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Bone metastasis remains a clinical challenge and is still considered incurable. While nanoparticles-based drug delivery and photothermal therapy (PTT) show promise in treating subcutaneous solid tumor, their therapeutic outcome in treating bone metastasis is limited, due to the inaccessibility of bone metastatic site and the complexity of bone metastasis. Herein, we reported a simple nanoplatform composed of thermo-sensitive liposomes (TSL) and gold nanorods (GNR) to treat bone metastasis through improved chemotherapy combined with GNR-assisted PTT. Lipid combination of TSL was firstly tailored to regulate its stability under physiological condition as well as its sensitivity in responding to PTT-caused mild hyperthermia. The obtained TSL with loaded drug was then combined with GNR to form the nanoplatform through unsophisticated incubation. Cell experiments revealed that upon near-infrared (NIR) irradiation, the nanoplatform effectively inhibited the viability and migration ability of tumor cells through PTT, PTT-triggered thermo-sensitive drug release, and PTT-augmented sensitivity of tumor cells to drug. In a murine model of bone metastasis, the nanoplatform enabled effective delivery of loaded drug and GNR to bone metastatic site for rapid drug release upon local NIR irradiation. Through killing tumor cells and rebalancing the turnover of osteoclasts and osteoblasts, the nanoplatform largely preserved bone structure for pain relief and survival extension. Inspired by the simplicity of nanoplatform acquirement and treatment operation, the strategy of liposomes-based thermo-sensitive drug delivery in combination with GNR-assisted PTT is considered greatly promising in treating bone metastasis.

A frequently debated topic related to the origin of life centers around the question of how complex forms of life on today's Earth may have evolved over time from simpler predecessors. For example, the question of how proton concentration gradients across cellular membranes developed in ancestral protocells remains unanswered. This process, which is indispensable for the generation of chemical energy in modern organisms, is driven by energy derived from redox processes in the respiratory chain. Since it is highly unlikely that the complex machinery of the respiratory chain was available on early Earth, we provide an example of how proton gradients can be established in less complex systems. Utilizing liposomes as models of primitive cells, we were able to generate proton gradients of about two pH units across the liposome bilayers using redox reactions as the driving force. Electrons were transferred from sodium sulfite present on the outside of the liposomes to ferricyanide, which was trapped on the inside. A lipid-soluble phenazine derivative served as a shuttle that transferred both electrons and protons across the lipid bilayer. Because sulfite would have been an abundant reduced solute available to the earliest cells, we propose that it may have been a primary source of redox energy for primitive chemiosmotic energy transduction.

Acne vulgaris is a common dermatologic disorder that affects approximately 85% of teenagers, which significantly impacts the quality of life in adolescents. It is a chronic disease of the sebaceous follicles that is multifactorial in etiology. Topical treatment is the first choice for mild and moderate acne, while systemic therapy is reserved for severe and certain moderate cases. Topical treatments include retinoids (e.g., tretinoin and adapalene), antibiotics (e.g., clindamycine), and other agents (e.g., benzoyl peroxide and azelaic acid), often applied in combination. The mechanisms of action include antimicrobial, anti-inflammatory, and keratolytic activities, as well as sebum secretion reduction, and the normalization of follicular keratinization. However, these topical agents commonly induce side effects, such as dryness, burning, stinging, peeling, redness, erythema, and photosensitivity. Therefore, there is a need to reduce the side effects of anti-acne drugs, while maintaining or enhancing their therapeutic effectiveness. This article aims to comprehensively outline nanotechnology strategies, particularly the use of phospholipid-based nanocarriers like liposomes and related vesicles, to enhance therapeutic efficacy, skin tolerability, and patient compliance in the treatment of acne vulgaris. In addition, novel active ingredients encapsulated in vesicles beyond those recommended in official guidelines are discussed.

BackgroundBreast cancer is the second leading cause of death in women, with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) as the two most common forms of invasive breast cancer. While estrogen receptor positive (ER+) IDC and ILC are treated similarly, the multifocality of ILC presents challenges in detection and treatment, worsening long-term clinical outcomes in patients. With increasing documentation of chemoresistance in ILC, additional treatment options are needed. Oncolytic adenoviral therapy may be a promising option, but cancer cells must express the coxsackievirus & adenovirus receptor (CAR) for adenoviral therapy to be effective. The present study aims to evaluate the extent to which CAR expression is observed in ILC in comparison to IDC, and how the levels of CAR expression correlate with adenovirus transduction efficiency. The effect of liposome encapsulation on transduction efficiency is also assessed.MethodsTo characterize CAR expression in invasive breast carcinoma, 36 formalin-fixed paraffin-embedded (FFPE) human breast tumor samples were assayed by CAR immunohistochemistry (IHC). Localization of CAR in comparison to other junctional proteins was performed using a multiplex immunofluorescence panel consisting of CAR, p120-catenin, and E-cadherin. ILC and IDC primary tumors and cell lines were transduced with E1- and E3-deleted adenovirus type 5 inserted with a GFP transgene (Ad-GFP) and DOTAP liposome encapsulated Ad-GFP (DfAd-GFP) at various multiplicities of infection (MOIs). Transduction efficiency was measured using a fluorescence plate reader. CAR expression in the human primary breast carcinomas and cell lines was also evaluated by IHC.ResultsWe observed membranous CAR, p120-catenin and E-cadherin expression in IDC. In ILC, we observed cytoplasmic expression of CAR and p120-catenin, with absent E-cadherin. Adenovirus effectively transduced high-CAR IDC cell lines, at MOIs as low as 12.5. Ad-GFP showed similar transduction as DfAd-GFP in high-CAR IDC cell lines. Conversely, Ad-GFP transduction of ILC cell lines was observed only at MOIs of 50 and 100. Furthermore, Ad-GFP did not transduce CAR-negative IDC cell lines even at MOIs greater than 100. Liposome encapsulation (DfAd-GFP) improved transduction efficiency 4-fold in ILC and 17-fold in CAR-negative IDC cell lines.ConclusionThe present study demonstrates that oncolytic adenoviral therapy is less effective in ILC than IDC due to differences in spatial CAR expression. Liposome-enhanced delivery may be beneficial for patients with ILC and tumors with low or negative CAR expression to improve adenoviral therapeutic effectiveness.

Genome editing tools, particularly the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) systems (e.g., CRISPR/Cas9), and their repurposing into epigenetic editing platforms, offer enormous potential as safe and customizable therapies for cancer. Specifically, various transcriptional abnormalities in human malignancies, such as silencing of tumor suppressors and ectopic re-expression of oncogenes, have been successfully targeted with virtually no off-target effects using CRISPR activation and repression systems. In these systems, the nuclease-deactivated Cas9 protein (dCas9) is fused to one or more domains inducing selective activation or repression of the targeted genes. Despite these advances, the efficient in vivo delivery of these molecules into the target cancer cells represents a critical barrier to accomplishing translation into a clinical therapy setting for cancer. Major obstacles include the large size of dCas9 fusion proteins, the necessity of multimodal delivery of protein and gRNAs, and the potential of these formulations to elicit detrimental immune responses.In this context, viral methods for delivering CRISPR face several limitations, such as the packaging capacity of the viral genome, the potential for integration of the nucleic acids into the host cells genome, and immunogenicity of viral proteins, posing serious safety concerns. The rapid development of mRNA vaccines in response to the COVID-19 pandemic has rekindled interest in mRNA-based approaches for CRISPR/dCas9 delivery. Simultaneously, due to their high loading capacity, scalability, customizable surface modification for cell targeting, and low immunogenicity, lipid nanoparticles (LNPs) have been widely explored as nonviral vectors. In this chapter, we first describe the design of optimized dCas9-effector mRNAs and gRNAs for epigenetic editing. We outline formulations of LNPs suitable for dCas9 mRNA delivery. Additionally, we provide a protocol for the co-encapsulation of the dCas9-effector mRNAs and gRNA into these LNPs, along with detailed methods for delivering these formulations to both cell lines (in vitro) and mouse models of breast cancer (in vivo).

