Nanostructured Lipid Carriers Research Articles

Appraisal of Chitosan-Coated Lipid Nano-Combination with Miltefosine and Albendazole in the Treatment of Murine Trichinellosis: Experimental Study with Evaluation of Immunological and Immunohistochemical Parameters

PurposeResistance and adverse consequences of albendazole (ABZ) in treating trichinellosis urged demand for secure and effective new drugs. The current study aimed to assess the effect of chitosan-coated lipid nano-combination with albendazole and miltefosine (MFS) in treating experimental murine trichinellosis and evaluating pathological and immunological changes of trichinellosis.Materials and MethodsOne hundred twenty Swiss albino mice were divided into six groups. Each group was subdivided into a and b subgroups based on the scarification time, which was 7- and 40-days post-infection (PI), respectively. The treatment efficacy was evaluated using parasitological, histopathological, serological (interleukin (IL)-12 and IL-4 serum levels), immunohistochemical (GATA3, glutathione peroxidase1 (GPX1) and caspase-3), and scanning electron microscopy (SEM) methods.ResultsThe most effective drug was nanostructured lipid carriers (NLCs) loaded with ABZ (G5), which showed the most significant reduction in adults and larval count (100% and 92.39%, respectively). The greatest amelioration in histopathological changes was reported in G4 treated with MFS. GATA3 and caspase-3 were significantly reduced in all treated groups. GPX1 was significantly increased in G6 treated with MFS + NLCs. The highest degenerative effects on adults and larvae by SEM were documented in G6.ConclusionLoading ABZ or MFS on chitosan-coated NLCs enhanced their efficacy against trichinellosis. Although ABZ was better than MFS, their combination should be considered as MFS caused a significant reduction in the intensity of infection. Furthermore, MFS showed anti-inflammatory (↓GATA3) and antiapoptotic effects (↓caspase-3), especially in the muscular phase. Also, when loaded with NLCS, it showed an antioxidant effect (↑GPX1).Graphical abstract

Preparation of Dexamethasone-Loaded Nanoparticles and Therapeutic Adoption for Acute Lung Injury in Septic Mice Through the TLR9 Pathway

This research aimed to better exert the efficacy of dexamethasone (DEX) and fabricate an intercellular adhesion molecule A (ILDMA) monoclonal antibody (mAb)-modified nanostructured lipid carrier (NSLC). The anionic DEX NSLC was fabricated by the aqueous solvent diffusion methodology using DEX as the model drug and in combination with various types of lipids. Using N,N’-succinimidyl carbonate as the link, anti-ILDMA mAb-modified anion DEX NSLC (ILDM/DEX/NSLC) and anti-IgG mAb-modified cation DEX NSLC (IgG/DEX/NSLC) were prepared. The total lipid content was controlled unchanged, 3% mass ratio of glyceryl monostearate (MS) in the original prescription was replaced with 3% mass ratio of octadecylamine (ODA), and ILDM/DEX/ODA-NSLC and IgG/DEX/ODA-NSLC were fabricated in the same way. The four NSLCs prepared in the experiment were round in shape and uniform in size. The nanoparticles with a size of approximately 230 nm were similar, and the zeta potentials were (−29.8±21.5) mV, (−27.9±1.6) mV, (36.8±0.8) mV, and (33.7±2.9) mV, respectively. In vitro drug release demonstrated a cumulative release rate of more than 55% of DEX NSLC. The inhibitory rate of DEX NSLC on the activated human vascular endothelial cell line (EAhy926 cell) was dose dependent, and ILDM/DEX/NSLC could transport DEX to activated endothelial cells more efficiently, thus enhancing the intervention ability on diseased endothelium. For the establishment of a sepsis-induced acute lung injury (ALI) mouse model, ILDM/DEX/NSLC was highly distributed in the lung of the model, and its infiltration effect on inflammatory cells was superior to that of other drugs (P < 0.05). Meanwhile, ILDM/DEX/NSLC could more markedly repair the pathological features in the mouse model than other drugs did (P < 0.05). The nanodrug inhibited the protein level of TLR9 in mouse lung tissue to the maximum extent (P < 0.05), thereby enhancing the survival rate of the mice.

