Mucoadhesive Chitosan Composite Sponge as a Carrier for ß-Sitosterol Cubosomes for Thermal Burn Treatment.

Our study aimed to explore the potential of using nanostructured lipid carriers (NLCs) to enhance the topical administration of ß-sitosterol, a bioactive that is poorly soluble in water. Here, we have taken advantage of the unique characteristics that cubosomes have to provide as a drug delivery system. These characteristics include a large surface area, thermal stability, and the capacity to encapsulate molecules that are hydrophobic, amphiphilic, and hydrophilic. The cubosomal formulation was optimized by building a central composite design. The optimum dispersion exhibited a particle size of 88.3 nm, a zeta potential of -43, a polydispersity index of 0.358, and drug entrapment of 95.6%. It was composed of 15% w/w oleic acid and 5% w/w pluronic F127. The optimized cubosome dispersion was incorporated into a sponge formulation. The optimized cubosome sponge achieved a higher drug release compared with the cubosome dispersion. The SEM micrograph of the selected sponge showed that it has an interwoven irregular fibrous lamellar structure with low density and high porosity. The in-vivo data revealed that topical application of the ß-sitosterol cubosomal sponge showed significant higher wound closure percentage relative to the ß-sitosterol product (Mebo)®.

The gastroprotective effect of Yucca filamentosa standardized crude leaves extract versus its nano-cubosomal formulation in ethanol-induced gastric injury.

Yucca filamentosa (YF) is widely used in folk medicine for its anti-inflammatory effects. Our study aimed to evaluate the chemical profile of YF extracts. Additionally, the gastroprotective efficacy of its crude leaf extract and nano-cubosomal formulation was assessed in a rat model of ethanol-induced gastric injury by altering the HMGB-1/RAGE/TLR4/NF-κB pathway. The phytochemical composition of YF was investigated using FTIR spectroscopy and LC-MS/MS techniques. Standardization was further accomplished using HPLC. Rats were treated orally with yucca crude extract or its nano-cubosomal formulation at doses of 25, 50, and 100 mg/kg. Famotidine (50 mg/kg, IP) was used as a reference drug. After 1 h, rats were administered ethanol (1 ml, 95 %, orally). One hour later, the rats were sacrificed, and the serum was separated to determine TNF-α and IL-6 levels. Stomachs were excised for the calculation of the ulcer index and histopathological examinations. Stomach tissue homogenate was used to determine MDA and catalase levels. Additionally, the expression levels of HMGB-1/RAGE/TLR4/NF-κB were assessed. Phytochemical analysis confirmed the predominance of steroidal saponins, sucrose, organic and phenolic acids, and kaempferol. The nano-cubosomal formulation demonstrated enhanced gastroprotective, anti-oxidant, and anti-inflammatory efficacy compared to the crude extract at all tested doses. The most prominent effect was observed in rats pretreated with the YF nano-cubosomal formulation at a dose of 100 mg/kg, which was similar to normal control and famotidine-treated rats. Our results highlighted the enhanced gastroprotective impact of the yucca nano-cubosomal formulation in a dose-dependent manner. This suggests its potential use in preventing peptic ulcer recurrence.

Cubosomes functionalized with antibodies as a potential strategy for the treatment of HER2-positive breast cancer.

Breast cancers that overexpress human epidermal growth factor receptor 2 (HER2) have poor prognosis. Moreover, available chemotherapies cause numerous side effects due to poor selectivity. To advance more effective and safer therapies for HER2-positive breast cancer, we explored the fusion of drug delivery technology and immunotherapy. Our research led to the design of immunocubosomes loaded with panobinostat and functionalized with trastuzumab antibodies, enabling precise targeting of breast cancer cells that overexpress HER2. We characterised the nanostructure of cubosomes using small-angle X-ray scattering (SAXS), cryo-transmission electron microscopy (cryo-TEM), and dynamic light scattering (DLS). Moreover, we confirmed the integrity of the trastuzumab antibodies on the immunocubosomes by Fourier-transform infrared spectroscopy (FTIR) and sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Additionally, we found that panobinostat-loaded immunocubosomes were more cytotoxic, and in an uptake-dependant manner, towards a HER2-positive breast cancer cell line (SKBR3) compared to a cell line representing healthy cells (L929). These results support that the functionalization of cubosomes with antibodies enhances both the effectiveness of the loaded drug and its selectivity for targeting HER2-positive breast cancer cells.