Rationale: Microbubble (MB) contrast agents combined with ultrasound targeted microbubble cavitation (UTMC) are a promising platform for site-specific therapeutic oligonucleotide delivery. We investigated UTMC-mediated delivery of siRNA directed against epidermal growth factor receptor (EGFR), to squamous cell carcinoma (SCC) via a novel MB-liposome complex (LPX). Methods: LPXs were constructed by conjugation of cationic liposomes to the surface of C4F10 gas-filled lipid MBs using biotin/avidin chemistry, then loaded with siRNA via electrostatic interaction. Luciferase-expressing SCC-VII cells (SCC-VII-Luc) were cultured in Petri dishes. The Petri dishes were filled with media in which LPXs loaded with siRNA against firefly luciferase (Luc siRNA) were suspended. Ultrasound (US) (1 MHz, 100-µs pulse, 10% duty cycle) was delivered to the dishes for 10 sec at varying acoustic pressures and luciferase assay was performed 24 hr later. In vivo siRNA delivery was studied in SCC-VII tumor-bearing mice intravenously infused with a 0.5 mL saline suspension of EGFR siRNA LPX (7×108 LPX, ~30 µg siRNA) for 20 min during concurrent US (1 MHz, 0.5 MPa spatial peak temporal peak negative pressure, five 100-µs pulses every 1 ms; each pulse train repeated every 2 sec to allow reperfusion of LPX into the tumor). Mice were sacrificed 2 days post treatment and tumor EGFR expression was measured (Western blot). Other mice (n=23) received either EGFR siRNA-loaded LPX + UTMC or negative control (NC) siRNA-loaded LPX + UTMC on days 0 and 3, or no treatment (sham). Tumor volume was serially measured by high-resolution 3D US imaging. Results: Luc siRNA LPX + UTMC caused significant luciferase knockdown vs. no treatment control, p

In this study, multiple particle binding-liposomes (MPB-Lips), encapsulating the luminophore tris(2′,2-bipyridyl)ruthenium (II) complex ([Ru(bpy)3]2+), were developed as an electrochemiluminescence (ECL) signal amplifier and were applied to detect the model analyte streptavidin (SA) using the indirect competitive ECL method. The MPB-Lips were prepared by mixing various ratios of two different liposomes—one containing a phospholipid with a primary amine group and a biotinyl group (BIO/NH2-Lip) and one containing a phospholipid with an N-hydroxysuccinimide group (NHS-Lip) to allow binding between particles via amide bonds. Quartz crystal microbalance analysis using SA-modified gold-coated quartz crystals showed that the frequency shift values of MPB-Lips gradually decreased in the order BIO/NH2-Lip:NHS-Lip = 1:0 < 1:1 < 1:3 < 1:5. This indicated that MPB-Lips were successfully formed. The indirect competitive ECL method using SA-modified gold electrodes showed that the 1:5-Lip system had greater sensitivity than the 1:0-Lip system—the limit of detection and quantification values for the systems were 1.84 and 6.30 μg mL−1 for 1:0-Lip, and 1.20 and 1.74 μg mL−1 for 1:5-Lip. Finally, the recovery of SA spiked in fetal bovine serum samples using the 1:5-Lip system showed good accuracy and precision with a recovery rate of 83–106% and relative standard deviation of 4–14%. Our study demonstrated that the MPB-Lips system was an effective and useful ECL amplifier and the ECL method using MPB-Lips could be applied to detect an analyte in a real sample. [ABSTRACT FROM AUTHOR]

Background: Conventional therapies in cancer treatment face challenges including drug resistance, lack of specificity, and severe adverse reactions. This study explores the potential of liposomal transdermal delivery systems as an alternative to current therapies with improved BA and PK. The objective of the study was to formulate gefitinib liposomes by thin film hydration technique (TFH) using lipoid S100. A central composite design (CCD) was used to develop and optimize GEF-LIP-TDDs and to analyze the optimum concentrations of the selected variables (phospholipid, cholesterol) in liposomal formation. The model fitting was performed using Design-Expert (Stat-Ease, Ver 13). The GEF liposomes were evaluated for %EE, mean particle size and PDI. The optimized liposomes were fabricated as a transdermal patch by mercury substrate method and evaluated for %drug content, in vitro diffusion, in vivo biodistribution (PK and BA), and skin irritation studies in female Albino Wistar rats. The stability of the optimized transdermal patch was also assessed for 3 months. Results: The CCD model was significant with F-value of 37.97, P-value of 0.0500 and R2 of 0.9644. The average vesicle size, PDI, and ZP of GEF-LIPs (F1–F13) were found to be between 112.8 to 373.7 nm, 0.186 to 0.510 and − 3.69 to − 82.2 mV, respectively. F3-GEF-LIP exhibited a mean vesicle size of 96.07 nm, ZP of − 46.06 mV, and a PDI of 0.423. F3-GEF-LIP demonstrated exceptional %EE (97.79) and sustained release effect (%CDR, 83.32) following a diffusion-controlled mechanism. TEM images confirmed liposomes of multivesicular type (MVV, < 100 nm). Importantly, optimized F3-GEF-LIP-TD showed no signs of edema in Wistar rats. The biodistribution of F3-GEF-LIP-TD was similar to pure GEF and was higher in the liver (p < 0.05). The BA of F3-GEF-LIP-TD was observed to be 74.05 ± 0.11% in comparison with oral GEF-LIP (65.25 ± 0.08%) and pure GEF (58.10 ± 0.17%). Conclusion: TFH technique offers stable liposomes with high reproducibility. Our findings imply that GEF-LIP-TD provides enhanced BA and tissue distribution and can be considered as a substitution for orals or in combination for treating breast cancer. Lipoid S100 is a potential lipid for developing stable multivesicular nanoliposomes. [ABSTRACT FROM AUTHOR]

Melanoma is the most aggressive type of skin cancer, with few therapeutic alternatives following metastasis development. In recent years, drug delivery-associated nanotechnology has shown promising targeted results with diminished adverse effects compared to conventional treatments. This study aimed to (1) examine the effects of plant-derived α-arbutin, a natural compound and (2) compare these findings with bioactively developed liposomes containing α-arbutin utilizing the B16-F10 murine melanoma cell line as a model. Liposomes were obtained through reversed-phase evaporation by applying a spray dryer to assess their stability. The following biologic assays were measured cytotoxicity/antiproliferative (MTT, Neutral Red, and dsDNA PicoGreen). In addition, the levels of melanin and purinergic enzymes were also measured. The production of reactive oxygen species (ROS) and nitric oxide (NO) was determined as a measure of oxidative state. Treatment with nano-liposome containing alpha-arbutin induced a significant 68.4% cytotoxicity, similar to the positive control, in the B16-F10 murine melanoma cell line at 72 hr. Further, arbutin and liposomes containing alpha-arbutin increased levels of ROS and nitrite formation at 72 hr at the highest concentration (100 and 300 µg/ml) of treatments. Arbutin and liposomes containing alpha-arbutin reduced melanin levels at all tested concentrations. In addition, arbutin and alpha-arbutin containing liposomes lowered nucleotides (AMP, ADP, and ATP) and nucleoside (adenosine) levels in melanoma cells. Evidence suggests that α-arbutin containing liposome can be considered as an alternative immunosuppressive agent stimulated in melanoma treatment. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the applicability of Limulus amebocyte lysate (LAL) assay for endotoxin determination in lipid compounding liposomal nanoformulations. Materials & methods: Spiked cholesterol, hydrogenated soy phosphatidylcholine and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG 2000) samples with endotoxins, simulating contaminated samples or in-process contamination were analyzed by chromogenic LAL assay. Results: Recovery of spiked endotoxins was achieved from DSPE-PEG 2000 suspended in water, whereas recovery was not achieved from spiked cholesterol and hydrogenated soy phosphatidylcholine suspended in methanol, and from multilamellar vesicles. Conclusion: Endotoxins, when in contact with organic solvents, no longer react in the LAL assay as they do in aqueous media. This indicates limitations of the LAL assay for endotoxin control in raw materials for liposomal nanoformulations. Article highlights Lipid samples preparation for endotoxin determination Raw materials for liposome nanoformulations have low solubility in water. However, DSPE-PEG 2000 forms a homogeneous suspension in water, which does not interfere with the chromogenic Limulus amebocyte lysate (LAL) assay, according to the criteria established by several pharmacopeias (US, European and Japanese). Cholesterol (Chol) and hydrogenated soy phosphatidylcholine (HSPC) should be dissolved in organic solvents in order to determine the endotoxins eventually entrapped in them. Then, to mimic contaminated samples for interference testing, which are dissolved in MeOH for analysis by LAL assay, control standard endotoxin (CSE) resuspended in MeOH should be added. However, CSE resuspended in MeOH does not react in LAL assay as it does when resuspended in aqueous media. CSE reactivity in LAL assay under non-aqueous conditions When CSE comes into contact with organic solvents, it forms supramolecular structures that can influence its reactivity with the LAL reagent. Independent solutions of different concentrations do not react proportionally to the amounts of CSE, whereas solutions prepared by dilution from the highest concentrations do react proportionally. Therefore, if any sample is dissolved in organic solvents, as is the case with Chol and HSPC for the chromogenic LAL assay, the results cannot be relied upon for accurate endotoxin measurement. CSE resuspended in water is not affected by 2.5 and 5% MeOH. However, if C12E10 is added, the CSE no longer reacts proportionally in the LAL assay. Inhibition/enhancement controls of Chol and HSPC. Inhibition/enhancement controls should be carefully designed to mimic actual contaminated samples to ensure accurate measurement of endotoxins. These controls should also be conducted by spiking with different concentrations of endotoxins if they are assaying under non-aqueous matrices. Spiking LPS during the manufacturing of liposomes LPS was not detected in MLV prepared by spiking the lipid solution in EtOH but was detected in MLV prepared by spiking the aqueous solution (5% dextrose). The lipid medium affects endotoxin detection. Heating the spiked MLV samples at 75°C and 92°C for 30 min did not allow endotoxin detection. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effect of selected compounds from the group of triterpene sapogenins on model phosphatidylcholine membranes. Two types of biological membrane model systems were used in the work, i.e., liposomes (microelectrophoresis method) and spherical bilayers (interfacial tension method). Each model was modified with the tested sapogenin compounds, and the change in their physicochemical and electrical parameters was analyzed. Parameters characterizing the equilibrium in the membrane of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)-oleanolic acid (OA) and DPPC-asiatic acid (AA) were determined). Based on the Young-Laplace equation, the interfacial tensions of spherical lipid bilayers were measured. The formation of 1:1 complexes was assumed in the DPPC-OA and DPPC-AA membrane systems, and the parameters characterizing the interactions in the formed complexes were calculated. Microelectrophoresis was used to study the surface charge density of lipid membranes. These values were obtained from electrophoretic mobility data using Smoluchowsky's equation. The influence of pH on the electrolyte solution and the composition of the membranes was investigated. The results indicate that modifying DPPC membranes with selected triterpene sapogenins, both OA and AA, causes changes in the surface charge density and shifts of the isoelectric point. Data presented in this work, obtained through mathematical derivation and confirmed experimentally, are of great importance for interpreting phenomena occurring in lipid membranes. A quantitative description of equilibria between phosphatidylcholine and sapogenins lets us understand the processes on the membrane surface. The equilibria are particularly significant from the standpoint of cell functioning. Phosphatidylcholine-sapogenin interactions modulate a range of physicochemical properties of membranes, and they are important in the course of the multiple processes involving membranes in the living cell (e.g., transport mechanism). [ABSTRACT FROM AUTHOR]

