Lipid Nanocarriers Research Articles

Phytomedicinal flavonoid loaded phospholipid sheathed lipidic nano-carriers as a platform with boosted oral anti-mycobacterium activity

Phytomedicinal flavonoid loaded phospholipid sheathed lipidic nano-carriers as a platform with boosted oral anti-mycobacterium activity

Nose-to-Brain delivery of antiretroviral drug loaded lipidic nanocarriers to purge HIV reservoirs in CNS: A safer approach

Nose-to-Brain delivery of antiretroviral drug loaded lipidic nanocarriers to purge HIV reservoirs in CNS: A safer approach

A Review on Solid-lipid Nanoparticle

Abstract: Hydrophilic and hydrophobic medicines can both be carried by solid lipid nanoparticles (SLNs), which are solid core lipid nanocarriers. They are one of the favoured options for medication delivery since they may be constructed of components that are biocompatible. Surface alterations of SLNs may also provide them distinctive qualities like mucoadhesiveness or targeting capacity. A wide range of drug delivery technologies are being developed at an astounding rate. The two main compounds that are widely delivered to target areas are various manufactured nanoparticles and medications with poor pharmacokinetic and solubility characteristics. The features of biodegradability and nontoxicity make nanolipid dispersions (liposomes, deformable liposomes, virosomes, ethosomes, and solid lipid nanoparticles) the best colloidal carriers for administration. Solid lipid nanoparticles (SLNs), which may be manipulated to demonstrate a variety of benefits over liposomes and polymeric nanoparticles, are the most prevalent among them.

Gatifloxacin Loaded Nano Lipid Carriers for the Management of Bacterial Conjunctivitis.

Bacterial conjunctivitis (BC) entails inflammation of the ocular mucous membrane. Early effective treatment of BC can prevent the spread of the infection to the intraocular tissues, which could lead to bacterial endophthalmitis or serious visual disability. In 2003, gatifloxacin (GTX) eyedrops were introduced as a new broad-spectrum fluoroquinolone to treat BC. Subsequently, GTX use was extended to other ocular bacterial infections. However, due to precorneal loss and poor ocular bioavailability, frequent administration of the commercial eyedrops is necessary, leading to poor patient compliance. Thus, the goal of the current investigation was to formulate GTX in a lipid-based drug delivery system to overcome the challenges with the existing marketed eyedrops and, thus, improve the management of bacterial conjunctivitis. GTX-NLCs and SLNs were formulated with a hot homogenization-probe sonication method. The lead GTX-NLC formulation was characterized and assessed for in vitro drug release, antimicrobial efficacy (against methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa), and ex vivo permeation. The lead formulation exhibited desired physicochemical characteristics, an extended release of GTX over a 12 h period, and was stable over three months at the three storage conditions (refrigerated, room temperature, and accelerated). The transcorneal flux and permeability of GTX from the GTX-NLC formulation were 5.5- and 6.0-fold higher in comparison to the commercial eyedrops and exhibited a similar in vitro antibacterial activity. Therefore, GTX-NLCs could serve as an alternative drug delivery platform to improve treatment outcomes in BC.

Vascular Risks, Aging, and Late-Onset Dementia: Overlapping Etiologies Point to 'Scavenger Receptor'-Mediated Therapeutics

Early changes in systemic vascular stiffness and endothelial function can contribute to altered cerebrovascular hemodynamics and impaired cognitive function; additionally, these vascular changes point to potential targets for prevention and treatment strategies in people with mild cognitive impairment. Although the pathogenic mechanisms underlying these vascular changes are heterogeneous and complex, one common feature is the development of cerebral blood flow (CBF) dysregulation, resulting in chronic cerebral hypoperfusion (CCH) and subsequently an insufficient blood supply to the brain. However, the incorporation of drugs, or other bioactive molecules, into specifically a "high density lipoprotein-like" ("HDL-like") lipid nanocarrier can result in the production of a multitasking "combination therapeutic" – capable of targeting cell-surface scavenger receptors (mainly SR-BI). Such targeting behavior of this proposed (biomimetic-nanocarrier) therapeutic vehicle can facilitate the nanocarrier's enhanced endocytosis into various target cells which, in turn, increases the likelihood that this multitasking "combination therapeutic" provides some enhanced efficacy at different stages of dementia.

