Telmisartan loaded lipid nanocarrier as a potential repurposing approach to treat glioma: characterization, apoptosis evaluation in U87MG cells, pharmacokinetic and molecular simulation study.

The study explores anticancer potential of telmisartan (TS) loaded lipid nanocarriers (TLNs) in glioma cells as a potential repurposing nanomodality along with estimation of drug availability at rat brain. Experimental TLNs were produced by previously reported method and characterized.In vitroanticancer efficacy of experimental TLNs was estimated by MTT, confocal microscopy, and FACs analysis in glioma cells. Plasma and brain pharmacokinetic (PK) parameters were also analysed by LCMS/MS. Spherical, nanosized, homogenous, unilamellar, TLNs were reported having desirable drug loading (9.5% ± 0.6%), negative zeta potential and sustained TS release tendency. FITC-TLNs were sufficiently internalized into U87MG cells line within 0.5 h incubation period. IC50for TLNs was considerably higher than free TS in the tested glioma cell lines. Further, TLNs induced superior apoptotic effect in U87MG cells than TS. PK (plasma/brain) data depicted higher AUC,Vss, MRT with lower Cltfor TLNs suggesting improved bioavailability,in vivoresidence and sustained drug availability than free TS administration. Docking studies rationalizedin vitro/in vivoresults as preferably higher binding affinity (docking score:12.4) was detected for TS with glioma proteins. Further,in vivostudies in glioma bearing xenograft model is underway for futuristic clinical validation of TLNs.

Ultrasonic synthesis of green lipid nanocarriers loaded with Scutellaria barbata extract: a sustainable approach for enhanced anticancer and antibacterial therapy.

Ultrasonic manufacturing has emerged as a promising eco-friendly approach to synthesize lipid-based nanocarriers for targeted drug delivery. This study presents the novel ultrasonic preparation of lipid nanocarriers loaded with Scutellaria barbata extract, repurposed for anticancer and antibacterial use. High-frequency ultrasonic waves enabled the precise self-assembly of DSPE-PEG, Span 40, and cholesterol to form nanocarriers encapsulating the therapeutic extract without the use of toxic solvents, exemplifying green nanotechnology. Leveraging the inherent anticancer and antibacterial properties of Scutellaria barbata, the study demonstrates that lipid encapsulation enhances the bioavailability and controlled release of the extract, which is vital for its therapeutic efficacy. Dynamic light scattering and transmission electron microscopy analyses confirmed the increase in size and successful encapsulation post-loading, along with an augmented negative zeta potential indicating enhanced stability. A high encapsulation efficiency of 91.93% was achieved, and in vitro assays revealed the loaded nanocarriers' optimized release kinetics and improved antimicrobial potency against Pseudomonas aeruginosa, compared to the free extract. The combination of ultrasonic synthesis and Scutellaria barbata in an eco-friendly manufacturing process not only advances green nanotechnology but also contributes to sustainable practices in pharmaceutical manufacturing. The data suggest that this innovative nanocarrier system could provide a robust platform for the development of nanotechnology-based therapeutics, enhancing drug delivery efficacy while aligning with environmental sustainability.

Lipid-, Inorganic-, Polymer-, and DNA-Based Nanocarriers for Delivery of the CRISPR/Cas9 system.

The clustered regularly interspaced short palindromic repeat (CRISPR)/associated protein 9 (CRISPR/Cas9) system has been widely explored for the precise manipulation of target DNA and has enabled efficient genomic editing in cells. Recently, CRISPR/Cas9 has shown promising potential in biomedical applications, including disease treatment, transcriptional regulation and genome-wide screening. Despite these exciting achievements, efficient and controlled delivery of the CRISPR/Cas9 system has remained a critical obstacle to its further application. Herein, we elaborate on the three delivery forms of the CRISPR/Cas9 system, and discuss the composition, advantages and limitations of these forms. Then we provide a comprehensive overview of the carriers of the system, and focus on the nonviral nanocarriers in chemical methods that facilitate efficient and controlled delivery of the CRISPR/Cas9 system. Finally, we discuss the challenges and prospects of the delivery methods of the CRISPR/Cas9 system in depth, and propose strategies to address the intracellular and extracellular barriers to delivery in clinical applications.

Lipid-Based Nanocarriers in the Treatment of Glioblastoma Multiforme (GBM): Challenges and Opportunities.