This trial assessed the pharmacokinetics, pharmacodynamics, and safety of liposomal bupivacaine given via ultrasound‐guided popliteal sciatic nerve block with or without immediate‐release bupivacaine hydrochloride in adults having bunionectomies. Forty‐five adults were enrolled into four sequential cohorts: (1) liposomal bupivacaine 266 mg with bupivacaine hydrochloride 50 mg; (2) liposomal bupivacaine 133 mg with bupivacaine hydrochloride 50 mg; (3) liposomal bupivacaine 266 mg; or (4) bupivacaine hydrochloride 100 mg. Outcomes included pharmacokinetics (e.g., bupivacaine maximum plasma concentration [Cmax]), onset and duration of motor and sensory nerve block, and safety. Liposomal bupivacaine admixed with bupivacaine hydrochloride produced biphasic bupivacaine plasma disposition profiles with two distinct peaks. Geometric mean Cmax of the early peak ranged from 235 to 421 ng/mL and the geometric mean of the late Cmax was ∼30%–50% lower than the early peak. Median time to sensory block onset was 18 to 29 min in all cohorts. Sensory blocks lasted about twice as long with liposomal bupivacaine (median, 119–167 h) than with bupivacaine hydrochloride alone (median, 67 h). There were no serious adverse events. In conclusion, liposomal bupivacaine provided prolonged sensory nerve block when given as popliteal sciatic nerve blocks with or without bupivacaine hydrochloride, and bupivacaine plasma concentrations were well below the lower bound of the toxicity threshold of 2000 ng/mL for all cohorts. [ABSTRACT FROM AUTHOR]

Organoids are "mini-organs" that self-organize and differentiate from stem cells under in vitro 3D culture conditions, mimicking the spatial structure and function of tissues in vivo. Extracellular vesicles (EVs) are nanoscale phospholipid bilayer vesicles secreted by living cells, rich in bioactive molecules, with excellent biocompatibility and low immunogenicity. Compared to EVs, organoid-derived EVs (OEVs) exhibit higher yield and enhanced biological functions. Organoids possess stem cell characteristics, and OEVs are capable of delivering active substances, making both highly promising for medical applications. In this review, we provide an overview of the fundamental biological principles of organoids and OEVs, and discuss their current applications in disease treatment. We then focus on the differences between OEVs and traditional EVs. Subsequently, we present methods for the engineering modification of OEVs. Finally, we critically summarize the advantages and challenges of organoids and OEVs. In conclusion, we believe that a deeper understanding of organoids and OEVs will provide innovative solutions to complex diseases. [ABSTRACT FROM AUTHOR]

Advancing therapeutic progress is centered on developing drug delivery systems (DDS) that control therapeutic molecule release, ensuring precise targeting and optimal concentrations. Targeted DDS enhances treatment efficacy and minimizes off‐target effects, but struggles with drug degradation. Over the last three decades, nanopharmaceuticals have evolved from laboratory concepts into clinical products, highlighting the profound impact of nanotechnology in medicine. Despite advancements, the effective delivery of therapeutics remains challenging because of biological barriers. Nanocarriers offer a solution with a small size, high surface‐to‐volume ratios, and customizable properties. These systems address physiological and biological challenges, such as shear stress, protein adsorption, and quick clearance. They allow targeted delivery to specific tissues, improve treatment outcomes, and reduce adverse effects. Nanocarriers exhibit controlled release, decreased degradation, and enhanced efficacy. Their size facilitates cell membrane penetration and intracellular delivery. Surface modifications increase affinity for specific cell types, allowing precise treatment delivery. This study also elucidates the potential integration of artificial intelligence with nanoscience to innovate future nanocarrier systems. [ABSTRACT FROM AUTHOR]

Berberine hydrochloride (BH) extracted from Coptis chinensis (CC) and Matrine (MT) separated from Sophora flavescens (SF) are alkaloids with potent anti-bacterial, anti-inflammatory, and anti-tumor effects. Motivated by the clinical practice of using CC and SF together, we aimed to demonstrate that the synergistic application of the natural compounds BH and MT could enhance therapeutic effects and minimize side effects. Two types of liposomes, liposomes containing only BH (BH-LP) and liposomes containing both BH and MT (BH-MT-LP), were successfully prepared via the reverse evaporation method. The liposome preparation process was optimized by single-factor screening and the Box–Behnken experimental design method. The results showed that the liposomes had particle sizes in the range of 222.7 to 235.4 nm, polydispersity indicated in the range of 11.8% to 23.3%, and zeta potentials in the range of −35.9 to −31.1 mv. BH-MT-LP showed superior anti-tumor activity against MDA-MB-231, HepG-2, and HGC-27 cells in vitro. The incorporation of MT effectively promoted the anti-tumor effect of BH, while the controlled release from liposomes further enhanced the therapeutic efficacy of BH. Furthermore, based on the flow cytometry results, we speculated that BH-MT-LP might promote apoptosis by blocking the G1 phase of cells and inducing cell death. In conclusion, BH-MT-LP provides evidence for the combined use of natural compounds as a stable, safe, and practical drug delivery system for the treatment of potential cancers. Meanwhile, the successful preparation for BH-MT-LP also provides a new approach to the combined use of traditional Chinese medicine ingredients. [ABSTRACT FROM AUTHOR]

Understanding carboxylate transport through lipid membranes under physiological conditions is critical in biomedicine and biotechnology, as it allows for the emulation of biological membrane functions and can enhance the absorption of hydrophobic carboxylate-based drugs. However, the structural diversity of carboxylates has made it challenging to study their transport, and the limited available examples do not provide a comprehensive understanding of the role of the organic moiety in this process. Here, we present an in-depth analysis of the diffusion and transport of various aliphatic and aromatic carboxylates into liposomes. We assessed the influence of their size, number of carboxylate groups, and presence of hydroxyl groups. Our findings from fluorescence assays, using lucigenin and HPTS as probes, revealed that most carboxylates can spontaneously diffuse into liposomes in their protonated state, facilitated by the efflux of HNO3 when using NaNO3 solutions at pH 7. The Cl-ISE assay showed chloride/carboxylate exchange by a synthetic anion transporter. Clear trends were observed when the organic moiety was systematically varied, with a particular enhancement of anion transport by the presence of hydroxyl groups in the aromatic carboxylates. Our findings provide insights into the processes by which carboxylates can enter liposomes, which can contribute to understanding the transport of other biologically relevant organic anions. [ABSTRACT FROM AUTHOR]