Riluzole-loaded lipid nanoparticles for brain delivery: Preparation, optimization and characterization

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, with a median survival of only 2 to 4 years. Riluzole, a drug commonly used in the management of ALS, has a low aqueous solubility and limited bioavailability. ALS treatment is also hindered by the presence of the blood–brain barrier (BBB) that preserves the delicate homeostasis of the cerebral milieu, isolating it and making brain drug delivery exceptionally hard. To overcome these issues, the use of lipid nanocarriers, such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), is a promising strategy. In this study, SLN and NLC were prepared and optimized to facilitate riluzole uptake into the brain for ALS therapy. The lipid nanoparticles were characterized through different techniques, with respect to their physicochemical properties (size, zeta potential (ZP), polydispersity index (PDI)), as well as encapsulation efficiency, morphology, stability, in vitro release, crystallinity, and biocompatibility. Riluzole-loaded nanocarriers exhibited characteristics suitable for brain delivery, including mean diameters between 147.2 and 203.1 nm, low PDI (<0.3), and negative ZP between −22.5 and −27.5 mV. Additionally, they were physically stable over 3 months under storage conditions (5 ℃ and 25 ℃), promoting a slow and sustained release of the drug, which was shown to be inside the core of the lipid matrix. Cytotoxicity assays demonstrated that both SLN and NLC did not significantly affect the viability of an hCMEC/D3 cell monolayer at a riluzole concentration up to 10 μM. The results suggest that the developed nanocarriers could be a viable platform to target riluzole to the central nervous system (CNS). Nevertheless, further in vitro and in vivo studies are needed to validate their therapeutic efficacy and safety.

A Comprehensive Literature Review of Lipids Used in the Formulation of Lipid Nanoparticles

Abstract: Lipid nanocarriers are reaching new heights in the field of drug delivery. The core of this technology resides in simple molecules, i.e., lipids. Solid and liquid lipids of biocompatible and generally recognized as safe (GRAS) status are employed for the development of lipid nanoparticles along with surfactant(s), solvents, and drug molecules. Researchers have practiced a variety of solid and liquid lipids with acceptable profiles in the formulation of lipid nanoparticles. Solid lipids like triglycerides, fatty acids, fatty alcohols, waxes, and butter have been used in designing lipid nanocarriers. The potential of various plant-based oils has also been tested in designing nanostructured lipid carriers (NLC). With the exponential advancement in lipid-based delivery systems, there exists a need for an appropriate lipid system to obtain an effective product. This review gives a brief insight into lipids, which have been exploited by researchers for designing solid lipid nanoparticles (SLN) and nanostructured lipid carriers. A tabular presentation of important key points of past studies exploiting these lipids for preparing SLN/NLC is the highlight of the article.

Effective Attenuation of Arteriosclerosis Following Lymphatic-Targeted Delivery of Hyaluronic Acid-Decorated Rapamycin Liposomes.

The activation of lymphatic vessel function is the crux to resolving atherosclerosis (AS), a chronic inflammatory disease. Rapamycin (RAPA) recently has attracted considerable attention as a potent drug to induce atherosclerotic plaque attenuation. The objective of this work was to develop a ligand-decorated, RAPA-loaded liposome for lymphatic-targeted delivery of drugs to improve abnormal lymphatic structure and function, resulting in highly effective regression of atherosclerotic plaques. Hyaluronic acid-decorated, RAPA-loaded liposomes (HA-RL) were fabricated by emulsion-solvent evaporation. The average size, zeta potential, entrapment efficiency were characterized, and the stability and drug release in vitro were investigated. Furthermore, the in vitro and in vivo lymphatic targeting ability were evaluated on lymphatic endothelial cells and LDLR-/- mice, and the efficiency of this nano-system in inducing the attenuation of atherosclerotic plaques was confirmed. HA-RL had a size of 100 nm, over 90% drug encapsulation efficiency, the storage stability was distinguished, demonstrating a slow release from the lipid nano-carriers. The mean retention time (MRT) and elimination half-life (t1/2β) achieved from HA-RL were 100.27±73.08 h and 70.74±50.80 h, respectively. HA-RL acquired the most prominent efficacy of lymphatic-targeted delivery and atherosclerotic plaques attenuation, implying the successful implementation of this novel drug delivery system in vivo. HA-RL exhibited the most appreciable lymphatic targeting ability and best atherosclerotic plaques attenuation efficiency, opening a new paradigm and promising perspective for the treatment of arteriosclerosis.