Enhancing acid stability of citral through internal structure modulation in nanostructured lipid carriers with solid lipids and phospholipids

In this current study, the internal structure of nanostructured lipid carriers was modulated by phospholipids (lecithin PC, hydrogenated soybean phospholipid HPC) and solid lipids to achieve stable encapsulation of citral. The presence of high melting point HPC could construct α-crystalline type with more lattice defects and effectively inhibit β-ization. The HPC group could maintain the particle size at 155.9–186.9 nm, the polydispersity index (PDI) at 0.182–0.321, the Zeta potential at −57.58 mV to −49.35 mV and the retention rate of citral at 91.33–98.49 % in the acidic environments of 2 mM and 20 mM hydrochloric acid solutions. The recrystallization index (RI) of NLC increased with the number of solid lipid ester bonds (from 3.57 % to 16.58 % in the PC group and from 0.82 % to 12.47 % in the HPC group). The results illustrated that the number of solid lipid ester bonds and the melting point of phospholipids affected crystallinity of the lipid matrix and thus the stability of encapsulated citral. Hydrogenated phospholipid with high melting points was more beneficial in stabilizing citral. The present study improved the acidic stability of citral and provided a new thought for the application of citral in acidic beverages.

Topical co-delivery of tacrolimus and calcipotriol loaded nanostructured lipid carrier: a potential and synergistic approach in the management of psoriasis

The focus of this study was to develop a Vitamin-D3 (Calcipotriol)-based Tacrolimus (TAC)-loaded nanostructured lipid carrier (NLC) for topical application to treat psoriasis. The sonication technique followed by melt emulsification was used to formulate TAC-NLC, in which Precirol ATO-5, Calcipotriol, and Solutol HS-15 were used as excipients. Based on the analysis of particle size, PDI, and entrapment efficiency of various TAC-NLCs using Box-Behnken Design, an optimized NLC was selected. The selected nanocarrier was further transformed into the gel and then characterized for in vitro release, in vitro and ex vivo permeation, and dermatokinetic, including in vitro characterization studies. The optimized TAC-NLC had a particle size of 231 ± 1.52 nm with a narrow PDI of 0.40 ± 0.001 along with high entrapment efficiency (84.04 ± 1.36%) and drug loading (12.61 ± 0.20%)”. The in vitro release showed sustained release throughout 12 h. Moreover, dissimilarity (f1:52) and the similarity factor (f2:37) showed a lack of any similarity in the evaluation of drug release from TAC-NLC formulation and Conventional formulation. The time requisite to release 50% (T50), 30% (T30), and 20% (T20) of the drug is also calculated. The flux and permeability coefficients were found to be 11.59 µg/cm2/h and 0.0386 cm/h. A dermatokinetic study of TAC-NLC indicated a remarkable rise in AUC0-12h and CSkin max compared to conventional formulation (p < 0.005). Further, the vitro studies indicated higher cell viability (85%-80%) on melanoma cells than aqueous suspension of the drug (60–70%). The study indicated that the topical application of TAC-NLC nanogel was found potentially useful for the management of psoriasis.

Co-Delivery of Aceclofenac and Methotrexate Nanoparticles Presents an Effective Treatment for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a common acute inflammatory autoimmune connective tissue arthropathy. The genetic studies, tissue analyses, experimental animal models, and clinical investigations have confirmed that stromal tissue damage and pathology driven by RA mounts the chronic inflammation and dysregulated immune events. We developed methotrexate (MTX)-loaded lipid-polymer hybrid nanoparticles (MTX-LPHNPs) and aceclofenac (ACE)-loaded nanostructured lipid carriers (ACE-NLCs) for the efficient co-delivery of MTX and ACE via intravenous and transdermal routes, respectively. Bio-assays were performed using ex-vivo skin permeation and transport, macrophage model of inflammation (MMI) (LPS-stimulated THP-1 macrophages), Wistar rats with experimental RA (induction of arthritis with Complete Freund's adjuvant; CFA and BCG), and programmed death of RA affected cells. In addition, gene transcription profiling and serum estimation of inflammatory, signaling, and cell death markers were performed on the blood samples collected from patients with RA. Higher permeation of ACE-NLCs/CE across skin layers confirming the greater "therapeutic index" of ACE. The systemic delivery of MTX-loaded LPHNPs via the parenteral (intravenous) route is shown to modulate the RA-induced inflammation and other immune events. The regulated immunological and signaling pathway(s) influence the immunological axis to program the death of inflamed cells in the MMI and the animals with the experimental RA. Our data suggested the CD40-mediated and Akt1 controlled cell death along with the inhibited autophagy in vitro. Moreover, the ex vivo gene transcription profiling in drug-treated PBMCs and serum analysis of immune/signalling markers confirmed the therapeutic role co-delivery of drug nanoparticles to treat RA. The animals with experimental RA receiving drug treatment were shown to regain the structure of paw bones and joints similar to the control and were comparable with the market formulations. Our findings confirmed the use of co-delivery of drug nanoformulations as the "combination drug regimen" to treat RA.