Verapamil-Loaded Cubosomes for Enhancing Intranasal Drug Delivery: Development, Characterization, Ex Vivo Permeation, and Brain Biodistribution Studies.

Verapamil hydrochloride (VRP), an antihypertensive calcium channel blocker drug has limited bioavailability and short half-life when taken orally. The present study was aimed at developing cubosomes containing VRP for enhancing its bioavailability and targeting to brain for cluster headache (CH) treatment as an off-label use. Factorial design was conducted to analyze the impact of different components on entrapment efficiency (EE%), particle size (PS), zeta potential (ZP), and percent drug release. Various in-vitro characterizations were performed followed by pharmacokinetic and brain targeting studies. The results revealed the significant impact of glyceryl monooleate (GMO) on increasing EE%, PS, and ZP of cubosomes with a negative influence on VRP release. The remarkable effect of Poloxamer 407 (P407) on decreasing EE%, PS, and ZP of cubosomes was observed besides its influence on accelerating VRP release%. The DSC thermograms indicated the successful entrapment of the amorphous state of VRP inside the cubosomes. The design suggested an optimized formulation containing GMO (50% w/w) and P407 (5.5% w/w). Such formulation showed a significant increase in drug permeation through nasal mucosa with high Er value (2.26) when compared to VRP solution. Also, the histopathological study revealed the safety of the utilized components used in the cubosomes preparation. There was a significant enhancement in the VRP bioavailability when loaded in cubosomes owing to its sustained release favored by its direct transport to brain. The I.N optimized formulation had greater BTE% and DTP% at 183.53% and 90.19%, respectively in comparison of 41.80% and 59% for the I.N VRP solution.

Small-angle X-ray and neutron scattering applied to lipid-based nanoparticles: Recent advancements across different length scales.

Lipid-based nanoparticles (LNPs), ranging from nanovesicles to non-lamellar assemblies, have gained significant attention in recent years, as versatile carriers for delivering drugs, vaccines, and nutrients. Small-angle scattering methods, employing X-rays (SAXS) or neutrons (SANS), represent unique tools to unveil structure, dynamics, and interactions of such particles on different length scales, spanning from the nano to the molecular scale. This review explores the state-of-the-art on scattering methods applied to unveil the structure of lipid-based nanoparticles and their interactions with drugs and bioactive molecules, to inform their rational design and formulation for medical applications. We will focus on complementary information accessible with X-rays or neutrons, ranging from insights on the structure and colloidal processes at a nanoscale level (SAXS) to details on the lipid organization and molecular interactions of LNPs (SANS). In addition, we will review new opportunities offered by Time-resolved (TR)-SAXS and -SANS for the investigation of dynamic processes involving LNPs. These span from real-time monitoring of LNPs structural evolution in response to endogenous or external stimuli (TR-SANS), to the investigation of the kinetics of lipid diffusion and exchange upon interaction with biomolecules (TR-SANS). Finally, we will spotlight novel combinations of SAXS and SANS with complementary on-line techniques, recently enabled at Large Scale Facilities for X-rays and neutrons. This emerging technology enables synchronized multi-method investigation, offering exciting opportunities for the simultaneous characterization of the structure and chemical or mechanical properties of LNPs.

A Versatile Synthesis Platform Based on Polymer Cubosomes for a Library of Highly Ordered Nanoporous Metal Oxides Particles.