Glioblastoma multiforme (also known as glioblastoma; GBM) is one of the most malignant types of brain tumors that occurs in the CNS. Treatment strategies for glioblastoma are majorly comprised of surgical resection, radiotherapy, and chemotherapy along with combination therapy. Treatment of GBM is itself a tedious task but the involved barriers in GBM are one of the main impediments to move one step closer to the treatment of GBM. Basically, two of the barriers are of utmost importance in this regard, namely blood brain barrier (BBB) and blood brain tumor barrier (BBTB). This review will address different challenges and barriers in the treatment of GBM along with their etiology. The role and recent progress of lipid-based nanocarriers like liposomes, solid lipid nanocarriers (SLNs), nanostructured lipid carriers (NLCs), lipoplexes, and lipid hybrid carriers in the effective management of GBM will be discussed in detail.

Lipid-Based Nanocarriers via Nose-to-Brain Pathway for Central Nervous System Disorders.

Neurodegenerative disorders are distinguished by the gradual deterioration of the nervous system's structure and function due to oxidative stress, mitochondrial dysfunction, protein misfolding, excitotoxicity, and neuroinflammation. Among these NDs, Alzheimer's disease, Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis characterized an increasing dysfunction and loss of neuronal structure leading to neuronal cell death. Although there is currently no drug to totally reverse the effects of NDs, such novel formulations and administration routes are developed for better management and nose-to-brain delivery is one of delivery for treating NDs. This review aimed to highlight advances in research on various lipid based nanocarriers such as liposomes, solid lipid nanoparticles, nanostructured lipid carriers, microemulsion, nanoemulsion, and cubosomes which are reported to treat and alleviate the symptoms of NDs via nose-to-brain route. The challenges during clinical translation of lipid nanocarriers from bench to bed side is also discussed.

Exploration of Lipid-Based Nanocarriers as Drug Delivery Systems in Diabetic Foot Ulcer.

Diabetes mellitus is a chronic manifestation characterized by high levels of glucose in the blood resulting in several complications including diabetic wounds and ulcers, which predominantly require a longer duration of treatment and adversely affect the quality of life of the patients. Nanotechnology-based therapeutics (both intrinsic and extrinsic types) have emerged as a promising treatment in diabetic foot ulcer/chronic wounds owing to their unique characteristics and specific functional properties. In this review, we have focused on the significance of the use of lipids in the healing of diabetic ulcers, their interaction with the injured skin, and recent trends in lipid-based nanocarriers for the healing of diabetic wounds. Lipid nanocarriers are also being investigated for gene therapy in diabetic wound healing to encapsulate nucleic acids such as siRNA and miRNA, which could silence the expression of inflammatory cytokines overexpressed in chronic wounds. Additionally, these are also being explored for encapsulating proteins, peptides, growth factors, and other biological genetic material as therapeutic agents. Lipid-based nanocarriers encompassing a wide variety of carriers such as liposomes, niosomes, ethosomes, solid lipid nanoparticles, and lipidoid nanoparticles that are explored for the treatment of foot ulcers supplemented with relevant research studies have been discussed in the present review. Lipid-based nanodrug delivery systems have demonstrated promising wound healing potential, particularly in diabetic conditions due to the enhanced efficacy of the entrapped active molecules.

Acylglycerols of Myristic Acid as New Candidates for Effective Stigmasterol Delivery-Design, Synthesis, and the Influence on Physicochemical Properties of Liposomes.

New carriers of phytosterols; acylglycerols containing natural myristic acid at sn-1 and sn-3 positions and stigmasterol residue linked to sn-2 position by carbonate and succinate linker have been designed and synthesized in three-step synthesis from dihydroxyacetone (DHA). The synthetic pathway involved Steglich esterification of DHA with myristic acid; reduction of carbonyl group of 1,3-dimyristoylpropanone and esterification of 1,3-dimyristoylglicerol with stigmasterol chloroformate or stigmasterol hemisuccinate. The structure of the obtained hybrids was established by the spectroscopic methods (NMR; IR; HRMS). Obtained hybrid molecules were used to form new liposomes in the mixture with model phospholipid and their effect on their physicochemical properties was determined, including the polarity, fluidity, and main phase transition of liposomes using differential scanning calorimetry and fluorimetric methods. The results confirm the significant effect of both stigmasterol-containing acylglycerols on the hydrophilic and hydrophobic region of liposome membranes. They significantly increase the order in the polar heads of the lipid bilayer and increase the rigidity in the hydrophobic region. Moreover, the presence of both acylglycerols in the membranes shifts the temperature of the main phase transition towards higher temperatures. Our results indicate stabilization of the bilayer over a wide temperature range (above and below the phase transition temperature), which in addition to the beneficial effects of phytosterols on human health makes them more attractive components of novel lipid nanocarriers compared to cholesterol.