Ionizable polymeric nanocarriers for the codelivery of bi-adjuvant and neoantigens in combination tumor immunotherapy.

Ionizable lipid nanocarriers have made historical contribution to COVID-19 mRNA vaccines. Here, we report ionizable polymeric nanoparticles that co-deliver bi-adjuvant and neoantigen peptides for cancer immunotherapy in combination with immune checkpoint blockade (ICB). Current cancer ICB benefits only a small subset of patients, largely due to a lack of pre-existing target cells and checkpoint targets for ICB, tumor antigenic heterogeneity, and tumor immunosuppression. Therapeutic vaccines hold the potential to enhance ICB therapeutic efficacy by expanding antitumor cell repertoires, upregulating immune checkpoint levels and hence sensitizing ICB, and reducing tumor immunosuppression. Chemically defined peptide vaccines are attractive, but their current therapeutic efficacy has been limited due to 1) poor vaccine delivery to immunomodulatory lymph nodes (LNs) and antigen (Ag)-presenting cells (APCs), 2) poor immunostimulant adjuvant efficacy with restricted target cell subsets in humans, 3) limited adjuvant/Ag codelivery to enhance Ag immunogenicity, and 4) limited ability to overcome tumor antigenic heterogeneity. Here, we developed nanovaccines (NVs) using pH-responsive polymeric micellular nanoparticles (NPs) for the codelivery of bi-adjuvant [Toll-like receptor (TLR) 7/8 agonist R848 and TLR9 agonist CpG] and peptide neoantigens (neoAgs) to draining LNs for efficient Ag presentation in a broad range of APC subsets. These NVs potentiated the immunogenicity of peptide Ags and elicits robust antitumor T cell responses with memory, and remodeled the tumor immune milium with reduced tumor immunosuppression. As a result, NVs significantly enhanced ICB therapeutic efficacy for murine colorectal tumors and orthotopic glioblastoma multiforme (GBM). These results suggest marked potential of bi-adjuvant/neoAg-codelivering NVs for combination cancer immunotherapy.

Lipid nanocarrier targeting activated macrophages for antiretroviral therapy of HIV reservoir.

Aim: To develop lipid nano-antiretrovirals (LNAs) for the treatment of HIV-infected macrophages. Materials & methods: LNAswere prepared with docosahexaenoic acid to facilitate brain penetration and surface-decorated with folate considering that infected macrophages often overexpress folate receptors. Results: Folate-decorated LNAs loading rilpivirine (RPV) wereefficiently taken up byfolate receptor-expressing cell types including activated macrophages. The intracellular Cmax of theRPV-LNAs in activated macrophages was 2.54-fold and the area under thecurve was3.4-fold versus free RPV, translating to comparable or higher (p<0.01; RPV ≤6.5ng/ml) activities against HIV infectivity and superior protection (p<0.05) against HIV cytotoxicity. LNAs were also effective in monocyte-derived macrophages. Conclusion: These findings demonstratethe potential of LNAs for the treatment of infected macrophages, which are key players in HIV reservoirs.

Enhancing Apoptosome Assembly via Mito‐Biomimetic Lipid Nanocarrier for Cancer Therapy