Polymer cubosomes (PCs) have well-defined inverse bicontinuous cubic mesophases formed by amphiphilic block copolymer bilayers. The open hydrophilic channels, large periods, and robust physical properties of PCs are advantageous to many host-guest interactions and yet not fully exploited, especially in the fields of functional nanomaterials. Here, the self-assembly of poly(ethylene oxide)-block-polystyrene block copolymers is systematically investigated and a series of robust PCs is developed via a cosolvent method. Ordered nanoporous metal oxide particles are obtained by selectively filling the hydrophilic channels of PCs via an impregnation strategy, followed by a two-step thermal treatment. Based on this versatile PC platform, the general synthesis of a library of ordered porous particles with different pore structures 3 ¯ $\bar{3}$ 3 ¯ $\bar{3}$ , tunable large pore size (18-78 nm), high specific surface areas (up to 123.3 m2 g-1 for WO3) and diverse framework compositions, such as transition and non-transition metal oxides, rare earth chloride oxides, perovskite, pyrochlore, and high-entropy metal oxides is demonstrated. As typical materials obtained via this method, ordered porous WO3 particles have the advantages of open continuous structure and semiconducting properties, thus showing superior gas sensing performances toward hydrogen sulfide.

Liposomes to Cubosomes: The Evolution of Lipidic Nanocarriers and Their Cutting-Edge Biomedical Applications.

Lipidic nanoparticles have undergone extensive research toward the exploration of their diverse therapeutic applications. Although several liposomal formulations are in the clinic (e.g., DOXIL) for cancer therapy, there are many challenges associated with traditional liposomes. To address these issues, modifications in liposomal structure and further functionalization are desirable, leading to the emergence of solid lipid nanoparticles and the more recent liquid lipid nanoparticles. In this context, "cubosomes", third-generation lipidic nanocarriers, have attracted significant attention due to their numerous advantages, including their porous structure, structural adaptability, high encapsulation efficiency resulting from their extensive internal surface area, enhanced stability, and biocompatibility. Cubosomes offer the potential for both enhanced cellular uptake and controlled release of encapsulated payloads. Beyond cancer therapy, cubosomes have demonstrated effectiveness in wound healing, antibacterial treatments, and various dermatological applications. In this review, the authors provide an overview of the evolution of lipidic nanocarriers, spanning from conventional liposomes to solid lipid nanoparticles, with a special emphasis on the development and application of cubosomes. Additionally, it delves into recent applications and preclinical trials associated with cubosome formulations, which could be of significant interest to readers from backgrounds in nanomedicine and clinicians.

A nanocomposite competent to overcome solubility and permeation issues of capsaicin and thiocolchicoside simultaneously in gout management: Fabrication of nanocubosomes.

This study aimed to formulate nano-cubosomes (NCs) co-loaded with capsaicin (CAP) and thiocolchicoside (TCS) to enhance their bioavailability and minimize associated potential side effects through transdermal delivery alongside their synergistic activity. Twenty seven (27) nano-cubosomal dispersions were prepared according to Box-Behnken factorial design and the effect of CAP, TCS, glyceryl mono oleate (GMO) and poloxamer 407 (P407) concentrations on particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency were assessed. The results revealed that the optimized formulation exhibited a mean droplet size of 503 ± 10.3 nm, PDI of 0.405 ± 0.02, zeta potential of -10.0 ± 1.70 mV and entrapment efficiency of 86.9 ± 3.56 %. The in vivo anti-inflammatory effect of optimized formulation was studied in rats by injecting carrageenan to induce edema. The results of in vivo study showed that transdermal application of nano-cubosomes co-loaded with CAP and TCS significantly (p value < 0.05) improved carrageenan induced inflammation compared with standard treatment. The analgesic activity of optimized formulation was evaluated in rats by using Eddy's hot plate method. The findings of analgesic activity illustrated that the analgesic effects exhibited by test formulation may be associated with increased licking period and inhibition of prostaglandins level. In conclusion, the transdermal application of NCs co-loaded with CAP and TCS may be a promising delivery system for enhancing their bioavailability as well as synergistic analgesic and anti-inflammatory activity in gout management.