Impact of highly phospholipid-containing lipid nanocarriers on oral bioavailability and pharmacodynamics performance of genistein.

Oxidative stress is a leading cause of different diseases. Genistein is a valuable bioflavonoid possessing antioxidant and anti-inflammatory activity but unfortunately, it suffers from low aqueous solubility, extremely poor bioavailability and first pass effect when used in its pure state. The aim of this work was to formulate and characterize genistein-loaded highly phospholipid-containing lipid nanocarriers to improve oral bioavailability and pharmacodynamic performance. Lipid nanocarriers were prepared by the emulsification/sonication technique. The influence of phospholipid percentage (1%-10%) on physicochemical properties, drug release and stability was investigated. The particle size, zeta potential and EE% were in ranges from 211.9 ± 21.6 to 342.3 ± 7.9 nm, -11.6 ± 1.7 to -19.4 ± 3.1 mV and 78.5 ± 4.7% to 92.2 ± 1.9%, respectively. Drug release was less predominant in the case of SLN formulations when compared to corresponding NLC formulations. High phospholipid percentage produced less stable formulations in terms of particle size growth, gelation and heterogeneous particle distributions. DSC, FT-IR and XRD tools revealed that genistein has existed in an amorphous form in NLC4. The bioavailability of NLC4 was approximately 2.6-fold greater than that of conventional suspension. Additionally, lipid peroxidation in liver homogenate and histopathological alterations in liver and kidney sections were particularly improved, providing a promising strategy for oral administration of genistein.

Improved biopharmaceutical performance of antipsychotic drug using lipid nanoparticles via intraperitoneal route.

This study aims to develop, characterize, and examine olanzapine-loaded solid lipid nanocarriers (OLAN-SLNs) for effective brain delivery. OLAN has poor water solubility and low penetration through blood-brain barrier (BBB). Herein, OLAN-SLNs were fabricated using high-pressure homogenization (HPH) method followed by their investigation for particle properties. Moreover, in vitro release and in vivo pharmacokinetics profiles of OLAN-SLNs were compared with pure drug. Anti-psychotic activity was performed in LPS-induced psychosis mice model. Furthermore, expressions of the COX-2 and NF-κB were measured trailed by histopathological examination. The optimized formulation demonstrated nanoparticle size (149.1 nm) with rounded morphology, negative zeta potential (-28.9 mV), lower PDI (0.334), and excellent entrapment efficiency (95%). OLAN-SLNs significantly retarded the drug release and showed sustained release pattern as compared to OLAN suspension. Significantly enhanced bioavailability (ninefold) was demonstrated in OLAN-SLNs when compared with OLAN suspension. Behavioral tests showed significantly less immobility and more struggling time in OLAN-SLNs treated mice group. Additionally, reduced expression of COX-2 and -NF κB in brain was found. Altogether, it can be concluded that SLNs have the potential to deliver active pharmaceutical ingredients to brain, most importantly to enhance their bioavailability and antipsychotic effect, as indicated for OLAN in this study.

In vivo toxicity evaluation of nanoemulsions for drug delivery.

Lipid nanocarriers (LNs), for example nanoemulsions (NE), are an emerging tool for drug delivery due to their ability to incorporate drugs, protect the drug from degradation, improve bioavailability, and control release. Although LNs are widely studied and applied, especially in the pharmaceutical field, knowledge about their toxicity is scarce. Moreover, the majority of studies focus on their efficiency rather than safety. Thus, the aim of this study was to evaluate the possible toxic effects of NE in vivo. Male Wistar rats (2 months old, 250 g) were treated once daily for 21 days with NE via oral or intraperitoneal delivery at 200, 400 or 800 mg lipid/kg body weight. At the end of the experiment, biochemical, hematological, oxidative stress, and genotoxicity parameters were analyzed. Our results showed that treatment with NE did not modify organ weight or biochemical parameters when compared to controls. The highest NE dose (800 mg/kg) via intraperitoneal injection caused changes in hematological parameters, namely increased plasma proteins, platelets, total leukocytes, and neutrophils, findings that suggest an inflammatory reaction. Further, the same dose evoked lipid peroxidation in the liver. Taken together, the results from this study suggest that NEs can be considered safe for oral administration, but high doses via the parenteral route can cause toxic effects. This study contributes to knowledge about NE toxicity and provides important data about their safe use in the pharmaceutical field.