Nanostructured Lipid Carrier for Hyperpigmentation Treatment - a Dermal Prospective

The normal human skin is exposed to different types of infection like wrinkles, pigmentation, acne, pimples in which pigmentation is most common in women over 30-40 years. The field of nanotechnology is currently intensely exploited for drug delivery technology for passive and active targeting via various routes of administration, such things can be effectively treated by incorporating the drug, loaded in a Nanostructured lipid carrier (NLC). NLCs have shown potential in delivering poorly soluble active components and in depigmenting. NLC springs up as the second generation of lipid nanoparticles to overcome the shortcomings of first generation through the topical route. NLC in topical administration provides some added advantages like increasing skin hydration and modified release profile and increase in skin penetration leading to avoidance of systemic absorption. NLCs are composed of biocompatible lipids, surfactants, and cosurfactants which help enhance drug loading capacity and stabilize the formulation. NLC's remarkable physicochemical and subsequently biocompatible qualities have created an ongoing need for the development of beneficial and safe drug delivery methods. The key attributes of NLC that make them a promising drug delivery system are ease of preparation, biocompatibility, the feasibility of scale-up, non-toxicity, improved drug loading, and stability Their ingredients have a special impact on the end product's physicochemical characteristics and efficacy. The present review aims to focus on the recent advancement in the preparation, characterization, and applications of NLC in treating hyperpigmentation.

Reshaping antibiotic delivery: Chitosan‐based polymeric hydrogel for transdermal treatment of drug resistant bacteria

AbstractThe aim of the present study was to formulate and assess the antibacterial efficacy of a transdermal chitosan based polymeric hydrogel for transdermal treatment of bacterial resistance strains. Utilizing the micro‐emulsion method and the Box–Behnken design model, imipenem‐cilastatin (IMI‐CIL) loaded nanostructured lipid carriers (NLCs) were fabricated and optimized, employing Compritol 888 ATO as the lipid core and Tween 80 as the stabilizer. The optimized nanoformulation underwent a comprehensive evaluation encompassing parameters such as particle diameter, zeta potential, surface morphology, entrapment efficiency, crystallinity, and molecular interaction. The optimized nanoparticles displayed a mean particle size of 129 nm, a zeta potential of −19.8 mV, and a polydispersity index (PDI) of 0.286. Detailed investigations into crystallinity and Fourier transform infrared (FTIR) analysis did not reveal any indications of molecular interaction. Both the IMI‐CIL loaded NLCs and the hydrogel exhibited sustained in‐vitro drug release. Moreover, the hydrogel, enriched with permeation enhancers, demonstrated a remarkable 15.77‐fold increase in drug permeation. Furthermore, the IMI‐CIL loaded NLCs exhibited significantly elevated antibacterial activity when juxtaposed with IMI‐CIL solution, which demonstrated minimal activity against non‐resistant bacterial species and lacked activity against resistant isolates. In summary, the IMI‐CIL loaded NLCs hydrogel formulation assumes a pivotal role in bestowing sustained drug release and augmenting the antibacterial efficacy of carbapenem antibiotics. This holds promise as a potential solution to combat drug‐resistant bacterial infections.

Navigating the Nose-to-Brain Route: A Systematic Review on Lipid-Based Nanocarriers for Central Nervous System Disorders.