Development, optimization and characterization of cisplatin loaded cubosomes for human lung carcinoma.

OBJECTIVES: This study aimed to develop, optimize and evaluate glyceryl monooleate (GMO) based cubosomes as a drug delivery system containing cisplatin for treatment of human lung carcinoma. SIGNIFICANCE: The significance of this research was to successfully incorporate slightly water soluble and potent anticancer drug (cisplatin) into cubosomes, which provide slow and sustained release of drug for longer period of time. METHODS: The delivery system was developed through top-down approach by melting GMO and poloxamer 407 (P407) at 70 °C and then drop-wise addition of warm deionized water (70 °C) containing cisplatin. The formulation then exposed to probe sonicator for about 2 min. A randomized regular two level full factorial design with help of Design Expert was used for optimization of blank cubosomal formulations. Cisplatin loaded cubosomes were then subjected to physico-chemical characterization. RESULTS: The characterization of the formulation revealed that it had a sufficient surface charge of -9.56 ± 1.33 mV, 168.25 ± 5.73 nm particle size, and 60.64 ± 0.11% encapsulation efficiency. The in vitro release of cisplatin from the cubosomes at pH 7.4 was observed to be sustained, with 94.5% of the drug being released in 30 h. In contrast, 99% of cisplatin was released from the drug solution in just 1.5 h. In vitro cytotoxicity assay was conducted on the human lung carcinoma NCI-H226 cell line, the cytotoxicity of cisplatin-loaded cubosomes was relative to that of pure cisplatin solution, while blank (without cisplatin) cubosomes were nontoxic. CONCLUSIONS: The obtained results demonstrated the successful development of cubosomes for sustained delivery of cisplatin.

Cubosomes were prepared, optimized, and evaluated for cisplatin delivery.A randomized regular two level full factorial design was constructed to optimize blank cubosomes.Blank cubosomes consisted of GMO as the lipid and P407 as an emulsifying agent.In vitro release studies demonstrated sustained release of cisplatin from cubosomes at pH 7.4.Cytotoxicity assay on human lung carcinoma cell line NCI-H226 showed similar cytotoxicity between cisplatin-loaded cubosomes and pure cisplatin solution while blank cubosomes exhibited no toxicity.

Appraisal of folate functionalized bosutinib cubosomes against hepatic cancer cells: In-vitro, In-silico, and in-vivo pharmacokinetic study.

Targeted therapies enhance the efficacy of tumour screening and management while lowering side effects. Multiple tumours, including liver cancer, exhibit elevated levels of folate receptor expression. This research attempted to develop surface-functionalised bosutinib cubosomes against hepatocellular carcinoma. The novelty of this work is the anti-hepatic action of bosutinib (BST) and folic acid-modified bosutinib cubosomes (BSTMF) established through proto-oncogene tyrosine-protein kinase (SrC)/ focal adhesion kinase(FAK), reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and cell cytotoxicity. Later, the in-vivo pharmacokinetics of BSTMF were determined for the first time. The strong affinity of folic acid (FA) for folate receptors allows BSTMF to enter cells via FA receptor-mediated endocytosis. The particle size of the prepared BSTMF was 188.5 ± 2.25 nm, and its zeta potential was -20.19 ± 2.01 mV, an encapsulation efficiency of 90.31 ± 3.15 %, and a drug release rate of 76.70 ± 2.10 % for 48 h. The surface architecture of BSTMF was identified using transmission electron microscopy (TEM) and Atomic force microscopy (AFM). Cell-line studies demonstrated that BSTMF substantially lowered the viability of Hep G2 cells compared to BST and bosutinib-loaded cubosomes (BSTF). BSTMF demonstrated an elevated BST concentration in tumour tissue than in other organs and also displayed superior pharmacokinetics, implying that they hold potential against hepatic cancers. This is the first study to show that BSTMF may be effective against liver cancer by targeting folate receptors and triggering SrC/FAK-dependent apoptotic pathways. Multiple parameters demonstrated that BSTMF enhanced anticancer targeting, therapeutic efficacy, and safety in NDEA-induced hepatocellular carcinoma.