Formulative Study and Intracellular Fate Evaluation of Ethosomes and Transethosomes for Vitamin D3 Delivery.

In this pilot study, ethosomes and transethosomes were investigated as potential delivery systems for cholecalciferol (vitamin D3), whose deficiency has been correlated to many disorders such as dermatological diseases, systemic infections, cancer and sarcopenia. A formulative study on the influence of pharmaceutically acceptable ionic and non-ionic surfactants allowed the preparation of different transethosomes. In vitro cytotoxicity was evaluated in different cell types representative of epithelial, connective and muscle tissue. Then, the selected nanocarriers were further investigated at light and transmission electron microscopy to evaluate their uptake and intracellular fate. Both ethosomes and transethosomes proven to have physicochemical properties optimal for transdermal penetration and efficient vitamin D3 loading; moreover, nanocarriers were easily internalized by all cell types, although they followed distinct intracellular fates: ethosomes persisted for long times inside the cytoplasm, without inducing subcellular alteration, while transethosomes underwent rapid degradation giving rise to an intracellular accumulation of lipids. These basic results provide a solid scientific background to in vivo investigations aimed at exploring the efficacy of vitamin D3 transdermal administration in different experimental and pathological conditions.

Nanotechnologies for intranasal drug delivery: an update of literature.

Scientific research has focused its attention on finding an alternative route to systemic oral and parenteral administration, to overcome their usual drawbacks, such as hepatic first-pass which decreases drug bioavailability after oral administration, off-target effects, low patient compliance and low speed of onset of the pharmacological action in first-aid cases. Innovative drug delivery systems (DDS), mainly based on polymer and lipid biocompatible materials, have given a great prompt in this direction in the last years. The intranasal (IN) route of administration is a valid non-invasive alternative. It is highly suitable for self-administration, the drug quickly reaches the bloodstream, largely avoiding the first pass effect, and can also reach directly the brain bypassing BBB. Association of IN route with DDS can thus become a winning strategy for the controlled delivery of drugs, especially when a very quick effect is desired or needed. This review aims at analyzing the scientific literature regarding IN-DDS and their different ways of administration (systemic, topical, pulmonary, nose-to-brain). In particular, attention was devoted to polymer- and lipid-based micro- and nanocarriers, being the topic of most published articles in the last decade, but the whole plethora of colloidal DDS investigated in recent years for IN administration was presented.

Formulation and Evaluation of Topical Biodegradable Films Loaded with Levofloxacin Lipid Nanocarriers.

Skin ulcers have increased sharply due to rise in the incidence of obesity and diabetes. This study investigated lipid nanocarriers as a strategy to improve the efficacy of levofloxacin (LV) in penetrating skin. Two surfactant types and different lipid mixtures were used in preparation of lipid nanocarriers. Mean particle size, percentage entrapment efficiency (%EE), in vitro release, and antimicrobial activity were examined. The selected formula was incorporated into a chitosan (CS) film that was subjected to physic-chemical characterization and ex vivo permeation study. The selected formula showed particle size, PDI, and ZP: 80.3 nm, -0.21, and -26 mV, respectively, synchronized with 82.12 %EE. In vitro release study showed slow biphasic release of LV from lipid nanocarriers. The antimicrobial effect illustrated statistically significant effect of lipid nanocarriers on decreasing the minimum effective concentration (MIC) of LV, particularly against E. coli. The optimized nanocarriers' formula loaded into CS film was clear, colorless, translucent, and smooth in texture. Based on the release profiles, it could be speculated that the CS film loaded with LV nanocarriers can maintain the antibacterial activity for 4 consecutive days. Thus, the local delivery of the drug in a sustained release manner could be predicted to enhance the therapeutic effect. Further clinical studies are strongly recommended. Graphical Abstract.

Recent Advancement in Topical Nanocarriers for the Treatment of Psoriasis.

