Solid Lipid Nanoparticles Research Articles

Guiding Therapeutics: Lipid Labyrinths and Nanostructures for Enhanced Drug Delivery

Abstract: Nanostructured lipid carriers (NLCs) offer a breakthrough platform for drug therapy, surpassing traditional limitations and delivering exceptional performance. Among various nanoparticulate systems, lipid nanoparticles stand out as one of the most promising options for medication delivery. NLCs stand out due to their solid matrix at ambient temperatures, setting them apart from conventional lipid-based carriers such as nanoemulsions and solid lipid nanoparticles. This paper thoroughly explores the makeup, classification, components, and various methods of preparing NLCs, based on extensive research findings. It emphasizes their numerous advantages, such as improved stability, minimal toxicity, extended storage capability, increased drug-loading capacity, and compatibility with biological systems. The review provides insights into the advantages and limitations of each method. Exploring the intricacies of drug loading and release, the review also addresses strategies to bolster NLCs’ stability. Moreover, it provides a detailed summary of both laboratory- based and animal studies demonstrating the efficacy of NLCs carrying cytotoxic drugs, particularly emphasizing their promise in targeted drug delivery to the brain. As the next-generation lipid nanocarriers, NLCs are composed of physiological and biocompatible lipids, rendering them novel pharmaceutical formulations. These colloidal drug delivery systems boast a solid lipid matrix with nanosized structures, offering superior drug loading capacity, physical stability, and bioavailability compared to conventional lipid nanoparticles. Several techniques, including high-pressure homogenization, microemulsion, solvent evaporation, and melt emulsification, add to the flexibility of nanostructured lipid carriers. Additionally, their exterior can be altered using coatings such as polyethylene glycol, chitosan, or antibodies to improve targeting ability and stealth characteristics. By elucidating the promising role of NLCs across diverse drug delivery systems, this review stimulates interest in their potential applications. It underscores the significance of understanding the structure, content, multiple formulation procedures, and characterization of NLCs, which are pivotal aspects for establishing stable drug delivery systems.

Lipid-Based Nanoparticles as Drug Delivery System for Modern Therapeutics.

The emergence of lipid-based nanoparticulate systems has significantly reshaped the landscape of drug delivery. This review aims to encapsulate the advancements, challenges, and potential of lipid-based nanoparticulate drug delivery in modern therapeutics. Lipid-based nanoparticles, including liposomes, lipid nanoparticles, and solid lipid nanoparticles, harness the biocompatibility and biodegradability of lipids to encapsulate and deliver a diverse range of therapeutic agents. This platform offers solutions to various drug delivery challenges, such as enhancing drug solubility and bio- availability, achieving controlled and sustained release, targeted delivery, and co-delivery of multi-agents. These nanoparticles have demonstrated potential in overcoming biological barriers, including the blood-brain barrier, mucosal barriers, and cellular barriers, enabling the delivery of drugs to previously inaccessible sites. Biocompatibility and reduced toxicity are intrinsic attributes of lipid-based nanoparticles, minimizing immune responses and systemic toxicity while promoting personalized medicine possibilities. However, challenges in formulation, stability, and regulatory approval underscore the need for ongoing research and innovation in this field.

New Insight for Enhanced Topical Targeting of Caffeine for Effective Cellulite Treatment: In Vitro Characterization, Permeation Studies, and Histological Evaluation in Rats