Investigation of Anticancer Therapy Using pH-Sensitive Carbon Dots-Functionalized Doxorubicin in Cubosomes.

Cancer remains a highly lethal disease due to its elusive early detection, rapid spread, and significant side effects. Nanomedicine has emerged as a promising platform for drug delivery, diagnosis, and treatment monitoring. In particular, carbon dots (CDs), a type of fluorescent nanomaterial, offer excellent fluorescence properties and the ability to carry multiple drugs simultaneously through covalent bonding. In this work, CDs with carbonyl groups on the surface were prepared by aldol condensation and reacted with amine groups in the structure of doxorubicin (DOX) through Schiff base reaction to generate pH-responsive CDs-DOX. On the other hand, cubosomes with three-dimensional lattice structures formed by lipid bilayers have advantageous capabilities of encapsulating various hydrophilic, amphiphilic, and hydrophobic substances. The pH-responsive CDs-DOX are subsequently loaded into cubosomes to form an anticancer therapeutic nanosystem, CDs-DOX@cubosome. Leveraging the unique properties of CDs-DOX and cubosomes, our CDs-DOX@cubosome can enter tumor tissue through the enhanced permeation and retention effect first and conduct membrane fusion with tumor cells to intracellularly release CDs-DOX. Then, the imine bond in CDs-DOX breaks under acidic conditions within human cancer cell lines (HeLa and HepG-2 cells), releasing DOX and achieving enhanced treatment of tumors. Additionally, fluorescent CDs can synchronously achieve real-time in situ diagnosis of tumor tissue. We demonstrate that our CDs-DOX@cubosome works as an excellent drug delivery system with therapeutic efficiency enhancement to the tumor and reduced side effects.

A systematic study of the effect of lipid architecture on cytotoxicity and cellular uptake of cationic cubosomes.

HYPOTHESIS: Lipid nanoparticles containing a cationic lipid are increasingly used in drug and gene delivery as they can display improved cellular uptake, enhanced loading for anionic cargo such as siRNA and mRNA or exhibit additional functionality such as cytotoxicity against cancer cells. This research study tests the hypothesis that the molecular structure of the cationic lipid influences the structure of the lipid nanoparticle, the cellular uptake, and the resultant cytotoxicity. EXPERIMENTS: Three potentially cytotoxic cationic lipids, with systematic variations to the hydrophobic moiety, were designed and synthesised. All the three cationic lipids synthesised contain pharmacophores such as the bicyclic coumarin group (CCA12), the tricyclic etodolac moiety (ETD12), or the large pentacyclic triterpenoid "ursolic" group (U12) conjugated to a quaternary ammonium cationic lipid containing twin C12 chains. The cationic lipids were doped into monoolein cubosomes at a range of concentrations from 0.1 mol% to 5 mol% and the effect of the lipid molecular architecture on the cubosome phase behaviour was assessed using a combination of Small Angle X-Ray Scattering (SAXS), Dynamic Light Scattering (DLS), zeta-potential and cryo-Transmission Electron Microscopy (Cryo-TEM). The resulting cytotoxicity of these particles against a range of cancerous and non-cancerous cell-lines was assessed, along with their cellular uptake. FINDINGS: The molecular architecture of the cationic lipid was linked to the internal nanostructure of the resulting cationic cubosomes with a transition to more curved cubic and hexagonal phases generally observed. Cubosomes formed from the cationic lipid CCA12 were found to have improved cellular uptake and significantly higher cytotoxicity than the cationic lipids ETD12 and U12 against the gastric cancer cell-line (AGS) at lipid concentrations ≥ 75 µg/mL. CCA12 cationic cubosomes also displayed reasonable cytotoxicity against the prostate cancer PC-3 cell-line at lipid concentrations ≥ 100 µg/mL. In contrast, 2.5 mol% ETD12 and 2.5 mol% U12 cubosomes were generally non-toxic against both cancerous and non-cancerous cell lines over the entire concentration range tested. The molecular architecture of the cationic lipid was found to influence the cubosome phase behaviour, the cellular uptake and the toxicity although further studies are necessary to determine the exact relationship between structure and cellular uptake across a range of cell lines.