Psoriasis is a life-threatening autoimmune inflammatory skin disease, triggered by T lymphocyte. Recently, the drugs most commonly used for the treatment of psoriasis include methotrexate (MTX), cyclosporine (CsA), acitretin, dexamethasone, and salicylic acid. However, conventional formulations due to poor absorptive capacity, inconsistent drug release characteristics, poor capability of selective targeting, poor retention of drug molecules in target tissue, and unintended skin reactions restrict the clinical efficacy of drugs. Advances in topical nanocarriers allow the development of prominent drug delivery platforms can be employed to address the critical issues associated with conventional formulations. Advances in nanocarriers design, nano-dimensional configuration, and surface functionalization allow formulation scientists to develop formulations for a more effective treatment of psoriasis. Moreover, interventions in the size distribution, shape, agglomeration/aggregation potential, and surface chemistry are the significant aspects need to be critically evaluated for better therapeutic results. This review attempted to explore the opportunities and challenges of current revelations in the nano carrier-based topical drug delivery approach used for the treatment of psoriasis.

Nanostructured lipid carriers (NLCs) as drug delivery platform: Advances in formulation and delivery strategies.

NLCs have provoked the incessant impulsion for the development of safe and valuable drug delivery systems owing to their exceptional physicochemical and then biocompatible characteristics. Throughout the earlier period, a lot of studies recounting NLCs based formulations have been noticeably increased. They are binary system which contains both solid and liquid lipids aiming to produce less ordered lipidic core. Their constituents particularly influence the physicochemical properties and effectiveness of the final product. NLCs can be fabricated by different techniques which are classified according to consumed energy. More utilization NLCs is essential due to overcome barriers surrounded by the technological procedure of lipid-based nanocarriers' formulation and increased information of the core mechanisms of their transport via various routes of administration. They can be used in different applications and by different routes such as oral, cutaneous, ocular and pulmonary. This review article seeks to present an overview on the existing situation of the art of NLCs for future clinics through exposition of their applications which shall foster their lucid use. The reported records evidently demonstrate the promise of NLCs for innovate therapeutic applications in the future.

Emerging Trends in Topical Delivery of Curcumin Through Lipid Nanocarriers: Effectiveness in Skin Disorders.

Curcumin is a unique molecule naturally obtained from rhizomes of Curcuma longa. Curcumin has been reported to act on diverse molecular targets like receptors, enzymes, and co-factors; regulate different cellular signaling pathways; and modulate gene expression. It suppresses expression of main inflammatory mediators like interleukins, tumor necrosis factor, and nuclear factor κB which are involved in the regulation of genes causing inflammation in most skin disorders. The topical delivery of curcumin seems to be more advantageous in providing a localized effect in skin diseases. However, its low aqueous solubility, poor skin permeation, and degradation hinder its application for commercial use despite its enormous potential. Lipid-based nanocarrier systems including liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, lyotropic liquid crystal nanoparticles, lipospheres, and lipid nanocapsules have found potential as carriers to overcome the issues associated with conventional topical dosage forms. Nano-size, lipophilic nature, viscoelastic properties, and occlusive effect of lipid nanocarriers provide high drug loading, hydration of skin, stability, enhanced permeation through the stratum corneum, and slow release of curcumin in the targeted skin layers. This review particularly focuses on the application of lipid nanocarriers for the topical delivery of curcumin in the treatment of various skin diseases. Furthermore, preclinical studies and patents have also indicated the emerging commercialization potential of curcumin-loaded lipid nanocarriers for effective drug delivery in skin disorders. Graphical Abstract.

Formulation-optimization of solid lipid nanocarrier system of STAT3 inhibitor to improve its activity in triple negative breast cancer cells.

In the present study, solid lipid nanoparticles (SLNs) have been formulated as a carrier system for effective intracellular delivery of STAT3 inhibitor, niclosamide (Niclo) to triple negative breast cancer (TNBC) cells. Emulsification-solvent evaporation method was employed in formulation of Niclo-loaded SLNs (Niclo-SLNs). The formula of Niclo-SLN was optimized by Box-Behnken design and characterized for their shape, size, and surface charge. The in vitro anti-cancer efficacy of Niclo-SLNs was studied in TNBC cells. The prepared Niclo-SLNs were found to be spherical with the particle size of 112.18 ± 1.73 nm and zetapotential of 23.8 ± 2.7 mV. In the in vitro anticancer study the Niclo SLNs show a better cytotoxicity than the naïve Niclo, which is attributed to improved cell uptake of SLN formulation. In conclusion, the results of the present study demonstrate that the formulation of Niclo as SLNs will improve the anticancer efficacy against TNBC.