Cellulite (CLT) is one of the commonly known lipodystrophy syndromes affecting post-adolescent women worldwide. It is topographically characterized by an orange-peel, dimpled skin appearance hence, it is an unacceptable cosmetic problem. CLT can be modulated by surgical procedures such as; liposuction and mesotherapy. But, these options are invasive, expensive and risky. For these reasons, topical CLT treatments are more preferred. Caffeine (CA), is a natural alkaloid that is well-known for its prominent anti-cellulite effects. However, its hydrophilicity hinders its cutaneous permeation. Therefore, in the present study CA was loaded into solid lipid nanoparticles (SLNs) by high shear homogenization/ultrasonication. CA-SLNs were prepared using Compritol® 888 ATO and stearic acid as solid lipids, and span 60 and brij™35, as lipid dispersion stabilizing agents. Formulation variables were adjusted to obtain entrapment efficiency (EE > 75%), particle size (PS < 350 nm), zeta potential (ZP < −25 mV) and polydispersity index (PDI < 0.5). CA-SLN-4 was selected and showed maximized EE (92.03 ± 0.16%), minimized PS (232.7 ± 1.90 nm), and optimum ZP (−25.15 ± 0.65 mV) and PDI values (0.24 ± 0.02). CA-SLN-4 showed superior CA release (99.44 ± 0.36%) compared to the rest CA-SLNs at 1 h. TEM analysis showed spherical, nanosized CA-SLN-4 vesicles. Con-LSM analysis showed successful CA-SLN-4 permeation transepidermally and via shunt diffusion. CA-SLN-4 incorporated into Noveon AA−1® hydrogel (CA-SLN-Ngel) showed accepted physical/rheological properties, and in vitro release profile. Histological studies showed that CA-SLN-Ngel significantly reduced mean subcutaneous fat tissue (SFT) thickness with 4.66 fold (p = 0.035) and 4.16 fold (p = 0.0001) compared to CA-gel, at 7th and 21st days, respectively. Also, significant mean SFT thickness reduction was observed compared to untreated group with 4.83 fold (p = 0.0005) and 3.83 fold (p = 0.0043), at 7th and 21st days, respectively. This study opened new avenue for CA skin delivery via advocating the importance of skin appendages. Hence, CA-SLN-Ngel could be a promising nanocosmeceutical gel for effective CLT treatment.Graphical

Emerging Nanoparticle-Based Herbal Drug Delivery Systems for Colon Targeting Therapy

Abstract: Herbal medications hold a dominant position in the pharmaceutical sector due to their well-established therapeutic effects and extremely low negative effects. Besides, herbal remedies are easily available and highly economical. However, to circumvent the issue of poor bioavailability, the combinatorial strategy of incorporating herbal medicines and nano-technology is useful. The phytoconstituents molded in novel nanocarriers such as polymeric nanoparticles, polymeric micelles, liposomes, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, gold nanoparticles, etc., have been extensively investigated as they are the most promising approach for colon-targeting drug delivery systems. Although plant-based medicines have been developed for decades, there is enormous research interest in the development of an effective plant-derived delivery system for the incorporation of phytocon-stituents into various nanomaterials to overcome potential challenges related to solubility, bioavailability, and stability issues. The encapsulation of phytoconstituents in a novel nanocarrier is a promising approach to improving the bioavailability, stability, and therapeutic efficacy of herbal medicines. The herbal nanomedicines are used as a promising tool for tar-geted delivery to the colon, with potentially effective outcomes for the treatment of colonic diseases, viz., ulcerative colitis, diverticulitis, Crohn's disease, shigellosis, constipation, co-lonic polyps, colon cancer, etc. This article presents a comprehensive survey of recent find-ings and patents by innovators working exclusively on nanoparticles for the delivery of phy-tomedicines for colon targeting.

How do various encapsulation techniques improve the oral delivery of food protein hydrolysates?

AbstractThe development of bioformulations based on food protein hydrolysates (FPHs) has gained significant traction in the food and pharmaceutical sectors due to their biophysical and biochemical properties, including health‐promoting effects, biocompatibility, and biodegradability. However, the oral delivery of FPHs presents notable technical challenges, largely due to their inherent limitations such as (bio)stability, permeability, bioavailability, and molecular size. This review provides a comprehensive overview of FPHs, including their structural characteristics, origins, methods of preparation, and associated health benefits. Additionally, it highlights the challenges related to their oral delivery. Recent advancements in the formulation and delivery of FPHs through biopolymeric controlled release systems—such as micro‐ and nanoparticles, hydrogels, biofunctional films and composites, and electrospun fibers—are discussed. We also explore lipid‐based delivery platforms, including liposomes, chitosomes, emulsions, Pickering emulsions, nanostructured lipid carriers, solid lipid nanoparticles, and surfactant‐based carriers. Furthermore, this article emphasizes the importance of controlled delivery and targeted release of FPHs following oral administration. The challenges in designing effective lipid/biopolymer‐based carriers for FPHs, along with future prospects and opportunities in this growing field, are also thoroughly examined.