AbstractApoptosis is the natural programmed cell death process, which is responsible for abnormal cell clearance. However, many cancer cells develop various mechanisms to escape apoptosis through interrupting apoptosome assembly, which is a key step to initiate apoptosis. This promotes tumorigenesis and drug resistance, and thus, poses a great challenge in cancer treatment. Herein, a biomimetic lipid nanocarrier mimicking mitochondrial Cytochrome C (Cyt C) binding is developed. Cardiolipin, the major phospholipid of mitochondrial inner membrane, is introduced as the main component in biomimetic liposomal formulation. With the help of cardiolipin, Cyt C is sufficiently loaded in liposome based on electrostatic and hydrophobic interaction with cardiolipin. Lonidamine (LND) is added in hydrophobic phase of liposome to modulate the metabolic activity within cancer cells and sensitize the cells to Cyt C‐induced apoptosis. The results suggest that LND reduces ATP level and creates favorable environment for Cyt C induced apoptosome assembly, exhibiting higher apoptosis level and anti‐tumor efficacy in vitro and in vivo. The conjugation of a tumor‐homing peptide, LinTT1, on the nanovesicle, increases the efficacy due to enhanced tumor accumulation. Overall, this biomimetic lipid nanocarrier proves to be an efficient delivery system with great potential of pro‐apoptosis cancer therapy.

Theoretical design for covering Engeletin with functionalized nanostructure-lipid carriers as neuroprotective agents against Huntington's disease via the nasal-brain route.

Objective: To propose a theoretical formulation of engeletin-nanostructured lipid nanocarriers for improved delivery and increased bioavailability in treating Huntington's disease (HD). Methods: We conducted a literature review of the pathophysiology of HD and the limitations of currently available medications. We also reviewed the potential therapeutic benefits of engeletin, a flavanol glycoside, in treating HD through the Keap1/nrf2 pathway. We then proposed a theoretical formulation of engeletin-nanostructured lipid nanocarriers for improved delivery across the blood-brain barrier (BBB) and increased bioavailability. Results: HD is an autosomal dominant neurological illness caused by a repetition of the cytosine-adenine-guanine trinucleotide, producing a mutant protein called Huntingtin, which degenerates the brain's motor and cognitive functions. Excitotoxicity, mitochondrial dysfunction, oxidative stress, elevated concentration of ROS and RNS, neuroinflammation, and protein aggregation significantly impact HD development. Current therapeutic medications can postpone HD symptoms but have long-term adverse effects when used regularly. Herbal medications such as engeletin have drawn attention due to their minimal side effects. Engeletin has been shown to reduce mitochondrial dysfunction and suppress inflammation through the Keap1/NRF2 pathway. However, its limited solubility and permeability hinder it from reaching the target site. A theoretical formulation of engeletin-nanostructured lipid nanocarriers may allow for free transit over the BBB due to offering a similar composition to the natural lipids present in the body a lipid solubility and increase bioavailability, potentially leading to a cure or prevention of HD. Conclusion: The theoretical formulation of engeletin-nanostructured lipid nanocarriers has the potential to improve delivery and increase the bioavailability of engeletin in the treatment of HD, which may lead to a cure or prevention of this fatal illness.

Eco-Friendly Sustainable Nanocarriers to Treat Oxidative Stresses and Skin Aging-Related Ailments, Valorization of a By-Product.

The peel from Citrus-sinensis L. is a medicinally significant food waste, and its extract (O-Ext) could be significant against oxidative stresses and skin aging, However, the penetration barriers, instability in formulation, undefined toxicities, and enzymatic activities make the O-Ext difficult to formulate and commercialize. The goal of this study was to evaluate O-Ext against oxidative stress, prepare O-Ext-loaded nano-lipid carriers (O-NLCs), and load them into topical O/W-emulsion (O-NLC-E) to improve O-Ext permeation and its in vivo antiaging effects. TPC, TFC, DPPH activity, and mineral/metal contents of O-Ext were determined via atomic-absorption spectroscopy. For bioactive compounds profiling, GC-MS analysis was carried out. O-NLCs were prepared and tested for physicochemical attributes, while HaCaT and fibroblast cells were used to study permeation and cytotoxicity. The kinetic characteristics of ex vivo permeation through rat skin were established, following the Higuchi model. Following written consent, safety investigations were conducted on human volunteers for three months, where optimized O-NLC-E and B-NLC-E were regularly applied on cheeks. Non-invasive procedures were used to assess the volunteer's skin erythema, TEWL, sebum level, melanin, hydration, pH, elasticity, and pore sizes after specified intervals. The results demonstrated that applying O-NLC-E formulation to the skin of volunteers directed significant antiaging benefits. The study offers nanotechnology-based sustainability approach against skin ageing.

