bulk, leading to a narrow size distribution, high batch-to-batch reproducibility, as well as to the industrial scale-up feasibility. This work described the optimization process to produce SLNs by microfluidics. The SLNs produced by microfluidics were characterized by complementary optical and morphological techniques and compared with those produced by bulk method. SLNs were loaded with paclitaxel and sorafenib, used as model drugs. The anti-cancer efficiency of the SLNs formulation was estimated with 2D and 3D tumour models of two different cell lines, and the cellular uptake was also studied with fluorescence-assisted measurements. Image, graphical abstract [ABSTRACT FROM AUTHOR]

The present review describes all the aspect of pulmonary drug delivery system and recent advancement. It deals with the delivery of drugs in important disease conditions like asthma, COPD, lung cancer and cystic fibrosis. These disorders required prolonged delivery of the drug through pulmonary route. Various drug loaded lipid formulation like spherulites, lipid nanoparticles, exosomes, solid lipid nanoparticles, nano structured lipid carriers, Janus particles, liposomes, self-micro-emulsifying drug delivery system, lipospheres and RBS derived nanovesicles are discussed. The pulmonary drug delivery system offers important system to deliver the drug to the targeted site. [ABSTRACT FROM AUTHOR]

Preparation of lipid-based drug delivery systems by microfluidics has been increasingly popular, due to the reproducible, continuous and scalable nature of the microfluidic process. Despite exciting development in the field, versatility and superiority of microfluidics over conventional methods still need further evidence, since preparing clinically-relevant sterically stabilised liposomes has been lacking. The present study describes the optimisation of PEGylated liposomal formulations of various rigidity using staggered herringbone micromixer (SHM). The effect of both processing parameters (total flow rate (TFR) and aqueous-to-ethanol flow rate ratio (FRR)) and formulation parameters (lipid components and composition, initial lipid concentration and aqueous media) was investigated and discussed. Liposomal formulations consist of 1,2-dioleoyl- sn -glycero-3-phosphatidylcholine (DOPC), 1,2-dipalmitoyl- sn -glycero-3-phosphatidylcholine (DPPC) or 1,2-distearoyl- sn -glycero-3-phosphatidylcholine (DSPC), with cholesterol and PEGylated lipid (DSPE-PEG 2000) were successfully prepared with the desired size (∼100 nm) and dispersity (<0.2). Doxorubicin was successfully encapsulated in these liposomes at high (>80%) encapsulation efficiency using the pH-gradient remote loading method, illustrating their bilayer integrity and capability as drug delivery systems. We demonstrated that clinically-relevant PEGylated liposomal formulations could be prepared with properties comparable to conventional techniques. Limitations and recommendations on the microfluidic production of PEGylated liposomes were also discussed. [ABSTRACT FROM AUTHOR]

Abstract Melphalan is an efficient chemotherapeutic agent that is currently used to treat retinoblastoma (Rb); however, the inherent risk of immunogenicity and the hazardous integration of this drug in healthy cells is inevitable. MicroRNAs are short non-coding single-stranded RNAs that affect a vast range of biological processes. Previously, we focused on the regulatory role of miR-181a during cancer development and progression. In this manuscript, 171 nm switchable lipid nanoparticles (LNP) co-delivered melphalan and miR-181a with encapsulation efficiencies of 93%. Encapsulation of melphalan in LNP significantly improved its therapeutic efficiency. Gene analysis shows that miR-181a decreases the expression of anti-proliferative gene MAPK1 and anti-apoptotic gene Bcl-2, but significantly increased the expression of pro-apoptotic gene BAX. Our results suggest that the two agents have a complementary effect in reducing the viability of cultured Rb cells (primary and cell line) and decreasing Rb cell counts in an in-vivo xenograft Rb model in rats. Our results suggest that the proposed co-delivery technique significantly increases the therapeutic impact, allows for lower administration of melphalan, and consequently, could minimize the cytotoxic side-effects of this drug. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract In pharmaceutical technology, lipids and polymers are considered pillar excipients for the fabrication of most dosage forms, irrespective of the administration route. They play various roles ranging from support vehicles to release rate modifiers, stabilizers, solubilizers, permeation enhancers and transfection agents. Focusing on selected applications, which were discussed at the Annual Scientific Meeting of the Gattefossé Foundation 2018, this manuscript recapitulates the fundamental roles of these two important classes of excipients, either employed alone or in combination, and provides insight on their functional properties in various types of drug formulations. Emphasis is placed on oral formulations for the administration of active pharmaceutical ingredients with low aqueous solubilities or poor permeation properties. Additionally, this review article covers the use of lipids and polymers in the design of colloidal injectable delivery systems, and as substrates in additive manufacturing technologies for the production of tailor-made dosage forms. [ABSTRACT FROM AUTHOR]

Background: Liposomes are employed as drug delivery vehicles offering a beneficial pharmacokinetic/distribution mechanism for in vivo therapeutics. Therapeutic liposomes can be designed to target specific cell types through the display of epitope-specific targeting peptides on their surface. The majority of peptides are currently attached by chemical modification of lipid constituents. Here we investigate an alternative and novel method of decorating liposomes with targeting ligand, using remotely and spontaneously inserting chimeric tail-anchored membrane (TA) proteins to drug loaded liposomes. Methods and results: An artificial TA protein chimera containing the transmembrane domain from the spontaneously inserting TA protein cytochrome b5 (Cytb5) provided a robust membrane tether for the incorporation of three different targeting moieties into preformed liposomes. The moieties investigated were the transactivator of transcription (TAT) peptide, the EGF-receptor binding sequence GE11 and the placental and tumour homing ligand CCGKRK. In all cases, TA protein insertion neither significantly altered the size of the liposomes nor reduced drug loading. The efficacy of this novel targeted delivery system was investigated using two human cell lines, HeLa M and BeWo. Short term incubation with one ligand-modified TA chimera, incorporating the TAT peptide, significantly enhanced liposomal delivery of the encapsulated carboxyfluorescein reporter. Conclusion: The Cytb5 TA was successfully employed as a membrane anchor for the incorporation of the desired peptide ligands into a liposomal drug delivery system, with minimal loss of cargo during insertion. This approach therefore provides a viable alternative to chemical conjugation and its potential to accommodate a wider range of targeting ligands may provide an opportunity for enhancing drug delivery. [ABSTRACT FROM AUTHOR]

Advancements in the field of liposomal drug carriers have culminated in greatly improved delivery properties. An important aspect of this work entails development of designer liposomes for release of contents triggered by environmental changes. The majority of these systems are driven by chemical reactions in the presence of different stimuli. However, a promising new paradigm instead focuses on molecular recognition events as the impetus for content release. In certain cases, these platforms exploit synthetic lipid switches designed to undergo conformational changes upon binding to target ions or molecules that perturb membrane assembly, thereby triggering cargo release. Examples of this approach reported thus far showcase how rational design of lipid switches can result in dramatic changes in lipid assembly properties. These strategies show great promise for opening up new pathophysiological stimuli that can be harnessed for programmed content release in drug delivery applications. Cell‐type‐specific drug delivery: This concept article describes recent advancements in the development of stimuli‐responsive liposomes specifically driven by synthetic lipid analogs that undergo conformational changes upon binding interactions that trigger the release of entrapped cargo from liposomes. This enables the development of liposomes that release contents in the presence of increased concentrations of specific atomic or molecular species as a novel means for enhancing cell‐type‐specific drug delivery. [ABSTRACT FROM AUTHOR]