Psoriasis and breast cancer are two examples of diseases where associated inflammatory pathways within the body's immune system are implicated. Psoriasis is a complex, chronic and incurable inflammatory skin disorder that is primarily recognized by thick, scaly plaques on the skin. The most noticeable pathophysiological effect of psoriasis is the abnormal proliferation of keratinocytes. Breast cancer is currently the most diagnosed cancer and the leading cause of cancer-related death among women globally. While treatments targeting the primary tumor have significantly improved, preventing metastasis with systemic treatments is less effective. Nanocarriers such as liposomes and lipid nanoparticles have emerged as promising drug delivery systems for drug targeting and specificity. Advances in technologies and drug combinations have emerged to develop more efficient lipid nanocarriers to include more than one drug in combinational therapy to enhance treatment outcomes and/or relief symptoms for better patients' quality of life. Although there are FDA-approved liposomes with anti-cancer drugs for breast cancer, there are still unmet clinical needs to reduce the side effects associated with those nanomedicines. Hence, combinational nano-therapy may eliminate some of the issues and challenges. Furthermore, there are no nanomedicines yet clinically available for psoriasis. Hence, this review will focus on liposomes encapsulated single and/or combinational therapy to augment treatment outcomes with an emphasis on the effectiveness of combinational therapy within liposomal-based nanoparticulate drug delivery systems to tackle psoriasis and breast cancer. This review will also include an overview of both diseases, challenges in delivering drug therapy and the roles of nanomedicines as well as psoriasis and breast cancer models used for testing therapeutic interventions to pave the way for effective in vivo testing prior to the clinical trials. [ABSTRACT FROM AUTHOR]

Simple Summary: STING agonists face challenges in breast cancer treatment due to their lower accumulation in tumors and rapid clearance from the body, resulting in a short duration of therapeutic effect. Novel phase-transitional liposomes loaded with STING agonists have been developed to overcome these limitations and are specifically designed for low-intensity focused ultrasound (LIFU)-assisted molecular imaging and precise treatment of breast cancer. With the assistance of LIFU, iRGD-modified liposomes (a targeting peptide) undergo a phase transition into microbubbles, leading to enhanced ultrasound molecular imaging of tumors and facilitating breast cancer immunotherapy by releasing STING agonists from the ultrasound-targeted liposomes. Background: Pharmacologically targeting the STING pathway offers a novel approach to cancer immunotherapy. However, small-molecule STING agonists face challenges such as poor tumor accumulation, rapid clearance, and short-lived effects within the tumor microenvironment, thus limiting their therapeutic potential. To address the challenges of poor specificity and inadequate targeting of STING in breast cancer treatment, herein, we report the design and development of a targeted liposomal delivery system modified with the tumor-targeting peptide iRGD (iRGD-STING-PFP@liposomes). With LIFU irradiation, the liposomal system exploits acoustic cavitation, where gas nuclei form and collapse within the hydrophobic region of the liposome lipid bilayer (transient pore formation), which leads to significantly enhanced drug release. Methods: Transmission electron microscopy (TEM) was used to investigate the physicochemical properties of the targeted liposomes. Encapsulation efficiency and in vitro release were assessed using the dialysis bag method, while the effects of iRGD on liposome targeting were evaluated through laser confocal microscopy. The CCK-8 assay was used to investigate the toxicity and cell growth effects of this system on 4T1 breast cancer cells and HUVEC vascular endothelial cells. A subcutaneous breast cancer tumor model was established to evaluate the tumor-killing effects and therapeutic mechanism of the newly developed liposomes. Results: The liposome carrier exhibited a regular morphology, with a particle size of 232.16 ± 19.82 nm, as indicated by dynamic light scattering (DLS), and demonstrated low toxicity to both HUVEC and 4T1 cells. With an encapsulation efficiency of 41.82 ± 5.67%, the carrier exhibited a slow release pattern in vitro after STING loading. Targeting results indicated that iRGD modification enhanced the system's ability to target 4T1 cells. The iRGD-STING-PFP@liposomes group demonstrated significant tumor growth inhibition in the subcutaneous breast cancer mouse model with effective activation of the immune system, resulting in the highest populations of matured dendritic cells (71.2 ± 5.4%), increased presentation of tumor-related antigens, promoted CD8+ T cell infiltration at the tumor site, and enhanced NK cell activity. Conclusions: The iRGD-STING-PFP@liposomes targeted drug delivery system effectively targets breast cancer cells, providing a new strategy for breast cancer immunotherapy. These findings indicate that iRGD-STING-PFP@liposomes could successfully deliver STING agonists to tumor tissue, trigger the innate immune response, and may serve as a potential platform for targeted immunotherapy. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine (1) the dose of liposomal bupivacaine (LB) to eliminate grade 2 of 5 lameness, the (2) duration of analgesia of LB versus bupivacaine hydrochloride (BH), and (3) LB pharmacokinetics versus BH. METHODS: A reversible lameness model was validated in conditioned Thoroughbred horses (n = 12), aged 3 to 10 years. A dose-response trial compared subjective and objective lameness following abaxial sesamoid block with 25 mg BH/nerve or 30, 60, or 133 mg LB/nerve (n = 3/group). The LB dose that eliminated lameness and reduced lameness for the longest was used for blinded, randomized, crossover pharmacokinetic/pharmacodynamic trials (n = 12/group). Data were analyzed using a paired t test or Wilcoxon signed-rank test, P < .05. RESULTS: The 133-mg/nerve dose of LB eliminated lameness in 3 of 3 horses in the dose-response trial, and lameness returned at 6, 36, and 72 hours. In the pharmacokinetic/pharmacodynamic trials, time to return of lameness greater than or equal to starting lameness was longer for LB compared to BH on subjective (LB, 12 hours, 4 to 24 hours; BH, 4 hours, 4 to 12 hours) and objective (LB, 12 hours, 4 to 24 hours; BH, 4 hours, 2 to 6 hours) evaluations. The terminal halflife was not different between formulations (LB, 17.8 hours ± 10.1; BH, 12.4 hours ± 6.3); however, LB had increased area under the concentration-versus-time curve from time 0 to infinity (LB, 388 ng·h/mL ± 117; BH, 63 ng·h/mL ± 18) and mean residence time (LB, 17.6 hours ± 2.4; BH, 3.9 hours ± 1.6). CONCLUSIONS: Liposomal bupivacaine analgesia duration was greater than BH, but the median time until lameness returned was only 12 hours. Bupivacaine is quantifiable in serum and urine beyond loss of clinical effect. CLINICAL RELEVANCE: A single, high-dose injection of LB is not effective for providing perineural analgesia over several days. Bupivacaine is detectable after the effect of the drug has worn off. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a global health concern with high prevalence and mortality. A marine alkaloid, AP‐427, has been reported to show potential for HCC treatment. However, its use is limited by low solubility and high toxicity. We aimed to investigate the preformulation parameters and develop AP‐427 liposomes to improve its clinical suitability. A stability‐indicating HPLC assay was established, and the physicochemical properties of AP‐427 were analyzed. Afterward, AP‐427 liposomes were prepared and characterized, and their cytotoxicity was evaluated. AP‐427 had a low solubility at physiological pH, a LogD of 2.56 ± 0.03, and a basic pKa of 3.24 ± 0.12. An entrapment efficiency of 52.71 ± 3.2% was achieved after optimization. The resulting AP‐427 liposomes were 147.2 ± 3.4 nm and stable up to three months when stored in a pellet form at 4°C. The crystallization of AP‐427 in liposomes became less ordered, and AP‐427 liposomes exhibited a controlled release fitted in Korsmeyer–Peppas model, indicating the release was driven by diffusion. Furthermore, AP‐427 liposomes showed a 3.6 times reduced cytotoxicity against HepG2 cells compared with free AP‐427, potentially enhancing its antitumor efficacy. In conclusion, the precise preformulation parameters advanced the AP‐427 liposomal formulation development, which showed potential for HCC treatment. Practical Applications: The aaptamine derivative AP‐427 has shown cytotoxic effects against hepatocellular carcinoma. However, the low solubility and high toxicity limit its clinical application. The present study aims to prepare liposomal formulation to solve the current problems. Results obtained from this study shed light on challenges related to drug solubility and have paved the way for the development of an effective AP‐427 liposomal formulation with promising application in hepatocellular carcinoma therapy. [ABSTRACT FROM AUTHOR]