The blood-brain barrier (BBB) regulates brain substance entry, posing challenges for treating brain diseases. Traditional methods face limitations, leading to the exploration of non-invasive intranasal drug delivery. This approach exploits the direct nose-to-brain connection, overcoming BBB restrictions. Intranasal delivery enhances drug bioavailability, reduces dosage, and minimizes systemic side effects. Notably, lipid nanoparticles, such as solid lipid nanoparticles and nanostructured lipid carriers, offer advantages like improved stability and controlled release. Their nanoscale size facilitates efficient drug loading, enhancing solubility and bioavailability. Tailored lipid compositions enable optimal drug release, which is crucial for chronic brain diseases. This review assesses lipid nanoparticles in treating neuro-oncological and neurodegenerative conditions, providing insights for effective nose-to-brain drug delivery. A systematic search was conducted across major medical databases (PubMed, Ovid MEDLINE, and Scopus) up to 6 January 2024. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "lipid nanoparticles", "intranasal administration", "neuro-oncological diseases", and "neurodegenerative disorders". This review consists of studies in vitro, in vivo, or ex vivo on the intranasal administration of lipid-based nanocarriers for the treatment of brain diseases. Out of the initial 891 papers identified, 26 articles met the eligibility criteria after a rigorous analysis. The exclusion of 360 articles was due to reasons such as irrelevance, non-reporting selected outcomes, the article being a systematic literature review or meta-analysis, and lack of method/results details. This systematic literature review, focusing on nose-to-brain drug delivery via lipid-based nanocarriers for neuro-oncological, neurodegenerative, and other brain diseases, encompassed 60 studies. A temporal distribution analysis indicated a peak in research interest between 2018 and 2020 (28.3%), with a steady increase over time. Regarding drug categories, Alzheimer's disease was prominent (26.7%), followed by antiblastic drugs (25.0%). Among the 65 drugs investigated, Rivastigmine, Doxorubicin, and Carmustine were the most studied (5.0%), showcasing a diverse approach to neurological disorders. Notably, solid lipid nanoparticles (SLNs) were predominant (65.0%), followed by nanostructured lipid carriers (NLCs) (28.3%), highlighting their efficacy in intranasal drug delivery. Various lipids were employed, with glyceryl monostearate being prominent (20.0%), indicating preferences in formulation. Performance assessment assays were balanced, with in vivo studies taking precedence (43.3%), emphasizing the translation of findings to complex biological systems for potential clinical applications. This systematic review reveals the transformative potential of intranasal lipid nanoparticles in treating brain diseases, overcoming the BBB. Positive outcomes highlight the effectiveness of SLNs and NLCs, which are promising new approaches for ailments from AD to stroke and gliomas. While celebrating progress, addressing challenges like nanoparticle toxicity is also crucial.

Co-Delivery of siRNA and Docetaxel to Cancer Cells by NLC for Therapy.

The present study aims to develop a delivery system that can carry small interference RNA (siRNA) with small-molecule chemotherapeutic drugs, which can be used in cancer treatment. The drug delivery system combines the advantages of a therapeutic agent with two different mechanisms to ensure that it is used efficiently for cancer therapy. In this study, a nanostructured lipid carrier system was prepared, Docetaxel was loaded to these systems, and the Eph siRNA was adsorbed to the outer surface. In addition, DOTAP was added to the lipophilic phase to load a positive charge on the lipidic structure for interaction with the cells. Moreover, characterization, cytotoxicity, and transfection procedures were performed on the whole system. This candidate system was also compared to Taxotere, which is the first approved Docetaxel-containing drug on the market. Given the results, it was determined that the particle size of NLC-DTX was 165.3 ± 3.5 nm, the ζ potential value was 38.2 ± 1.7 mV, and the PDI was 0.187 ± 0.024. Entrapment efficacy of nanoparticles was found to be 92.89 ± 0.21%. It was determined that the lipidic system prepared in vitro release analyses were able to provide sustained release and exhibit cytotoxicity, even at doses lower than the dose used for Taxotere. The formulations prepared had a higher level of effect on cells when compared with pure DTX and Taxotere, but they also exhibited time-dependent cytotoxicity. It was also observed that the use of Eph siRNA together with the chemotherapeutic agent via formulation also contributed to this cell death. The results of the present study indicate that there is a promising carrier system in order to deliver hydrophilic nucleic acids, such as siRNA, together with lipophilic drugs in cancer treatment.