Angiopep-2-Functionalized Lipid Cubosomes for Blood-Brain Barrier Crossing and Glioblastoma Treatment.

Glioblastoma multiforme (GBM) is an aggressive brain cancer with high malignancy and resistance to conventional treatments, resulting in a bleak prognosis. Nanoparticles offer a way to cross the blood-brain barrier (BBB) and deliver precise therapies to tumor sites with reduced side effects. In this study, we developed angiopep-2 (Ang2)-functionalized lipid cubosomes loaded with cisplatin (CDDP) and temozolomide (TMZ) for crossing the BBB and providing targeted glioblastoma therapy. Developed lipid cubosomes showed a particle size of around 300 nm and possessed an internal ordered inverse primitive cubic phase, a high conjugation efficiency of Ang2 to the particle surface, and an encapsulation efficiency of more than 70% of CDDP and TMZ. In vitro models, including BBB hCMEC/D3 cell tight monolayer, 3D BBB cell spheroid, and microfluidic BBB/GBM-on-a-chip models with cocultured BBB and glioblastoma cells, were employed to study the efficiency of the developed cubosomes to cross the BBB and showed that Ang2-functionalized cubosomes can penetrate the BBB more effectively. Furthermore, Ang2-functionalized cubosomes showed significantly higher uptake by U87 glioblastoma cells, with a 3-fold increase observed in the BBB/GBM-on-a-chip model as compared to that of the bare cubosomes. Additionally, the in vivo biodistribution showed that Ang2 modification could significantly enhance the brain accumulation of cubosomes in comparison to that of non-functionalized particles. Moreover, CDDP-loaded Ang2-functionalized cubosomes presented an enhanced toxic effect on U87 spheroids. These findings suggest that the developed Ang2-cubosomes are prospective for improved BBB crossing and enhanced delivery of therapeutics to glioblastoma and are worth pursuing further as a potential application of nanomedicine for GBM treatment.

Development and Characterization of Sulfasalazine Cubosomes for Potential Transdermal Drug Delivery.

BACKGROUND: Rheumatoid arthritis is indeed a constant, progressive autoimmune disease that acts on the synovial membrane, distinguished by joint pain, swelling, and tenderness. Sulfasala- zine belongs to BCS Class IV having low solubility and low permeability. To overcome the issue and provide a localized effect Cubosomes were chosen for the transdermal drug delivery system. OBJECTIVE: The primary objective of this investigation was to pass on sulfasalazine-loaded cubo- somes over the skin to treat rheumatoid arthritis. On the way to overcome this issue of oral sulfasala- zine and provide localized effect, Cubosomes were chosen for the transdermal drug delivery system. METHODS: Sulfasalazine-loaded cubosomes were prepared by the top-down method using GMO and Poloxamer 407. Different concentrations of lipid and surfactant were used in the formulation using 32 full factorial designs. The prepared formulations were assessed for p.s, z,p, %EE, FTIR, SEM, in- vitro release, ex-vivo permeation, and deposition studies with pH 7.4 phosphate buffer saline. RESULTS: The particle size varies between 65 nm to 129 nm, while the negative zeta potential ranged from - 18.8 mV to -24.8 mV. The entrapment efficiency was between 87% and 95%. The formulations' in-vitro drug release was carried out for 12 hours. The optimized formulation showed a controlled release of sul- fasalazine and better ex-vivo permeation and deposition properties than sulfasalazine suspension. CONCLUSION: Overall study findings support the possibility of applying transdermal sulfasalazine- loaded cubosomes to alleviate rheumatoid arthritis.

Hesperidin-loaded cubogel as a novel therapeutic armamentarium for full-thickness wound healing.