This study delves into the optimization of niosomal production for biological applications, focusing on their emerging role as amphiphilic nanoparticles derived from nonionic surfactants, poised at the forefront of biomedical research. We aimed to formulate and characterize a diverse array of niosomal nanoparticles, with particular emphasis on process‐related parameters and physicochemical characteristics. Critical thresholds for size, polydispersity, and zeta potential were established to identify parameters crucial for optimal niosomal formulations through a comprehensive investigation of concentrations, sonication times, ingredient ratios, and surfactant types. Leveraging MODDE software, we generated 10 optimized formulations from preliminary parameter screening. The proposed experimental model design by the software exhibited acceptable similarity to the obtained experimental results (F‐score: 0.83). The criteria for selection of the predicted experimental model formed based on targeted physicochemical considerations. To enhance half‐life and penetration, especially in higher electrostatic regions like the central nervous system (CNS), we proposed a neutralized surface charge (−10 to 10 mV) while maintaining size within 100–200 nm and polydispersity below 0.5. Extended stability screening revealed periodic and extended Gaussian distributions for size and zeta potential to minimize flocculation and coagulation caused by neutralized surface charge. Notably, the cellular response performance of optimized niosomes was assessed via cellular binding, uptake, and viability in comparison with liposomes. Glioblastoma cell line (U‐87) and granulocyte colony‐stimulating factor (G‐CSF) containing lymphoblastic leukemia cell line (NFS‐60) were chosen to represent tumors developed in the CNS region and white blood cells, respectively, enabling a comprehensive comparative analysis with liposomes. The meticulous comparison between niosomes and liposomes revealed comparable cellular viability profiles on both U‐87 and NFS‐60 cell lines, highlighting their similarities in cellular interactions. Moreover, selected niosomal formulations demonstrated exceptional cellular uptake, either equaling or surpassing observed liposomal uptake. One of the most promising niosomes was selected and optimized to evaluate drug encapsulation performance of niosomes for further drug delivery adaptations by one of the chemotherapy drugs, paclitaxel (PTX). Cytotoxicity study was established with the most efficiently encapsulated niosomal condition with human‐derived fibroblasts (HDFs) and U‐87 as the representation of healthy and cancerous cell lines. Results demonstrated 1:100 diluted PTX‐loaded niosome in the certain concentration demonstrated favorable toxicity in U‐87 than original PTX at the same concentration while not disturbing healthy HDFs. These findings underscore the potential of niosomes for reliable drug delivery, challenging the dominance of liposomal vehicles and presenting economically viable nanocarriers with significant implications for advancing biomedical research. [ABSTRACT FROM AUTHOR]

From targeted gene insertion techniques to gene editing tool delivery systems, nanotechnology presents a promising path for improving many aspects of crop modification. However, little is known about the current application of nanotechnology and genetic engineering (GE) to improve agricultural yield. This review explores the potential applications of nanotechnology and GE to enhance sustainable agricultural systems. Most of the research indicates that by carefully guiding the delivery of nutrients to plants, nanomaterials and nanoscale methods like nanofertilizers and nanocarriers maximize plant nutrient uptake efficiency and increase the efficacy of agriculture's utilization of resources. Studies reveal that the application of nanoencapsulated pesticides as well as antimicrobial agents ensures precise delivery to plant tissues, maximizing effectiveness and reducing chemical usage. Nanotechnology also offers more precise control over genetic modifications and produces crops with desired traits like enhanced nutrient content, boosted resistance to pests and diseases, and raised yield. This fusion of GE and nanotechnology is an example of a modern approach to sustainable agriculture that maximizes resource use while reducing environmental impact. This review clarifies the promise of nanotechnology as a clean technology for transforming the production of genetically modified crops, improving nutrient utilization, and thus contributing to worldwide food security and environmentally-friendly agriculture. [ABSTRACT FROM AUTHOR]

Cancer therapeutic resistance as a common hallmark of cancer is often responsible for treatment failure and poor patient survival. Cancer stem-like cells (CSCs) are one of the main contributors to therapeutic resistance, cancer relapse and metastasis. Through screening from our in-house library of natural products, we found polyphyllin II (PPII) as a potent anti-CSC compound for triple-negative breast cancer (TNBC). To enhance anti-CSC selectivity and improve druggability of PPII, we leverage the liposome-mediated delivery technique for increasing solubility of PPII, and more significantly, attaining broader therapeutic window. Liposomal PPII demonstrates its marked potency to inhibit tumor growth, post-surgical recurrence and metastasis compared to commercial liposomal chemotherapeutics in the mouse models of CSC-enriched TNBC tumor. We further identify PPII as an inhibitor of the Ras-related nuclear (RAN) protein whose upregulated expression is correlated with poor clinical outcomes. The direct binding of PPII to RAN reduces TNBC stemness, thereby suppressing tumor progression. Our work offers a significance from drug discovery to drug delivery benefiting from liposome technique for targeted treatment of high-stemness tumor. [Display omitted] • PPII, a natural product, effectively eliminates CSC-like cell population. • Liposome delivery enhances anticancer selectivity and efficacy of PPII. • RAN is identified as novel target of PPII. • PPII binds RAN to reduce tumor stemness phenotype. [ABSTRACT FROM AUTHOR]

Summary: Encapsulation efficiency (EE), structure, antioxidant and antimicrobial activities of liposomes loaded with chitooligosaccharide–gallic acid conjugate (COS–GAL) as affected by cholesterol (CHO) and ascorbyl palmitate (AP) as stabilisers were investigated. In addition, release kinetics and in vitro digestion of selected liposomes were also studied. The higher EE was obtained for liposome (AP/COS–GAL) stabilised by 0.50% AP, when used to encapsulate 0.10% COS–GAL conjugate. The highest EE was noticed for 0.25% CHO when used to encapsulate 1.00% conjugate (CHO/COS–GAL) as compared to the counterparts (P < 0.05). Almost similar antioxidant and antimicrobial activities were noticed for all COS–GAL liposomes and COS–GAL powder. Microstructure study suggested the formation of bilayer in liposomes. CHO/COS–GAL showed a lower release efficiency than the AP/COS–GAL. CHO/COS–GAL was also able to protect conjugate during the in vitro digestion. Therefore, liposomes could be used as a promising carrier of COS–GAL conjugate in both foods as well as medical systems. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) and ferroptosis therapy have received extensive attention in breast cancer treatment. PDT induced apoptosis of tumor cells by producing a large amount of reactive oxygen species (ROS) under laser irradiation. Differently, ferroptosis therapy exerts its antitumor effect by inducing excessive accumulation of lipid peroxides on tumor cell membranes. Based on that, ROS produced by PDT may promote ferroptosis in tumor cells, and ferroptosis therapy is expected eliminate apoptosis-resistant tumor cells. Therefore, a synergistic ferroptosis-photodynamic therapy will be more effective and more potential in breast cancer treatment. Considering PDT has the characteristic of producing ROS, and neutrophil has a natural tendency to ROS, a neutrophil-mimetic hybrid liposome (CR-NML) was designed for co-delivery of the photosensitizer Ce6 and the ferroptosis inducer RSL3. CR-NML targeted tumor through the ROS tendency of neutrophil and the enhanced permeability and retention (EPR) effect of liposome, then induced both apoptosis and ferroptosis in tumor cells, which increased ROS level and finally realized ROS cascade amplification. The synergistic ferroptosis-photodynamic therapy demonstrated significant therapeutic efficacy in 4T1 tumor bearing mice, which provided a promising strategy for breast cancer treatment. [ABSTRACT FROM AUTHOR]

Purpose: Quantitative magnetization transfer (qMT) models aim to quantify the contributions of lipids and macromolecules to the MRI signal. Hence, a model system that relates qMT parameters and their molecular sources may improve the interpretation of the qMT parameters. Here we used membrane lipid phantoms as a meaningful tool to study qMT models. By controlling the fraction and type of membrane lipids, we could test the accuracy, reliability, and interpretability of different qMT models. Methods: We formulated liposomes with various lipid types and water‐to‐lipids fractions and measured their signals with spoiled gradient‐echo MT. We fitted three known qMT models and estimated six parameters for every model. We tested the accuracy and reproducibility of the models and compared the dependency among the qMT parameters. We compared the samples' qMT parameters with their water‐to‐lipid fractions and with a simple MTnorm (= MTon/MToff) calculation. Results: We found that the three qMT models fit the membrane lipids signals well. We also found that the estimated qMT parameters are highly interdependent. Interestingly, the estimated qMT parameters are a function of the membrane lipid type and also highly related to the water‐to‐lipid fraction. Finally, we find that most of the lipid sample's information can be captured using the common and easy to estimate MTnorm analysis. Conclusion: qMT parameters are sensitive to both the water‐to‐lipid fraction and to the lipid type. Estimating the water‐to‐lipid fraction can improve the characterization of membrane lipids' contributions to qMT parameters. Similar characterizations can be obtained using the MTnorm analysis. [ABSTRACT FROM AUTHOR]