Solid Lipid Nanoparticles, an Alternative for the Treatment of Triple-Negative Breast Cancer

Within the field of nanomedicine, which is revolutionizing cancer treatment, solid lipid nanoparticles (SLNs) have shown advantages over conventional chemotherapy when tested on cancer cells in preclinical studies. SLNs have proven to be an innovative strategy for the treatment of triple-negative breast cancer cells, providing greater efficiency than existing treatments in various studies. The encapsulation of antineoplastic drugs in SLNs has facilitated a sustained, controlled, and targeted release, which enhances therapeutic efficiency and reduces adverse effects. Moreover, the surface of SLNs can be modified to increase efficiency. For instance, the coating of these particles with polyethylene glycol (PEG) decreases their opsonization, resulting in a longer life in the circulatory system. The creation of positively charged cationic SLNs (cSLNs), achieved by the utilization of surfactants or ionic lipids with positively charged structural groups, increases their affinity for cell membranes and plasma proteins. Hyaluronic acid has been added to SLNs so that the distinct pH of tumor cells would stimulate the release of the drug and/or genetic material. The current review summarizes the recent research on SLNs, focusing on the encapsulation and transport of therapeutic agents with a cytotoxic effect on triple-negative breast cancer.

Enhancing Acute Migraine Treatment: Exploring Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for the Nose-to-Brain Route.

Migraine has a high prevalence worldwide and is one of the main disabling neurological diseases in individuals under the age of 50. In general, treatment includes the use of oral analgesics or non-steroidal anti-inflammatory drugs (NSAIDs) for mild attacks, and, for moderate or severe attacks, triptans or 5-HT1B/1D receptor agonists. However, the administration of antimigraine drugs in conventional oral pharmaceutical dosage forms is a challenge, since many molecules have difficulty crossing the blood-brain barrier (BBB) to reach the brain, which leads to bioavailability problems. Efforts have been made to find alternative delivery systems and/or routes for antimigraine drugs. In vivo studies have shown that it is possible to administer drugs directly into the brain via the intranasal (IN) or the nose-to-brain route, thus avoiding the need for the molecules to cross the BBB. In this field, the use of lipid nanoparticles, in particular solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), has shown promising results, since they have several advantages for drugs administered via the IN route, including increased absorption and reduced enzymatic degradation, improving bioavailability. Furthermore, SLN and NLC are capable of co-encapsulating drugs, promoting their simultaneous delivery to the site of therapeutic action, which can be a promising approach for the acute migraine treatment. This review highlights the potential of using SLN and NLC to improve the treatment of acute migraine via the nose-to-brain route. First sections describe the pathophysiology and the currently available pharmacological treatment for acute migraine, followed by an outline of the mechanisms underlying the nose-to-brain route. Afterwards, the main features of SLN and NLC and the most recent in vivo studies investigating the use of these nanoparticles for the treatment of acute migraine are presented.

Physicochemical and biological characterization of the lipid particles with bovine serum albumin corona

Diacylglycerol–based nanoparticles are promising bioactive delivery systems. However, limited understanding of their interaction with biological entities restricts their clinical use. This study investigated the protein corona formed on medium and long chain diacylglycerol (MLCD)-based solid lipid nanoparticles (NPs) modified by Polyoxethylene stearate (PEG) and compared to glyceryl tristearate (TG) and cetyl palmitate (CP) nanoparticles. Bovine serum albumin (BSA) formed corona with MLCD NPs through hydrophobic interactions and hydrogen bonding, contributing to a decrease in α–helix, an increase in β–sheet and a change in the microenvironment of Tyr residues. Owing to higher lipid hydrophilicity, MLCD NPs showed a much lower affinity for BSA than TG and CP NPs, and the binding constant with BSA was increased for larger NPs. PEG modification and the protein corona reduced the uptake of NPs by macrophages but exerted little influence on B16 cell. Among the NPs with different lipid core, the MLCD NPs showed a lower macrophages cell uptake but higher B16 cell uptake, suggesting a longer circulation time in blood but higher cancer cell internalization. This work shed light on the interactions between MLCD NPs and proteins, which is significant for application as nanocarriers with improved biological efficacy.

Betulin-NLC-hydrogel for the Treatment of Psoriasis-like Skin Inflammation: Optimization, Characterisation, and In vitro and In vivo Evaluation.