Wounds are a physical manifestation of injury to the skin causing it to rupture or tear. The process of wound healing naturally restores skin integrity while minimizing the extent of the damage. Hesperidin (HPN) is a natural polyphenolic flavonoid and is effective in treating wounds due to its ability to reduce inflammation and stimulate angiogenesis. However, its use is limited by its poor physicochemical attributes such as poor solubility in water. Recently, nanoparticles, particularly Cubosomes, are found to be promising candidates for advancing wound-healing therapies, owing to their unique properties. The present study was conducted to develop a hydrogel system based on Cubosomes encapsulating HPN (HPN-Cubogel), with the potential to mitigate full-thickness wounds. The therapeutic efficacy of the formulation assessed in the animal model showed that the HPN-Cubogel formulation group exhibited a wound closure rate of 98.96 ± 1.50% after 14 days post-wounding compared to 89.12 ± 2.6% in the control group suggesting superior wound contraction activity. Collagen synthesis was superior in the formulation compared to the control group, as determined through MT staining. In summary, the HPN-Cubogel formulation was found to be the most effective in enhancing full-thickness wound healing.

A Synoptic Update on Smart Lipid Nanocarrier: Cubosomes, and their Design Development, and Recent Challenges.

Cubosomes are a kind of nanoparticle that is distinct from solid particles in that they are liquid crystalline particles formed by self-assembly of a certain surfactant with a current water ratio. Their unique properties as a result of their microstructure are useful in practical applications. Cubosomes, specifically lyotropic nonlamellar liquid crystalline nanoparticles (LCNs) have gained acceptance as a medication delivery strategy for cancer and other disorders. Cubosomes are produced by the fragmentation of a solid-like phase into smaller particles. Because of its particular microstructure, which is physiologically safe and capable of allowing for the controlled release of solubilized compounds, cubic phase particles are garnering considerable attention. These cubosomes are highly adaptable carriers with promising theranostic efficacy because they can be given orally, topically, or intravenously. Throughout its operation, the drug delivery system regulates the loaded anticancer bioactive's target selectivity and drug release characteristics. This compilation examines recent advances and obstacles in the development and application of cubosomes to treat various cancers, as well as the challenges of turning it into a potential nanotechnological invasion.

A comprehensive review on lipid nanocarrier systems for cancer treatment: fabrication, future prospects and clinical trials.

Over the last few decades, cancer has been considered a clinical challenge, being among the leading causes of mortality all over the world. Although many treatment approaches have been developed for cancer, chemotherapy is still the most utilized in the clinical setting. However, the available chemotherapeutics-based treatments have several caveats including their lack of specificity, adverse effects as well as cancer relapse and metastasis which mainly explains the low survival rate of patients. Lipid nanoparticles (LNPs) have been utilized as promising nanocarrier systems for chemotherapeutics to overcome the challenges of the currently applied therapeutic strategies for cancer treatment. Loading chemotherapeutic agent(s) into LNPs improves drug delivery at different aspects including specific targeting of tumours, and enhancing the bioavailability of drugs at the tumour site through selective release of their payload, thus reducing their undesired side effects on healthy cells. This review article delineates an overview of the clinical challenges in many cancer treatments as well as depicts the role of LNPs in achieving optimal therapeutic outcomes. Moreover, the review contains a comprehensive description of the many LNPs categories used as nanocarriers in cancer treatment to date, as well as the potential of LNPs for future applications in other areas of medicine and research.

Regulating the structural polymorphism and protein corona composition of phytantriol-based lipid nanoparticles using choline ionic liquids.