Liposomes being a promising colloidal system facilitates delivery of drugs with limited pharmacokinetic properties to achieve desirable clinical applications. However, development of a stable liposomal system is always challenging due to multiple complexities involved. Aqueous instability of liposomes and impact of various process and formulation parameters can lead to serious alteration of its therapeutic performance. In the proposed work, the authors aim to develop stable Ibrutinib-loaded liposomes using lyophilization and Quality-by-Design and assess their long-term stability. Ibrutinib-loaded liposomes were developed and optimized using Quality-by-Design technique and were further PEGylated and characterized for the same. Effect of cryoprotectants during lyophilization and other parameters are evaluated to obtain a robust formulation. The stability studies were conducted upto 6 months at various storage conditions to evaluate the effect of lyophilization. The impact of formulation, processing and lyophilization parameters on physicochemical properties of developed liposomal systems were evaluated and are critically discussed. Liquid dispersion exhibited a %degradation of 16–36% at 25 °C/60% RH which was reduced for less than 1% in lyophilized formulation for 6 months. Critical analysis and assessment of various parameters lead to identification of optimum conditions to manufacture this drug product and also opens way forward for further evaluation and translational possibilities. [ABSTRACT FROM AUTHOR]

In this study, the interaction of antimicrobial peptide Maximin 3 (Max3) with three different lipid bilayer models was investigated to gain insight into its mechanism of action and membrane specificity. Bilayer perturbation assays using liposome calcein leakage dose–response curves revealed that Max3 is a selective membrane‐active peptide. Dynamic light scattering recordings suggest that the peptide incorporates into the liposomal structure without producing a detergent effect. Langmuir monolayer compression assays confirmed the membrane inserting capacity of the peptide. Attenuated total reflection‐Fourier transform infrared spectroscopy showed that the fingerprint signals of lipid phospholipid hydrophilic head groups and hydrophobic acyl chains are altered due to Max3‐membrane interaction. On the other hand, all‐atom molecular dynamics simulations (MDS) of the initial interaction with the membrane surface corroborated peptide‐membrane selectivity. Peptide transmembrane MDS shed light on how the peptide differentially modifies lipid bilayer properties. Molecular mechanics Poisson–Boltzmann surface area calculations revealed a specific electrostatic interaction fingerprint of the peptide for each membrane model with which they were tested. The data generated from the in silico approach could account for some of the differences observed experimentally in the activity and selectivity of Max3. [ABSTRACT FROM AUTHOR]

In recent decades, nanotechnology has significantly advanced drug delivery systems, particularly in targeting subcellular organelles, thus opening new avenues for disease treatment. Mitochondria, critical for cellular energy and health, when dysfunctional, contribute to cancer, neurodegenerative diseases, and metabolic disorders. This has propelled the development of nanomedicines aimed at precise mitochondrial targeting to modulate their function, marking a research hotspot. This review delves into the recent advancements in mitochondrial-targeted nanotherapeutics, with a comprehensive focus on targeting strategies, nanocarrier designs, and their therapeutic applications. It emphasizes nanotechnology’s role in enhancing drug delivery by overcoming biological barriers and optimizing drug design for specific mitochondrial targeting. Strategies exploiting mitochondrial membrane potential differences and specific targeting ligands improve the delivery and mitochondrial accumulation of nanomedicines. The use of diverse nanocarriers, including liposomes, polymer nanoparticles, and inorganic nanoparticles, tailored for effective mitochondrial targeting, shows promise in anti-tumor and neurodegenerative treatments. The review addresses the challenges and future directions in mitochondrial targeting nanotherapy, highlighting the need for precision, reduced toxicity, and clinical validation. Mitochondrial targeting nanotherapy stands at the forefront of therapeutic strategies, offering innovative treatment perspectives. Ongoing innovation and research are crucial for developing more precise and effective treatment modalities. [ABSTRACT FROM AUTHOR]

AbstractGiant liposomes, or giant unilamellar vesicles (GUVs), have been utilized as cell-size bioreactors to replicate the physical and chemical properties of biological cells. However, conventional methods for preparing GUVs typically lack precise control over their size. Several research groups have recently developed microfluidic techniques to create monodisperse GUVs by generating water-in-oil-in-water (W/O/W) droplets with a thin oil layer that subsequently transform into GUVs. However, the formation of a thin oil shell requires the intricate control of the flow rate, which can be both challenging and unstable. In this study, we investigated the design of a two-step flow-focusing microfluidic channel to produce stable W/O/W droplets. These droplets underwent substantial oil layer reduction through spontaneous removal by fluidic shear forces. Consequently, the majority of the oil layer in the W/O/W droplets was reduced, improving uniformity of GUVs. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a neuroimmunological disorder which causes axonal damage, demyelination and paralysis. Although numerous therapeutics have been developed for the effective treatment of MS and a few have been approved in recent decades, complete remission and treatment of MS remain a matter of concern. Nanotechnology is a potential approach for manipulating the properties of materials at the molecular level to attain desired properties. This approach is effective in the treatment of several CNS disorders by enhancing drug delivery, bioavailability and efficacy. We have briefly discussed the neuroimmunological disorders with a particular emphasis on MS. We also explored nanoengineered drug delivery systems, describing several nano-formulations for the treatment of MS, challenges and future of nanotechnology. [ABSTRACT FROM AUTHOR]

ABSTRACT Nonmelanoma skin cancer (NMSC) represents the most prevalent form of skin cancer globally, with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) being the most common types. The search for effective chemopreventive and therapeutic agents has led to the exploration of natural compounds, among which resveratrol (RES), a polyphenolic phytoalexin found in grapes, berries, peanuts, and red wine, has garnered significant attention. This comprehensive review aims to elucidate the effects of RES on NMSC, focusing on its mechanisms of action, efficacy in preclinical studies, and potential as a chemopreventive and therapeutic agent. RES exhibits promising chemopreventive and antineoplastic capabilities against NMSC through various mechanisms, including the induction of apoptosis, inhibition of cell proliferation, modulation of oxidative stress, and anti‐inflammatory activities. Studies have demonstrated that RES can significantly enhance the effectiveness of traditional chemotherapeutic agents, such as 5‐fluorouracil (5‐FU), by inhibiting cellular proliferation and inducing apoptosis in cancerous cells. Furthermore, resveratrol's antioxidant properties may mitigate the impact of reactive oxygen species (ROS) triggered by UV exposure, thus reducing DNA damage and mutations associated with skin cancer development. In vitro and in vivo experiments have shown that RES can effectively hinder the growth and spread of various tumor cell types, including human cutaneous SCC A431 cells, and induce apoptosis. The development of advanced delivery systems, such as nanostructured lipid carriers and liposomes, has been recognized for their potential to enhance the therapeutic effects of RES, particularly its anticancer properties. In conclusion, RES presents a viable candidate for the prevention and treatment of NMSC, owing to its multifaceted mechanisms of action, including its ability to regulate oxidative stress, trigger apoptosis, and inhibit proliferation. However, further clinical studies are required to fully understand its effectiveness and safety in humans, as well as to optimize delivery methods for improved bioavailability and therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Cell membrane nanoparticles have attracted increasing interest in nanomedicine because they allow to exploit the complexity of cell membrane interactions for drug delivery. Several methods are used to obtain plasma membrane to generate cell membrane nanoparticles. Here, an optimized method combining nitrogen cavitation in isotonic buffer and sucrose gradient fractionation is presented. The method allows to obtain cell membrane fractions of high purity from both suspension and adherent cells. Comparison with other common methods for membrane extraction, where mechanical lysis using cell homogenizers is performed in isotonic or hypotonic buffers, shows that the optimized procedure yields high purity membrane in a robust and reproducible way. Procedures to mix the purified membrane with synthetic lipids to obtain cell membrane liposomes (CMLs) are presented and indications on how to optimize these steps are provided. CMLs made using crude membrane isolates or the purified membrane fractions show different uptake by cells. The CMLs made with the optimized procedure and liposomes of the same composition but without cell membrane components are thoroughly characterized and compared for their size, zeta potential, bilayer and mechanical properties to confirm membrane protein inclusion in the CMLs. Cell uptake studies confirm that the inclusion of membrane components modifies liposome interactions with cells. [ABSTRACT FROM AUTHOR]