Psoriasis is a chronic inflammatory skin disorder that poses significant challenges regarding effective and targeted drug delivery. Bioactive substances like betulin have shown tremendous utility in treating these conditions; however, they pose limited utility owing to their physicochemical characteristics. Here, we aimed to develop a novel topical dosage form for treating psoriasis, utilising betulin-loaded solid lipid nanoparticles (NLCs) incorporated into a hydrogel matrix. The optimization of the formulation was meticulously conducted using a design of experiments methodology, and its diverse physicochemical attributes were thoroughly examined. Evaluating betulin's in vitro release pattern from the NLC-hydrogel demonstrated consistent and regulated drug release properties. Additionally, the formulation demonstrated improved skin penetration abilities as determined by in vitro skin permeation experiments employing Franz diffusion cells- furthermore, the therapeutic effectiveness of the betulin-NLC-hydrogel was assessed by an in vivo experiment carried out using an imiquimod-induced psoriasis-like skin inflammation model in BALB/c female mice. The NLCs exhibited a pH of 5.67±0.86, particle size of 148.16±12.66 nm, and zeta potential of -22.84±2.37 mV, ensuring stability and suitability for topical use. The gel, with a pH of 6.05±0.43 and viscosity of 17550±120 cPs, showed enhanced skin hydration and lipid restoration. Drug release studies indicated a slower release from NLCs and gel, improving skin retention. Stability tests revealed that the formulations were stable at room temperature but not at elevated temperatures. The in vitro safety profile of the formulation revealed no significant adverse effects on HaCaT cell lines. The NLC gel demonstrated significant anti-psoriatic activity, reducing inflammation and cytokine levels. The betulin-NLC-hydrogel formulation exhibited promising characteristics for the topical treatment of psoriasis, showcasing optimised drug delivery, sustained release, and notable therapeutic efficacy. The findings from this study provide a foundation for the potential clinical translation of this innovative topical dosage form for improved psoriasis management.

Are Nanostructured Lipid Carriers (NLC) better than Solid Lipid Nanoparticles (SLN) for delivering abiraterone acetate through the gastrointestinal tract?

Abiraterone acetate (AbA) is a progesterone derivative indicated for the treatment of metastatic prostate cancer. This BCS (Biopharmaceutics Classification System) Class IV molecule has an extremely poor oral bioavailability (<10 %), notably due to its very low water solubility and intestinal permeability. Among the few existing galenic strategies to improve AbA’s oral bioavailability, lipid nanoparticles such as Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) are relevant nanovectors. The objective of this study is to develop and compare SLN and NLC for oral delivery of abiraterone acetate. Both SLN and NLC are biocompatible, biodegradable and produced by high pressure homogenization (HPH), an ecological-friendly manufacturing process, organic solvent-free and easily scalable. The HPH process allowed the formation of AbA-loaded SLN and NLC with particle size lower than 160 nm and high encapsulation efficiencies. The addition of a liquid lipid significantly reduced the mean diameter of the nanoparticles, reflecting the greater benefit of the NLC formulation compared to SLN. Both SLN and NLC formulations offered an important protection of AbA in intestinal media, with a better stability for NLC. When encapsulated in SLN or NLC, the AbA is strongly retained by the nanoparticles, whatever the dissolution medium, which means that both formulas are able to protect and retain the drug in the intestinal tract, right up to its delivery to the enterocytes surface. High concentrations of nanoparticles were administered without cytotoxicity, especially for the NLC, which provides a real added value in terms of biocompatibility with Caco-2 cells. Finally, the nanoparticles were able to penetrate into enterocytes by the transcellular route, demonstrating an intense cellular internalization.

Prolonged Skin Retention of Luliconazole from SLNs Based Topical Gel Formulation Contributing to Ameliorated Antifungal Activity.

The development of effective therapy is necessary because the patients have to contend with long-termtherapy as skin fungal infections usually relapse and are hardly treated. Despite being a potent antifungal agent, luliconazole (LCZ) has certainshortcomings such as limited skin penetration, low solubility in aqueous medium, and poor skin retention. Solid Lipid Nanoparticles (SLNs) were developed using biodegradable lipids by solvent injection method and were embodied into the gel base for topical administration. After in-vitro characterizations of the formulations, molecular interactions of the drug with excipients were analyzed using in-silico studies. Ex-vivo release was determined in contrast to the pure LCZ and the commercial formulation followed by in-vivo skin localization, skin irritation index, and antifungal activity. The prepared SLNs have an average particle size of 290.7nm with no aggregation of particles and homogenous gels containing SLNs with ideal rheology and smooth texture properties were successfully prepared. The ex-vivo LCZ release from the SLN gel was lower than the commercial formulation whereas its skin deposition and skin retention were higher as accessed by CLSM studies. The drug reaching the systemic circulation and the skin irritation potential were found to be negligible. Thesolubility and drug retention in the skin were both enhanced by the development of SLNs as a carrier. Thus, SLNs offer significant advantages by delivering long lasting concentrations of LCZ at the site of infection for a complete cure of the fungal load together with skin localization of the topical antifungal drug.