Multifaceted nanolipidic carriers: a modish stratagem accentuating nose-to-brain drug delivery

Multifaceted nanolipidic carriers: a modish stratagem accentuating nose-to-brain drug delivery

Nanocarriers significantly augment the absorption of ocular-delivered drugs: A comparative meta-analysis study

This study presents a meta-analysis that compiles information collected from several studies aiming to prove, by evidence, that nanocarriers out-perform conventional formulations in augmenting the bioavailability of ocular topically administered drugs. Data was further categorized into two subgroups; polymeric-based nanocarriers versus their lipid-based counterparts, as well as, naturally-driven carriers versus synthetically-fabricated ones. After normalization, the pharmacokinetic factor, area under the curve (AUC), was denoted as the “effect” in the conducted study, and the corresponding Forest plots were obtained. Our meta-analysis study confirmed the absorption enhancement effect of loading drugs into nanocarriers as compared to conventional topical ocular dosage forms. Interestingly, no significant differences were recorded between the polymeric and lipidic nanocarriers included in the study, while naturally-driven nanoplatforms were proven superior to the synthetic alternatives.

Metered Dose Inhalers (MDI’S) for High-Performance Pulmonary Drug Delivery in Assistance to Nanotechnology

Respiratory infections pose a severe danger to public health's morbidity and death on a global scale. Delivery via the lungs can be accomplished using several drug delivery tools, including nebulizers, MDI’s and dry powder inhalers. Metered dosage inhalers are the most intriguing and the clinician's first preference out of all of them. This review emphasized based on metered dose inhalers for the delivery of pulmonary drugs. This study focuses on the provision of various therapies employing lipid nanocarriers, polymeric nanoparticles dendrimers &amp; micelles, among others, using metered dose inhalers, liposomes, solid lipid nanostructures, nanostructured lipid carriers, and other topics were thoroughly explored. The market scenario for different MDI’s as well as information on digital metered dose inhalers is also covered in this review.

Interference with Bacterial Conjugation and Natural Alternatives to Antibiotics: Bridging a Gap.

Horizontal gene transfer (HGT) in food matrices has been investigated under conditions that favor gene exchange. However, the major challenge lies in determining the specific conditions pertaining to the adapted microbial pairs associated with the food matrix. HGT is primarily responsible for enhancing the microbial repertoire for the evolution and spread of antimicrobial resistance and is a major target for controlling pathogens of public health concern in food ecosystems. In this study, we investigated Salmonella Heidelberg (SH) and Escherichia coli (EC) regarding gene exchange under conditions mimicking the industrial environment, with the coproducts whey (SL) and chicken juice (CJ). The S. Heidelberg strain was characterized by antibiotic susceptibility standards and PCR to detect the blaTEM gene. A concentration of 0.39 mg/mL was determined to evaluate the anti-conjugation activity of nanostructured lipid nanocarriers (NLCs) of essential oils to mitigate β-lactam resistance gene transfer. The results showed that the addition of these coproducts promoted an increase of more than 3.5 (whey) and 2.5 (chicken juice) orders of magnitude in the conjugation process (p < 0.01), and NLCs of sage essential oil significantly reduced the conjugation frequency (CF) by 74.90, 90.6, and 124.4 times when compared to the transfers in the absence of coproducts and the presence of SL and CJ, respectively. For NLCs from olibanum essential oil, the decrease was 4.46-fold for conjugations without inhibitors and 3.12- and 11.3-fold in the presence of SL and CJ. NLCs associated with sage and olibanum essential oils effectively control the transfer of antibiotic resistance genes and are a promising alternative for use at industrial levels.