Impact of cocoa butter and medium chain triglycerides ratios on processing stability, supersaturation, and digestive properties of curcumin-loaded nanostructured lipid carriers

In the pursuit of optimal delivery of hydrophobic agents such as curcumin, the role of lipid composition in the efficacy of nanostructured lipid carriers is gaining significant attention. This study aimed to investigate the effects of cocoa butter (0–10 wt%) and medium chain triglycerides oil (0–10 wt%) mass ratios on processing stability, crystallization, polymorphism transition, supersaturation, encapsulation, and in vitro digestion of curcumin-loaded nanostructured lipid carriers (Cur-NLCs). Transmission electron microscopy (TEM) analysis showed that spherical Cur-NLCs exhibited larger average particle size with the increase in cocoa butter content. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) revealed that the crystallinity and thickness of solid shells decreased with the increase in liquid lipid content. The obtained Cur-NLCs remained stable under various conditions: thermal treatments (25, 37, 60, and 121 °C), varied ionic strengths (50–500 mM), pH changes (2.0–6.0), centrifugation (21382×g for 40 min), and 60-days storage. Furthermore, Cur-NLCs showed higher supersaturation (1863 ± 20–2328 ± 10%) than that of nanoemulsion (1489 ± 6%) and solid lipid nanoparticles (1635 ± 36%). In addition, the prepared Cur-NLCs exhibited high bioaccessibility (79.4 ± 3.1–91.1 ± 2.1%) along with a controlled release of curcumin. This study provides guidelines to prepare Cur-NLCs with tailored physicochemical, functional, and digestion properties to deliver hydrophobic bioactive substances, nutraceuticals, and pharmaceuticals.

A comprehensive review on alpha-lipoic acid delivery by nanoparticles.

Alpha-lipoic acid (ALA) has garnered significant attention for its potential therapeutic benefits across a wide spectrum of health conditions. Despite its remarkable antioxidant properties, ALA is hindered by challenges such as low bioavailability, short half-life, and unpleasant odor. To overcome these limitations and enhance ALA's therapeutic efficacy, various nanoparticulate drug delivery systems have been explored. This comprehensive review evaluates the application of different nanoparticulate carriers, including lipid-based nanoparticles (solid lipid nanoparticles, niosomes, liposomes, nanostructured lipid carriers (NLCs), and micelles), nanoemulsions, polymeric nanoparticles (nanocapsules, PEGylated nanoparticles, and polycaprolactone nanoparticles), films, nanofibers, and gold nanoparticles, for ALA delivery. Each nanoparticulate system offers unique advantages, such as improved stability, sustained release, enhanced bioavailability, and targeted delivery. For example, ALA-loaded SLNs demonstrated benefits for skin care products and skin rejuvenation. ALA encapsulated in niosomes showed potential for treating cerebral ischemia, a condition largely linked to stroke. ALA-loaded cationic nanoemulsions showed promise for ophthalmic applications, reducing vascular injuries, and corneal disorders. Coating liposomes with chitosan further enhanced stability and performance, promoting drug absorption through the skin. This review provides a comprehensive overview of the advancements in nanoparticulate delivery systems for ALA, highlighting their potential to overcome the limitations of ALA administration and significantly enhance its therapeutic effectiveness. These innovative approaches hold promise for the development of improved ALA-based treatments across a broad spectrum of health conditions.

Effect of Functional Groups in Lipid Molecules on the Stability of Nanostructured Lipid Carriers: Experimental and Computational Investigations.