Formulation Optimization and Evaluation of Patented Solid Lipid Nanoparticles of Ambrisentan for Pulmonary Arterial Hypertension.

Ambrisentan is a new endothelin receptor antagonist extensively used to manage pulmonary or pulmonary arterial hypertension. The therapeutic efficacy of Ambrisentan is limited due to its reduced solubility, higher log P (3.4), and thus less bioavailability. The recent investigation was concentrated on the improvement of solubility, and bioavailability of Ambrisentan for the therapy of hypertension via solid lipid nanoparticles (SLN) administered orally. XRD evaluated the compatibility of Ambrisentan with lipids with FTIR, DSC, and crystalline nature. The SLN was developed by High-pressure homogenization method. The Glyceryl monostearate and Tween 80 indicated the highest solubility, hence selected. The optimization was performed with Box-Behnken Design considering the concentration of GMS (X1), Tween 80 (X2), stirring speed (X3) as independent factors and particle size (Y1), entrapment efficiency (Y2) as dependent factors. The Patents on the SLN are Indian 202321053691, U.S. Patent, 10,973,798B2, U.S. Patent 10,251,960B2, U.S. Patent 2021/0069121A1 and U.S. Patent 2022/0151945A1. The optimized batch F1 showed particle size (130 nm), ZP (-18.9 mV), and entrapment efficiency (85.73 %). The dual release pattern (prompt and sustained) was achieved with the SLNloaded Ambrisentan for about 24 hours. The lyophilized sample was subjected to SEM, which also revealed a spherical shape of a colloidal dispersion with a particle size of 126 nm. Hence, the F1 batch is highly recommended for solid oral delivery and also for the pilot-plant scale-up. A marked improvement in the solubility and dissolution of Ambrisentan was attained with the SLN. Moreover, the sustained delivery via the oral route enabled the patient's comfort, compliance, and therapeutic efficacy.

Establishment of a semi-continuous nano-production line using the Microfluidizer® technology for the fabrication of lipid-based nanoparticles part 1: Screening of critical parameters and Design of Experiment optimization studies

A variety of strategies for producing high-quality nanoparticles have been reported in recent years. Batch-based bottom-up and top-down technologies are generally the most efficient methods, but present a number of challenges, particularly in terms of variability, safety, sustainability and large-scale production. In this study, a scalable, semi-continuous production line was built by connecting individual processing units, including a high shear mixing device, the Microfluidizer® technology and a cooling system. Each unit was equipped with an adequate temperature control to allow solvent-free production of solid lipid nanoparticles (consisting of Precirol® ATO 5 or Gelucire® 43/01) and nanostructured lipid carriers (additionally comprising Labrafac™ lipophile WL 1349). Subsequently, critical formulation parameters and critical process parameters (CPPs) of the individual processing units and their effects on particle size (i.e., critical quality attribute (CQA)) were investigated to identify appropriate input parameters for the subsequent Design of Experiment (DoE) studies conducted after linking the process units to a semi-continuous production line. For particle size monitoring, spatially resolved dynamic light scattering (SR-DLS) measurements were conducted and compared to standard DLS measurements to evaluate the applicability of SR-DLS as an inline monitoring tool. It was found that matrix composition, emulsifier concentration, pressure and number of cycles when processing through Microfluidizer® processor were the most influencing parameters. By optimizing these parameters, five-times higher throughputs could be achieved by the semi-continuous manufacturing line. In addition, the particle size measurements with SR-DLS confirmed the feasibility of implementing this technology for real-time particle size monitoring as an important safety factor in quality control.