This study demonstrates the feasibility of extracting lecithin from oil industry byproducts in an eco‐friendly manner, with minimal use of water and without harmful chemicals. Liposomes can be generated directly from this extracted lecithin, enhancing the value of these byproducts and enabling the production of catalytic gold nanoparticles (AuNPs). Thin‐layer chromatography of the extracted lecithin revealed a phospholipid composition primarily consisting of phosphatidylethanolamine and phosphatidylcholine, and surface tension studies demonstrated similar behavior between the extracted and commercial lecithin. Liposome formation using sustainable lecithin (LPn) resulted in structures that were stable for at least 10 days, exhibiting a low polydispersity index (0.395) and uniform size (approximately 214 ± 7 nm). Gold nanoparticles were synthesized successfully in LPn loaded with [HAuCl4] by using different photoreduction methods: ultraviolet (UV) lamp, pulsed laser 355 nm, and sunlight irradiation. The AuNPs exhibited characteristic sizes (ranging from 5.03 to 6.78 nm) and optical properties typical of nanoparticles, including a distinct surface plasmon resonance. As a proof of concept, we also demonstrated that the synthesized AuNPs exhibited catalytic activity in UV‐induced cis‐trans isomerization reactions. Overall, the study highlights the potential of sustainable soy lecithin extraction for diverse applications, including nanoparticle synthesis and catalysis. [ABSTRACT FROM AUTHOR]

Polysaccharides are an attractive source for use in dressings due to their plentiful availability, low cost, biodegradability, biocompatibility and multifunctionality. In this work, we describe the preparation, characterization and evaluation of the healing capacity of chitosan films produced via the solvent evaporation method containing β- D -glucan obtained from Rhodotorula mucilaginosa yeast and bromelain extracted from pineapple (Ananas comosus), in free form or incorporated in liposomes or associated with polymeric nanoparticles. The films were characterized according to the swelling degree, thermal stability and enzymatic activity, and in vivo tests were performed to evaluate the films' healing potential. The swelling degree of films with bioactive substances ranged from 110.69% to 185.82%, indicating that the films are suitable for use on non-exudative wounds. The films, when stored in a refrigerator, remained functional and maintained enzymatic activity for up to 30 days. Histopathological results showed the absence of edema, a low amount of inflammatory infiltrate and an increase in angiogenesis during the proliferative phase, with such events possibly involving the action of active compounds in films. The results showed promise for wound healing (wound contraction of 76.37%) using films containing bromelain and beta glucan for seven days. [ABSTRACT FROM AUTHOR]

The use of proteins as targeting agents often requires their chemical modification for their efficient attachment to a given surface. However, no control over the protein integrity and functionality has been demonstrated to date. Chemical over‐modification causes the loss of the native structure of the protein and thus limits its targeting efficiency. To preserve structural integrity, a minimal modification strategy of proteins is developed while maintaining their functionality. Apolipoprotein A1 (ApoA1) and liposomes are utilized as a nanocarrier platform. Monitoring NHS ester chemistry by time‐of‐flight mass spectrometry experiments, the proposed functionalization route allows the effective chemical coupling of the minimally modified ApoA1 to the surface of the liposomes via a click chemistry reaction. The stability of the modified ApoA1 is ensured by analyzing the secondary structure by circular dichroism spectroscopy and the corresponding melting point by nano differential scanning fluorimetry. Furthermore, ApoA1 attachment to the liposomes is confirmed by flow cytometry experiments. The procedure presented in this study has the potential to be easily transferred to other proteins while introducing only minimally necessary chemical modifications to be covalently attached to different drug delivery platforms. This can help to improve their targeting efficiency for future biomedical applications. [ABSTRACT FROM AUTHOR]

Treatment for Parkinson's disease (PD) has been impeded by inefficient treatment results and multiple membrane barriers during drug delivery. This study reports the design, synthesis, and application of microneedles (MNs) loaded with mitochondrion-targeted liposome encapsulated iron (Fe)-isolated single-atom nanozymes (Mito@Fe-ISAzyme, MFeI), called MFeI MNs, for in situ drug delivery into the brain parenchyma and efficient enrichment of drugs in lesion sites. In in vitro experiments, MFeI can scavenge reactive oxygen species (ROS) and protect the neurons via mitochondrial targeting, guaranteeing the subsequent treatment of PD. Using PD mouse models, we compared the intravenous injection of MFeI with the brain in situ administration of MFeI MNs (in situ MFeI MNs). Results showed that in situ MFeI MNs significantly improved the deep penetration of the drug into brain parenchyma, especially in the vital pathological sites such as the substantia nigra pars compacta and striatum. Importantly, ROS elimination and neuroinflammatory remission in the lesion site were observed, thereby efficiently alleviating the behavioral disorders and pathological symptoms of PD mice. Therefore, the MNs system for in situ single-atom nanozyme liposome delivery exhibits great potential in PD treatment. [ABSTRACT FROM AUTHOR]

Gold nanoparticles (AuNPs) are potentially applicable in drug/nucleic acid delivery systems. Low toxicity, high stability, and bioavailability are crucial for the therapeutic use of AuNPs and they are mainly determined by their interactions with proteins and lipids on their route to the target cells. In this work, we investigated the interaction of two pegylated gold nanoparticles, AuNP14a and AuNP14b, with human serum proteins albumin (HSA) and transferrin (Tf) as well as dimyristoyl-phosphatidylcholine (DMPC) liposomes, which can be a representative of biomembranes. We showed that AuNP14a/b interacted with HSA and Tf changing their electrical, thermodynamic, and structural properties as evidenced by dynamic light scattering, zeta potential, transmission electron microscopy, circular dichroism, fluorescence quenching, and isothermal titration calorimetry. These nanoparticles penetrated the DMPC membrane suggesting their ability to reach a target inside the cell. In most of the effects, AuNP14b was more effective than AuNP14a, which might result from its more positive charge. Further studies are needed to evaluate whether the interaction of AuNP14a/b with HSA and Tf is safe for the cell/organism and whether they may safely penetrate natural membranes. [ABSTRACT FROM AUTHOR]

The lipophilization of polyphenols (phenolipids) may increase their affinity for membranes, leading to better antioxidant protection. Cholesteryl esters of caffeic, dihydrocaffeic, homoprotocatechuic and protocatechuic acids were synthetized in a one-step procedure with good to excellent yields of ~50–95%. After evaluation of their radical scavenging capacity by the DPPH method and establishing the anodic peak potential by cyclic voltammetry, their antioxidant capacity against AAPH-induced oxidative stress in soybean PC liposomes was determined. Their interaction with the liposomal membrane was studied with the aid of three fluorescence probes located at different depths in the membrane. The cholesteryl esters showed a better or similar radical scavenging capacity to that of α-tocopherol and a lower anodic peak potential than the corresponding parental phenolic acids. Cholesteryl esters were able to protect liposomes to a similar or greater extent than α-tocopherol. However, despite their antiradical capacity and being able to penetrate and orientate in the membrane in a parallel position to phospholipids, the antioxidant efficiency of cholesteryl esters was deeply dependent on the phenolipid polyphenolic moiety structure. When incorporated during liposome preparation, cholesteryl protocatechuate and caffeate showed more than double the activity of α-tocopherol. Thus, cholesteryl phenolipids may protect biomembranes against oxidative stress to a greater extent than α-tocopherol. [ABSTRACT FROM AUTHOR]

Retinaldehyde (RAL), or retinal, is a vitamin A derivative that is widely used for several skin conditions. However, it is light sensitive and has low water solubility, limiting its efficiency in transdermal delivery. This study developed a novel delivery system for retinal (RAL) using flexible liposomes (FLPs) infused with α-tocopherol succinate (α-TS) to improve stability, and enhance skin permeability. The RAL-FLPs were embedded in pressure-sensitive adhesive (PSA) hydrogels, creating a delivery platform that supports prolonged skin residence and efficient permeation of RAL. The stability and skin permeation as well as human skin irritation and adhesion capabilities were assessed to determine the formulation's safety and efficacy. Our findings suggested that the addition of α-TS could improve liposomal stability and RAL chemical stability. Moreover, the skin permeation and fluorescence microscopic-based studies suggested that the addition of α-TS could enhance skin permeability of RAL through hair follicles. The RAL-FLP was embedded in PSA hydrogels fabricated from 25% GantrezTM S-97 (GT) and 1% hyaluronic acid (Hya) with aluminum as a crosslinker. The PSA hydrogel exhibited desirable peeling and tacking strengths. The developed hydrogels also demonstrated greater skin deposition of RAL compared with its aqueous formulation. Additionally, the RAL-FLP-embedded PSA hydrogels showed no skin irritation and maintained better adhesion for up to 24 h compared to commercial patches. Hence, the developed hydrogels could serve as a beneficial platform for delivering RAL in treating skin conditions. [ABSTRACT FROM AUTHOR]