Lipid nanoparticles have been used as drug carriers for decades. Many lipid types have been screened for both solid lipid nanoparticles and nanostructured lipid carriers (NLCs). Specifically, for NLCs that are composed of lipids in the solid form mixed with lipids in the liquid form, compatibility of lipid combination and phase behavior play a significant role in the NLC quality. In this study, stearic acid (STA) and cetyl palmitate (CTP) were used as solid lipids, and oleic acid (OLA), isopropyl palmitate (IPP), and caprylic/capric triglycerides were used as liquid lipids. NLCs were prepared at solid:liquid ratios of 50:50, 70:30, and 90:10, respectively. The characteristics and stability of the prepared NLCs were investigated. Laboratory results showed that the solid lipid had a greater influence on the particle size than the liquid lipid. Meanwhile, cetyl palmitate, an ester compound, provides higher NLC stability compared to stearic acid, a carboxylic acid compound. A MARTINI-based coarse-grained molecular dynamics simulation was used to simulate the lipid droplet in water. The distribution of lipid molecules in the droplet was characterized by the polar group density distribution. Different spatial arrangements of the lipid headgroup and lipid molecules, when CTP or STA was used as solid lipids, might contribute to the different stabilities of prepared NLCs. The understanding of mixed lipid systems via simulations will be a significant tool for screening the type of lipids for drug carriers and other pharmaceutical applications.

A Novel Strategy for Topical Administration by Combining Chitosan Hydrogel Beads with Nanostructured Lipid Carriers: Preparation, Characterization, and Evaluation.

The objective of the present study was to develop and evaluate NLC-chitosan hydrogel beads for topical administration. The feasibility of the preparation technology was verified by investigating various formulation factors and the impact of chitosan hydrogel beads on the NLC. The encapsulation efficiency of NLC-chitosan hydrogel beads was above 95% in optimized process conditions. The physical characterization of the NLC-chitosan hydrogel beads showed that the NLC was distributed within the network of the chitosan hydrogel beads. Furthermore, the incorporation of NLC into the chitosan hydrogel beads was related to the electrostatic interaction between the surface of the NLC and chitosan, which influenced the lipid ordering degree of the NLC and contributed to the stability. The stability studies showed that the retention rate of quercetin in the NLC-chitosan hydrogel beads was 88.63 ± 2.57% after 10 months of storage under natural daylight. An in vitro permeation study showed that NLC-chitosan hydrogel beads exhibited superior ability in enhancing skin permeation by hydrophobic active ingredients compared to the NLC and significantly increased skin accumulation. These studies demonstrated that the use of NLC-chitosan hydrogel beads might be a promising strategy for the delivery of hydrophobic active ingredients in topical administration.

REVIEW: REVIEW ARTICLE LIPID-BASED NANOTECHNOLOGY

Nanotechnology is defined as engineering the creation of materials, functions, and devices on the nanometer scale. Nanoscience is increasingly developing and becoming a part of various fields, such as electronics, materials, and biology. Lipid nanoparticles are a major application in nanotechnology. In formulas II and III, smaller results were obtained compared with the other formulas. Based on the results of this study, it can be concluded that the nanostructured lipid carrier system with solid lipid poloxamer and stearic acid with liquid soybean oil lipids obtained good characteristics, and each test met the range. From the explanation above, it can be concluded that lipid-based nanotechnology has great potential in various fields such as medicine, cosmetics, and agriculture. Its use can provide great benefits such as increasing the effectiveness of drug administration, increasing the absorption of nutrients in food, and developing cosmetic products. which one is safer and more effective. To compare several types of nanoparticle methods, such as Liposomes, Neosomes, Etosomes, SLN, and NLC for selection of the lipid base, namely NLC. It is important to ensure that the use and development of this technology are safe and beneficial for humans and the environment. Keywords : Nanotechnology, Nanoparticles, Lipid-Based Nanoparticles

Integrating Nanotechnological Advancements of Disease-Modifying Anti-Rheumatic Drugs into Rheumatoid Arthritis Management.

Disease-modifying anti-rheumatic drugs (DMARDs) is a class of anti-rheumatic medicines that are frequently prescribed to patients suffering from rheumatoid arthritis (RA). Methotrexate, sulfasalazine, hydroxychloroquine, and azathioprine are examples of non-biologic DMARDs that are being used for alleviating pain and preventing disease progression. Biologic DMARDs (bDMARDs) like infliximab, rituximab, etanercept, adalimumab, tocilizumab, certolizumab pegol, and abatacept have greater effectiveness with fewer adverse effects in comparison to non-biologic DMARDs. This review article delineates the classification of DMARDs and their characteristic attributes. The poor aqueous solubility or permeability causes the limited oral bioavailability of synthetic DMARDs, while the high molecular weights along with the bulky structures of bDMARDs have posed few obstacles in their drug delivery and need to be addressed through the development of nanoformulations like cubosomes, nanospheres, nanoemulsions, solid lipid nanoparticles, nanomicelles, liposome, niosomes, and nanostructured lipid carrier. The main focus of this review article is to highlight the potential role of nanotechnology in the drug delivery of DMARDs for increasing solubility, dissolution, and bioavailability for the improved management of RA. This article also focusses on the different aspects of nanoparticles like their applications in biologics, biocompatibility, body clearance, scalability, drug loading, and stability issues.