Chicken embryo model for in vivo acute toxicological and antitumor efficacy evaluation of lipid nanocarrier containing doxorubicin

Nanoencapsulation of chemotherapeutics, including doxorubicin, can endow the formulations with unique properties, such as a decrease in adverse effects and toxicity. The chicken embryo model is an alternative and well-accepted strategy for evaluating the toxicity and efficacy of drugs and nanoformulations. Therefore, this study proposes the development of a new lipid nanocarrier for doxorubicin delivery (NanoLip-Dox) and posterior evaluation of toxicological profile and antitumoral efficacy against a breast tumor in chicken embryos. NanoLip-Dox showed a unimodal particle size (< 150 nm), negative zeta potential (−19.5 mV), absence of drug crystals, drug content of 0.099 mg·mL−1, and high entrapment efficiency (95%). NanoLip-Dox did not cause toxicity in the chicken embryos; in contrast, doxorubicin hydrochloride induced moderate irritation in the chorioallantoic membrane (at 862.1 μmol·L−1), a survival rate of 50% (at 1.7 μmol·L−1), and an increase in aspartate aminotransferase (at 862.1, 344.8, and 172.4 μmol·L−1). In addition, NanoLip-Dox (at 1.7 μmol·L−1) showed potent antitumor efficacy with a high tumor remission percentage (40.9 ± 9.7%) compared to the control group (8.6 ± 14.8%). These findings together with the absence of toxicity concerning morphological characteristics, weights of embryos and organs, hematologic parameters, and enzymatic activity (alanine aminotransferase, aspartate aminotransferase, and creatinine) suggest the safety and efficacy of NanoLip-Dox.

Homogalacturonan enriched pectin based hydrogel enhances 6-gingerol's colitis alleviation effect via NF-κB/NLRP3 axis

A nanolipidcarrier (NLC) loaded homogalacturonan enriched pectin (citrus modified pectin, MCP4) hydrogel was designed as a novel colon inflammation site-specific oral delivery system for 6-gingerol (6G) (6G-NLC/MCP4 hydrogel) administration, and its colitis alleviation effect were investigated. 6G-NLC/MCP4 exhibited typical “cage-like” ultrastructure with 6G-NLC embedded in the hydrogel matrix as observed by cryoscanning electron microscope. And due to the homogalacturonan (HG) domain in MCP4 specifically combined with Galectin-3, which is overexpressed in the inflammatory region, the 6G-NLC/MCP4 hydrogel targeted to severe inflammatory region. Meanwhile, the prolonged-release characteristics of 6G-NLC provided sustained release of 6G in severe inflammatory regions. The matrix of hydrogel MCP4 and 6G achieved synergistic alleviation effects for colitis through NF-κB/NLRP3 axis. Specifically, 6G mainly regulated the NF-κB inflammatory pathway and inhibited the activity of NLRP3 protein, while MCP4 regulated the expression of Galectin-3 and peripheral clock gene Rev-Erbα/β to prevent the activation of inflammasome NLRP3.

Quality-by-design driven analytical method (AQbD) development and validation of HPLC–UV technique to quantify rivastigmine hydrogen tartrate in lipidic nanocarriers: Forced degradation, and assessment of drug content and in vitro release studies

The main purpose of current investigation was to design and further validate a technique for the quantitative determination of rivastigmine hydrogen tartrate (RHT), a cholinesterase inhibitor in the nano formulations. With the employment of a reverse phase C18 column and a very simple mobile phase, an isocratic HPLC–UV analysis technique was developed, optimized, and validated following ICH Q2 (R1) requirements along with the inculcation ofAnalytical Quality-by-Design (AQbD) methodology. A two-level full factorial screening design was applied to filter out the variables influencing responses, followed by the application of central composite design (CCD) to further optimize the method using Design-Expert® software. Analyses were performed at room temperature with 0.9 mL. min−1 flow rate and detection wavelength of 215 nm. The optimized HPLC technique exhibited superior linearity, selectivity, and precision. The inherent stability of RHT was evaluated using the optimized method byconductingforced degradation studies. The RHT peak was clear and unaffected by matrix interference in the specimens from the forced degradation studies, drug content analysis, and in vitro release study. The assay had a limit of detection (LOD) of 14.32 ng. mL−1 and a limit of quantitation (LOQ) of 43.40 ng. mL−1. With acceptable intra- and interday precision, the methodologywas confirmedto berobust. The devised stability-indicating HPLC technique for analyzing RHT content, its stability in the nano formulations, and drug release in vitro proved to be selective, accurate, sensitive, and consistent.