Development, Optimization, and In Vitro/In Vivo Characterization of Enhanced Lipid Nanoparticles for Ocular Delivery of Ofloxacin: the Influence of Pegylation and Chitosan Coating.

This study aims to investigate whether modification of solid lipid nanoparticles (SLNs) with chitosan (CTS) and polyethylene glycol (PEG) coatings enhances corneal retention time and transcorneal bioavailability. Ofloxacin (OFLOX) was selected as the model drug because of its potential benefits for the treatment of local eye infections. The OFLOX-CTS-PEG-SLN was prepared by a modified emulsion/solvent evaporation technique. A central composite design was implemented to investigate the influence of total lipid/drug ratio, surfactant concentration, PEG stearate concentration in the lipid mixture, and CTS concentration on size, entrapment, transcorneal permeation, and adhesion to the corneal mucosal membrane. The optimized OFLOX-CTS-PEG-SLN was characterized for OFLOX cumulative percentage released in simulated tear fluid and permeated across the excised bovine corneal membrane. Moreover, nanoparticle morphology, eye irritation via histopathological analysis, and OFLOX concentration in the ocular fluids and tissues were determined. A total lipid/drug ratio of 19:1, Tween 80 of 2%, PEG stearate concentration in the lipid mixture (% w/w) of 2.6%, and CTS concentration (% w/v) of 0.23% produced 132.9 nm particles entrapping 74.8% of the total drug added. The particles detached from the corneal membrane at a force of 3700 dyne/cm2. The %OFLOX released from the optimized nanoparticles was 63.3, and 66% of the drug permeated after 24 h. Compared to Oflox® drops, the optimized OFLOX-CTS-PEG-SLN exhibited similar tolerability but two- to threefold higher concentrations in the eyes of rabbits. Coating of SLN with chitosan and PEG augments the ocular bioavailability of OFLOX by increasing transcorneal permeation and enhancing mucoadhesion strength.

Preclinical Explorative Assessment of Celecoxib-Based Biocompatible Lipidic Nanocarriers for the Management of CFA-Induced Rheumatoid Arthritis in Wistar Rats.

Celecoxib (CXB), a COX-2 inhibitor, is primarily indicated for long-term treatment of rheumatoid arthritis (RA). The effective therapeutic efficacy of CXB on RA via oral administration shows adverse systemic complications, and therefore, local application of CXB has been recommended. The aim of the present study was to develop and characterize solid lipid nanoparticles (SLNs) with enhanced skin permeation potential of CXB. The particle size, polydispersity index (PDI), and percentage drug entrapment (PDE) of the developed SLNs (CXB-SLNs) were found to be 240 nm, < 0.3, and ~ 86% respectively. The developed SLNs exhibited sustained release up to 70% at the end of 48 h. Drug permeation was found to be 45% for SLN gel and 31% for conventional gel. The dermatokinetic studies also confirmed enhanced permeation of CXB in the epidermis and dermis and revealed superiority of the developed SLN gel vis-à-vis the conventional gel. Further, in the CFA-induced arthritis rat model, % arthritis index (AI) of the CXB-SLN gel formulation was found to be very less (18.54%) as compared to untreated (187.34%) and conventional gel-treated (91.61%) animals. In conclusion, the current study can provide a suitable alternative for the development of an effective topical formulation of CXB in lipid nanocarriers.

How can lipid nanocarriers improve transdermal delivery of olanzapine?

The development of a transdermal nanocarrier drug delivery system with potential for the treatment of psychiatric disorders, such as schizophrenia and bipolar disorder, is described. Lipid nanocarriers (LN), encompassing various solid:liquid lipid compositions were formulated and assessed as potential nanosystems for transdermal delivery of olanzapine. A previously optimized method of hot high pressure homogenization (HPH) was adopted for the production of the LN, which comprised solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsions (NE). Precirol ® was selected as the solid lipid for progression of studies. SLN exhibited the best performance for transdermal delivery of olanzapine, based on in vitro release and permeation studies, coupled with results from physicochemical characterization of several solid:liquid lipid formulations. Stability tests, performed to give an indication of long-term storage behavior of the formulations, were in good agreement with previous studies for the best choice of solid:liquid lipid ratio. Overall, these findings highlight the SLN-based formulation as promising for the further inclusion in and production of transdermal patches, representing an innovative therapeutic approach.