Nanoformulated meloxicam and rifampin: inhibiting quorum sensing and biofilm formation in Pseudomonas aeruginosa.

Background: We aimed to investigate the simultaneous effects of meloxicam and rifampin nanoformulations with solid lipid nanoparticle (SLN) and nanostructured lipid carrier (NLC) substrates on inhibiting the quorum-sensing system of Pseudomonas aeruginosa and preventing biofilm formation by this bacterium. Methods: Antimicrobial activity of rifampin and meloxicam encapsulated with SLNs and NLCs against P. aeruginosa PAO1 was assessed by disk diffusion, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Results: The SLN formulation was associated with lower doses for the MIC and minimum bactericidal concentration in comparison to NLC. Moreover, our results demonstrated that both nanoformulations were able to produce 100% inhibition of the biofilm formation of P. aeruginosa PAO1. Conclusion: All these findings suggest that meloxicam and rifampin encapsulated with SLNs could be the most effective formulation against P. aeruginosa.

Small-angle X-ray scattering unveils the internal structure of lipid nanoparticles

Lipid nanoparticles own a remarkable potential in nanomedicine, only partially disclosed. While the clinical use of liposomes and cationic lipid-nucleic acid complexes is well-established, liquid lipid nanoparticles (nanoemulsions), solid lipid nanoparticles, and nanostructured lipid carriers have even greater possibilities. However, they face obstacles in being used in clinics due to a lack of understanding about the molecular mechanisms controlling their drug loading and release, interactions with the biological environment (such as the protein corona), and shelf-life stability. To create effective drug delivery carriers and successfully translate bench research to clinical settings, it is crucial to have a thorough understanding of the internal structure of lipid nanoparticles. Through synchrotron small-angle X-ray scattering experiments, we determined the spatial distribution and internal structure of the nanoparticles' lipid, surfactant, and the bound water in them. The nanoparticles themselves have a barrel-like shape that consists of coplanar lipid platelets (specifically cetyl palmitate) that are covered by loosely spaced polysorbate 80 surfactant molecules, whose polar heads retain a large amount of bound water. To reduce the interface cost of bound water with unbound water without stacking, the platelets collapse onto each other. This internal structure challenges the classical core-shell model typically used to describe solid lipid nanoparticles and could play a significant role in drug loading and release, biological fluid interaction, and nanoparticle stability, making our findings valuable for the rational design of lipid-based nanoparticles.

Ezetimibe-Loaded Nanostructured Lipid Carrier for Oral Delivery: Response Surface Methodology; In Vitro Characterization and Assessing the Antihyperlipidemic Effect in Rats.

Among the independent risk factors for the occurrence of cardiovascular diseases like atherosclerosis is hyperlipidemia. To decrease cardiovascular events and patient mortality, antihyperlipidemia therapy is crucial. Our study aimed to enhance the solubility of the poorly soluble lipid-lowering agent ezetimibe (EZ), a member of class II as per the Biopharmaceutics Classification System (BCS). The drug was formulated as a nanostructured lipid carrier (NLC) employing the ultrasonication technique. A response surface D-optimal design was employed to study the effect of changing the liquid lipid type and the percentage of liquid lipid with respect to total lipid amount on the particle size, zeta potential, percentage entrapment efficiency, and percentage of drug released after 24 h. Nine NLC formulations were prepared and pharmaceutically evaluated, and the optimized NLC formulation was selected, further characterized, and evaluated as well. Optimized EZ-NLC was assessed in the high-fat diet model to induce hyperlipidemia in rats in comparison with the EZ suspension. The results of the optimized formulation showed that the prepared NLCs were spherical with no aggregation having a particle size of 204.3 ± 19.17 nm, zeta potential equal to -32 ± 7.59 mV, and entrapment efficiency of 81.5 ± 3.58% and 72.15 ± 4.58% drug released after 24 h. EZ-NLC significantly decreased the elevated serum lipid parameters, including total cholesterol, triglycerides, and LDL-C, but significantly normalized serum HDL-C levels of rats kept on a high-fat diet. The results demonstrated the improved efficacy of EZ-NLC in ameliorating the elevated serum lipid parameters compared to EZ.