Glioblastoma is the most aggressive and fatal brain cancer, characterized by a high growth rate, invasiveness, and treatment resistance. The presence of the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB) poses a challenging task for chemotherapeutics, resulting in low efficacy, bioavailability, and increased dose-associated side effects. Despite the rigorous treatment strategies, including surgical resection, radiotherapy, and adjuvant chemotherapy with temozolomide, overall survival remains poor. The failure of current chemotherapeutics and other treatment regimens in glioblastoma necessitates the development of new drug delivery methodologies to precisely and efficiently target glioblastoma. Nanoparticle-based drug delivery systems offer a better therapeutic option in glioblastoma, considering their small size, ease of diffusion, and ability to cross the BBB. Liposomes are a specific category of nanoparticles made up of fatty acids. Furthermore, liposomes can be surface-modified to target a particular receptor and are nontoxic. This review discusses various methods of liposome modification for active/directed targeting and various liposome-based therapeutic approaches in the delivery of current chemotherapeutic drugs and nucleic acids in targeting the glioblastoma and tumor microenvironment. [ABSTRACT FROM AUTHOR]

AbstractCarnosine is an endogenous dipeptide characterized by a multimodal mechanism of action. However, its clinical potential is limited by serum and cytosolic carnosinases, which significantly reduce its bioavailability. Based on that, different research groups have worked on the development of new strategies able not only to prevent its rapid metabolization but also to improve its distribution and specific targeting. In the present study, the development and in vitro characterization of new liposomal formulations loaded with carnosine are described. Nanoliposomes, produced through Thin-Layer Hydration followed by Extrusion method, were first investigated for their physicochemical stability. Photon correlation spectroscopy and electrophoretic light scattering, assessing the stability of the formulations, showed a strong homogeneity-oriented tendency for up to two months. Particle size, polydispersity index, and zeta potential were determined through dynamic light scattering and electrophoretic light scattering, demonstrating an almost neutral charge of the formulation and an effective encapsulation of carnosine. The morphology assessment performed via scanning electron microscopy showed good conformity and polydispersity. Differential scanning calorimetry measurements suggest the ability of carnosine to stabilize the large unilamellar vesicles. Lastly, the newly developed carnosine-loaded liposomal formulations also showed a good safety profile in human microglia. [ABSTRACT FROM AUTHOR]

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Aim: To evaluate the anti-pancreatic cancer effect of novel Tubeimoside I multifunctional liposomes combined with gemcitabine. Methods: Liposomes were prepared through the thin film hydration method, with evaluations conducted on parameters including encapsulation efficiency (EE%), particle size, polydispersity index (PDI), zeta potential (ZP), storage stability, and release over a 7-day period. The cellular uptake rate, therapeutic efficacy in vitro and in vivo and the role of immune microenvironment modulation were evaluated. Results: The novel Tubeimoside I multifunctional liposomal exhibited good stability, significant anti-cancer activity, and immune microenvironment remodeling effects. Furthermore, it showed a safety profile. Conclusion: This study underscores the potential of Novel Tubeimoside I multifunctional liposomal as a promising treatment option for pancreatic cancer. Article highlights Tubeimoside I was used instead of cholesterol as the membrane component of liposomes. Tubeimoside I can not only be used as a membrane stabilizer, but also as a chemotherapy adjuvant. Tubeimoside I and gemcitabine have synergistic anti-cancer effects. Tub I-GEM-LPs can reconstruct the immune microenvironment. Tub I-GEM-LPs can improve the hemolysis of Tub I. Tub I-GEM-LPs efficiently promoted tumor cell apoptosis. Tub I-GEM-LPs has better stability and significantly reduced drug leakage rate. These Tub I-GEM-LPs may aid in the treatment of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Ferroptosis is a cell death mechanism based on extensive cellular membrane peroxidation, implicated in neurodegenerative and other diseases. The essential oil component γ‐terpinene, a natural monoterpene with a unique highly oxidizable pro‐aromatic 1,4‐cyclohexadiene skeleton, inhibits peroxidation of polyunsaturated lipid in model heterogeneous systems (micelles and liposomes). Upon H‐atom abstraction, an unstable γ‐terpinene‐derived peroxyl radical is formed, that aromatizes to p‐cymene generating HOO⋅ radicals. As HOO⋅ are small and hydrophilic radicals, they quickly diffuse outside the lipid core, blocking the radical chain propagation of polyunsaturated lipids. This unprecedented antioxidant “slingshot” mechanism explains why γ‐terpinene shows a protective activity against ferroptosis, being effective at submicromolar concentrations in human neuroblastoma (SH‐SY5Y) cells. [ABSTRACT FROM AUTHOR]

Vitiligo is a common skin disorder where melanocytes, the cells that produce skin pigment, are destroyed by the immune system, leading to white patches on the skin and mucous membranes. This condition affects 0.4% to 2.0% of the global population, with a higher prevalence in females and often beginning in childhood. In India, about 1% of the population is affected, particularly in northern regions, with a higher incidence in females and links to other autoimmune diseases. This review examines recent progress in understanding vitiligo and its treatment. It focuses on the genetic, autoimmune, and environmental factors involved in the disease and highlights new therapies, such as targeted molecular treatments and advanced repigmentation methods. Current research shows that oxidative stress and genetic predispositions contribute to the autoimmune destruction of melanocytes. Novel drug delivery systems, including liposomes, nanoemulsions, and nanostructured lipid carriers, have improved treatment effectiveness. Clinical trials are exploring new treatments like Ruxolitinib cream and melanocyte transplantation, while teledermatology is becoming useful for managing patients. Vitiligo also poses a significant economic burden due to its impact on patients’ quality of life. Continued research is essential to develop better, more accessible treatments and reduce the economic impact of vitiligo. [ABSTRACT FROM AUTHOR]

Rose bengal (RB) is a widely used photosensitizer for determining quantum yields of singlet oxygen generation. While it is known to aggregate in polar environments at concentrations above 2 μM, the relationship between RB concentration and singlet oxygen photogeneration remains unclear. This study investigates the shift from monomeric to dimeric RB with increasing concentration and its impact on singlet oxygen generation in D2O‐based solutions and DMPC liposomes. Absorbance maxima for RB were observed at 514 nm (dimer) and 549 nm (monomer), with ionic environments influencing aggregation rates. Singlet oxygen phosphorescence showed non‐linear dependency above 2 μM, indicating the effects of aggregation. Results suggest that RB concentrations should be kept at 1 μM or lower in photochemical studies to avoid aggregation‐related discrepancies in singlet oxygen yield determination. These findings highlight the importance of considering RB aggregation in photochemical research and medical applications. [ABSTRACT FROM AUTHOR]

The efficacy of anthracycline, such as doxorubicin (DOX), is facilitated by cancer cell‐intrinsic type I interferon (IFN‐I) signaling through the induction of immune responses. However, weak and chronic IFN‐I responses from rounds of chemotherapy lead to resistance against DNA damage and acquired resistance to the therapy. An exogenous supply of IFN‐I can improve the chemotherapeutic responses. Herein, a library of cationic liposomes is developed for the optimization of 1, 2‐dioleoyl‐3‐trimethylammonium‐propane (DOTAP) proportions to enhance the lysosome escape and tumor distribution of the stimulator of interferon genes (STING) agonist 2′,3′‐cyclic guanosine monophosphate‐adenosine monophosphate (cGAMP) and DOX. The cationic liposomes with 8% DOTAP release cGAMP into the cytoplasm and increase the concentration of DOX in the tumor by 1.5 times compared with the free drug. Upon accumulation at the tumor site, the optimized liposomes induce immunogenic cell death (ICD) and stimulate the STING signaling, thereby improving the production of endogenous IFN‐I and promoting dendritic cell maturation to mobilize T cell immunity. The tumor growth inhibition rate is 86%, and the median survival time is 1.6‐fold prolonged. This study offers a strategy to enhance the DOX‐induced immune response by activating the STING pathway to supply IFN‐I. [ABSTRACT FROM AUTHOR]