Lipid-based lyotropic liquid crystalline nanoparticles (LCNPs) face stability challenges in biological fluids during clinical translation. Ionic Liquids (ILs) have emerged as effective solvent additives for tuning the structure of LCNP's and enhancing their stability. We investigated the effect of a library of 21 choline-based biocompatible ILs with 9 amino acid anions as well as 10 other organic/inorganic anions during the preparation of phytantriol (PHY)-based LCNPs, followed by incubation in human serum and serum proteins. Small angle X-ray scattering (SAXS) results show that the phase behaviour of the LCNPs depends on the IL concentration and anion structure. Incubation with human serum led to a phase transition from the inverse bicontinuous cubic (Q2) to the inverse hexagonal (H2) mesophase, influenced by the specific IL present. Liquid chromatography-mass spectrometry (LC-MS) and proteomics analysis of selected samples, including PHY control and those with choline glutamate, choline hexanoate, and choline geranate, identified abundant proteins in the protein corona, including albumin, apolipoproteins, and serotransferrin. The composition of the protein corona varied among samples, shedding light on the intricate interplay between ILs, internal structure and surface chemistry of LCNPs, and biological fluids.

Cubosomal functionalized block copolymer platform for dual delivery of linagliptin and empagliflozin: Recent advances in synergistic strategies for maximizing control of high-risk type II diabetes.

A well-made chitosan-PVP block copolymer platform was equipped with highly ordered and uniform nano-channels. This highly adhesive block copolymer platform was designed to ensure the efficient co-delivery of two synergistic-acting hypoglycemic drugs. Linagliptin oral bioavailability is 30% due to poor permeability and intestinal degradation. Its pharmacokinetics shows a non-linear profile. Empagliflozin exhibited decreased permeability and decreased solubility in aqueous media between pH 1 and 7.5. Cubosomes were functionalized as a good microdomain to guest and improve the physicochemical characteristics of drug molecules with decreased permeability and solubility. Cubosomes loaded with linagliptin (linagliptin cubosomes (LCs)) and empagliflozin (empagliflozin cubosomes ECs) were separately prepared using the top-down method and optimized by applying 23 factorial design. Optimized cubosomal systems LCs (F3) and ECs (F4) were incorporated into a chitosan-PVP gel to obtain dual cubosome-loaded platforms (LECF) optimized through 22 factorial design. The permeation study from the optimized LECF (C1) ensured enhanced empagliflozin permeation alongside continued efflux for linagliptin, resolving potential risks due to its non-linear plasma profile. The in-vivo study revealed that AUC(0-∞) of linagliptin and empagliflozin was enhanced by 2- and threefold, respectively. Therefore, the chitosan-PVP block copolymer platform buccal application for the co-delivery of linagliptin and empagliflozin could contribute to enhanced clinical effectiveness in treating diabetes.

Novel dual targeting cubosomes modified with angiopep-2 for co-delivery GNA and PLHSpT to brain glioma.

3Glioblastoma multiforme is the most aggressive malignant brain tumor. However, the treatment of glioblastoma multiforme faces great challenges owing to difficult penetration of the blood-brain barrier. Therefore, more effective treatment strategies are desired quite urgently. In our study, a dual-targeting drug delivery system for co-loading with hydrophobic Gambogenic acid and hydrophilic PLHSpT was developed by cubosomes with angiopep-2 decorating. The Ang-cubs-(GNA + PLHSpT) was prepared by high-temperature emulsification-low-temperature solidification demonstrating excellent physical properties.Transmission electron microscopy revealed that Ang-cubs-(GNA + PLHSpT) was nearly spherical with a "core-shell" double-layer structure. Differential scanning calorimetry suggested that a new phase was formed. Small-angle X-ray scattering also verified that Ang-cubs-(GNA + PLHSpT) retains the Pn3m cubic. Moreover, laser confocal indicated that Ang-cubs-(GNA + PLHSpT) was capable of crossing BBB via binding to lipoprotein receptor-related protein-1, likely suggesting the potential tumor-specific targeting characteristic. Compared to free drug and cubs-(GNA + PLHSpT), Ang-cubs-(GNA + PLHSpT) was easily taken up by C6 cell and exhibited better anti-glioma effects in vitro. Importantly, GNA and PLHSpT co-loaded Ang-cubs could suppress tumor growth and significantly prolong survival in vivo. In conclusion, Ang-cubs-(GNA + PLHSpT) acts as a new dual-targeting drug delivery system for the treatment of GBM.