Oral delivery of solid lipid nanoparticles surface decorated with hyaluronic acid and bovine serum albumin: A novel approach to treat colon cancer through active targeting

The present study aims to prepare and evaluate solid lipid nanoparticles (SLNs) loaded with irinotecan (IRN) drug and daidzein (DZN) isoflavonoid and surface coated with ligand materials such as hyaluronic acid (HA) and bovine serum albumin (BSA) with additional coating of chitosan for active targeting to receptors present on colon surface epithelium for oral targeted delivery. The optimized batch was evaluated for particle size, zeta potential exhibiting nanometric size with good entrapment efficiency. Nanoparticles were found to be spherical. FTIR and DSC revealed that all the excipients and formulation were compatabile to each other and showed better encapsulation exhibiting amorphous and crystallinity forms. In vitro drug release of SLNs confirmed that initially a burst release, followed by sustained release pattern was exhibited. Cell lines studied performed on HT-29 cells showed demonstrated that conjugated SLNs inhibited cytotoxicity at 75 μg/ml, indicating that cells were taken up through a receptor-mediated endocytosis process. Cell cycle analysis showed that cell arrest was done at 67.8 % (G0/G1 phase) and inhibited apoptosis by 56 %. Further during In vivo studies, RT-PCR study revealed downregulation of Carcinoembryonic antigen (CEA), a non-specific serum biomarker overexpressed in tumor cells and upregulation of pro-inflammatory cytokine TNF-α. Histopathological study revealed that conjugated (HA-BSA) coated with chitosan SLNs restored normal mucosa and colon architecture, depicting all mucosal layers. Hence, these conjugated SLNs may serve as a novel combination for the treatment of colon cancer.

In Vitro Cytotoxicity and Pharmacokinetic Study for Bosutinib Solid Lipid Nanoparticles.

Bosutinib (BST) is a Biopharmaceutics Classification System Class II drug having very low solubility and high permeability. Low aqueous solubility and poor dissolution of BST lead to poor bioavailability, Thus, limited aqueous solubility is the bottleneck for the therapeutic outcome of BST. Animal data suggest that the absolute bioavailability of BST is about 14-34% due to an extensive first-pass effect. To overcome hepatic first-pass metabolism and to enhance oral bioavailability, lipid-based drug delivery systems such as solid lipid nanoparticles (SLNs) can be used. SLNs are submicron colloidal carriers having a size range of 50-1000 nm. These are prepared with physiological lipid and dispersed in water or aqueous surfactant solution. BST can be conveniently loaded into SLNs to improve the oral bioavailability by exploiting the intestinal lymphatic transport. An optimal system was evaluated for bioavailability study in rats compared with that of BST suspension (SUS). An in vitro cytotoxicity study was done by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay method through ATCC cell lines; the percent inhibition was more in SLN when compared with SUS. The pharmacokinetics of BST-SLNs after oral administration in male Wistar rats was studied. The bioavailability of BST was increased by 2.28 fold when compared with that of a BST SUS. The results are indicative of SLNs as suitable lipid-based carrier system for improving the oral bioavailability of BST.

4-Hexylresorcinol Loaded Solid Lipid Nanoparticles for Enhancing Anticancer Activity.

Cancer is one of the most significant threats to human health. Following surgical excision, chemotherapy is an effective strategy against remaining cancer cells. 4-hexylresorcinol (4-HR) has anti-cancer properties and exhibits hydrophobicity-induced aggregation in the blood that has trouble with targeted tumor delivery and cellular uptake of the drug. The purpose of this study is to encapsulate 4-HR into solid lipid nanoparticles (SLNs) to enhance its anti-cancer effect by avoiding aggregation and facilitating cellular uptake. 4-HR SLNs were prepared via hot melt homogenization with sonication. SLN characteristics were assessed by analyzing particle size, zeta potential, and drug release. Cytotoxicity, as an indicator of the anti-cancer effect, was evaluated against HeLa (cervical cancer in humans), A549 (lung cancer in humans), and CT-26 (colon carcinoma in mice) cell lines. Particle size ranged from 169.4 to 644.8 nm, and zeta potential ranged from -19.8 to -40.3 mV, which are conducive to cellular uptake. Entrapment efficiency (EE) of 4-HR was found to be 75.0-96.5%. The cytotoxicity of 4-HR-loaded SLNs demonstrated enhanced anti-cancer effects compared to pure 4-HR. The enhancement of anti-cancer effects depended on reduced particle size based on cellular uptake, the EE, and the cell type. These findings imply that 4-HR-loaded SLN is a promising strategy for chemotherapy in cancer treatment.

“Formulation and Evaluation of Solid Lipid Nanoparticles by using High-Pressure Homogenization Technique for the Treatment of Cancer”

“Formulation and Evaluation of Solid Lipid Nanoparticles by using High-Pressure Homogenization Technique for the Treatment of Cancer”

SLNs and NLCs for Skin Applications: Enhancing the Bioavailability of Natural Bioactives.