Comprehensive strategy of white analytical chemistry and analytical quality by design to sensitive spectrofluorimetric method for in-vitro drug release kinetic study of Ibrutinib-loaded nanostructured lipid carriers for leukemia via lymphatic targeting

Ibrutinib (IBR) is a drug classified as BCS class II, characterized by low solubility and high permeability. However, its oral bioavailability is limited to a mere 2.9% due to significant first-pass metabolism. To address this challenge, researchers developed IBR-NLCs (Nanostructured Lipid Carriers) using a DoE-based hot melted ultrasonication method to enhance its bioavailability and drug release profile. While various methods exist for IBR analysis in pharmaceutical formulations, human plasma, and rat plasma, a sensitive spectrofluorimetric method has not been reported for estimating IBR. To facilitate in-vitro drug release kinetic studies of IBR-NLCs, a sensitive and green spectrofluorimetric method was developed, combining principles of white analytical chemistry and analytical quality by design. This approach included a fractional factorial design for screening of method variables and a Box-Behnken design for method optimization. The developed method underwent rigorous validation following ICH guidelines. The developed method was applied to assess the in-vitro drug release kinetic study of IBR-NLCs in comparison to marketed formulations. Remarkably, the optimized IBR-NLCs exhibited sustained release of IBR which helps to decrease dose and dose frequency. The whiteness and greenness profiles of published and proposed method have been assessed using analytical greenness calculator, green analytical procedure index software, national environmental method index standards, and eco-scale assessment tool. The results confirmed that the proposed method is sensitive, eco-friendly, cost-effective, speedy, and user-friendly, making it an excellent choice for IBR estimation in NLCs. In summary, the developed method for drug release kinetic study of BR-NLCs, utilizing principles of white analytical chemistry and analytical quality by design, has not only improved drug release profile but also resulted in an efficient and environmentally friendly analytical approach.

Optimized Ribociclib nanostructured lipid carrier for the amelioration of skin cancer: Inferences from ex-vivo skin permeation and dermatokinetic studies

Current research focuses on explicitly developing and evaluating nanostructured lipidic carriers (NLCs) for the chemotherapeutic drug Ribociclib (RCB) via the topical route to surmount the inherent bioavailability shortcomings. The absolute oral bioavailability has not been determined, but using a physiologically based pharmacokinetic model it was predicted that 65.8 % of the standard dose of RCB (600 mg) would be absorbed mainly in the small intestine. RCB-NLCs were produced using the solvent evaporation method, and Box-Behnken Design (BBD) was employed to optimize composition. The prepared NLCs had an average PS of 79.29 ± 3.53 nm, PDI of 0.242 ± 0.021, and a %EE of 86.07 ± 3.14. The TEM analysis disclosed the spherical form and non-aggregative nature of the NLCs. The outcomes of an in-vitro release investigation presented cumulative drug release of 84.97 ± 3.37 % in 24 h, significantly higher than that from the RCB suspension (RCB-SUS). Ex-vivo skin permeation investigations on rodent (Swiss albino mice) revealed that RCB-NLCs have 1.91 times increases in skin permeability comparable to RCB-SUS. Compared to RCB-SUS, RCB-NLCs were able to penetrate deeper into the epidermis membrane than RCB-SUS as per the findings of confocal microscopy. In dermatokinetic study, higher amount of RCB was maintained in both the layers of mice's skin when treated with RCB-NLCs gel comparable to the RCB-SUS gel preparation. The in-vitro, ex-vivo, CLSM, and dermatokinetics data demonstrated a significant possibility for this novel RCB formulation to be effective against skin cancer.