Natural bioactives are mixtures of compounds extracted from plants with physicochemical properties that are usually not favorable for penetrating the skin's complex barrier. Nanoparticles have important advantages both in dermatology and cosmetology: improved solubility and stability of encapsulated phytocompounds, controlled and sustained skin delivery, and enhanced skin permeation, leading to an improved bioavailability. This review focuses on two generations of lipid-based nanoparticles: solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). An extensive overview on the recent studies on SLNs and NLCs entrapping essential oils, oils, herbal extracts, and phytocompounds for topical applications is presented, emphasizing their composition, physicochemical characterization, efficacy, and methodologies used to evaluate them. This review also summarizes topical systems containing natural bioactives incorporated into SLNs and NLCs, commercially available products and registered patents in the field. SLNs and NLCs turn out to be effective nanocarriers for skin applications, offering significantly improved encapsulation efficiency, stability, and bioactives delivery. However, their full potential is underexplored. Future applications should study the encapsulation potential of new natural bioactives and show more specialized solutions that address specific requirements; an improved product performance and a pleasant sensory profile could lead to increased customer compliance with the product use.

Epigallocatechin-3-gallate Synergistically Inhibits the Proliferation of Lung Cancer Cells with Gemcitabine by Induction of Apoptosis Mediated by ROS Generation.

The present study focused on the formulation, characterization, and evaluation of solid lipid nanoparticles (SLNs) loaded with gemcitabine (GEM) and epigallocatechin-3-gallate (EGCG) for lung cancer treatment. A 2-level, 3-factor factorial design was used to optimize various process parameters in the preparation of SLNs. The average particle size and polydispersity index (PDI) of GEM-EGCG SLNs were found to be 122.8 ± 8.02 and 0.1738 ± 0.02, respectively. Drug loading and release studies indicated a sustained release behavior for GEM-EGCG SLNs, with release kinetics confirmed by the Higuchi model. Cell viability and anticancer activities were assessed using the MTT assay, which determined an IC50 value of 12.5 μg/mL for GEM-EGCG SLNs against A549 cell lines (lung carcinoma epithelial cells). The SLNs were able to internalize into the nuclei of cells, likely due to their small particle size, and were effective in killing cancer cells. Additionally, a study of ROS production-mediated apoptosis of A549 cells was performed through FACS. GEM-EGCG SLNs were found to be stable for 3 months. In vivo studies revealed better drug distribution in the lungs and improved pharmacokinetic profile compared with pure drugs. Overall, the results suggest that combining GEM and EGCG in biocompatible SLNs has resulted in synergistic antitumor potential and improved bioavailability for both drugs, making it a promising anticancer therapeutic regimen against lung cancer.

Clinical and Market Analysis of NanoBEO: A Public-Worth, Innovative Therapy for Behavioral and Psychological Symptoms of Dementia (BPSD)-Emerging Evidence and Its Implications for a Health Technology Assessment (HTA) and Decision-Making in National Health Systems.

According to scientific literature, some 99% of patients affected by Alzheimer's disease (AD) suffer from behavioral and psychological symptoms of dementia (BPSD), also known as neuropsychiatric symptoms (NPSs). In particular, agitation is one of the most difficult disorders to treat. States of agitation represent a very serious problem as they make these subjects dangerous for themselves and others and worsen as the disease advances. To date, there are no specific solutions for treating agitation. The only authorized drug is risperidone (as well as brexpiprazole, approved by the FDA on 11 May 2023), which can be used for no longer than 6-12 weeks because it increases the risk of death-owing to cardiocerebrovascular accidents-by 1.6-1.7 times. In order to address the latter noteworthy unmet medical need, NanoBEO was produced. The aim of the present work is to generate the health technology assessment (HTA) of this nanotechnological device. The latter consists of a controlled release system, based on solid lipid nanoparticles loaded with bergamot essential oil (BEO). The results of the present research assessed the current evidence in the field of non-pharmacological treatments for this condition, including relevant primary preclinical and clinical data studies supporting the use of this device and the production of the operative plan for its launch on the market. The findings offer recommendations for decision-making on its implementation in dementia. NanoBEO represents a public-worth innovation in this neglected area, marking a significant advancement in the history of dementia, moving from academic research to product development.