Hyaluronate functionalized Span-Labrasol nanovesicular transdermal therapeutic system of ferulic acid targeting diabetic nephropathy.

Diabetic kidney disease, known as diabetic nephropathy (DN), is a widespread severe diabetes complication leading to kidney failure. Due to the lack of efficacious therapies, this study endeavors to enhance DN therapeutic effectiveness of ferulic acid (FRA), a natural phenolic with poor oral bioavailability, by developing a transdermal kidney-targeted spanlastic formulation. Spanlastics (SP) nanovesicles were prepared using Span 60 and Labrasol or Brij35 as edge activators (EA). Cationic guar (CG) and hyaluronic acid (HA) were employed as coatings. The formulations were assessed for entrapment efficiency (EE), particle size (PS) and zeta potential (ZP). A 21 × 31 factorial optimization of FRA spanlastic formulations revealed the desirable nanoformula was FRA-L-H-SP comprising Labrasol and hyaluronate coating. Transmission electron microscopy (TEM), Fourier-transform infrared (FT-IR), Diphenylpicrylhydrazyl (DPPH) antioxidant activity, in-vitro release, and rat skin ex-vivo permeation assessed this formula and the uncoated one (FRA-L-SP). Biochemical indicators and histopathology for diabetes and kidney injury were evaluated in the Streptozotocin (STZ)-induced DN rat model. Results showed significant improvements after treatment with FRA-L-H-SP compared to FRA-L-SP and free FRA, with decreased blood glucose, creatinine, and intercellular adhesion molecule-1 (ICAM-1) levels and increased insulin, AMP-activated protein kinase (AMPK), and sirtuins (SIRT). This enhancement can be acknowledged as passive targeting of SP and active targeting properties of hyaluronic to cluster of differentiation 44 (CD44) receptors, revealing the potential to improve DN pathophysiology.

Green preparation and evaluation of the anti-psoriatic activity of vesicular elastic nanocarriers of kojic acid from Aspergillus oryzae N12: Repurposing of a dermo-cosmetic lead.

Psoriasis is a skin disorder characterized by impaired epidermal differentiation that is regularly treated by systemic drugs with undesirable side effects. Based on its anti-inflammatory, antiproliferative and anti-melanoma attributes, the fungal metabolite kojic acid represents an attractive candidate for anti-psoriatic research. The present work aims to investigate an efficient topical bio-friendly vesicular system loaded with kojic acid isolated from Aspergillus oryzae as an alternative way for the management of psoriasis to avoid systemic toxicity. Kojic acid-loaded spanlastics were prepared by ethanol injection technique, employing span 60 along with brij 35 and cremophor rh40 as edge activators, with the complete in vitro characterization of the developed nanoplatform. The selected formulation displayed a spherical morphology, an optimum particle size of 234.2 ± 1.65 nm, high entrapment efficiency (87.4% ± 0.84%) and significant sustained drug release compared with the drug solution. In vivo studies highlighted the superior relief of psoriasis symptoms and the ability to maintain healthy skin with the least changes in mRNA expression of inflammatory cytokines, achieved by the developed nanoplatform compared to kojic acid solution. Moreover, the in vivo histopathological studies confirmed the safety of the topically applied spanlastics. In addition, the molecular mechanism was approached through in vitro assessment of cathepsin S and PDE-4 inhibitory activities and in silico investigation of kojic acid docking in several anti-psoriatic drug targets. Our results suggest that a topically applied vesicular system loaded with kojic acid could lead to an expansion in the dermo-cosmetic use of kojic acid as a natural bio-friendly alternative for systemic anti-psoriatic drugs.

Overview of Spanlastics: A Groundbreaking Elastic Medication Delivery Device with Versatile Prospects for Administration via Various Routes.

When compared to the challenges associated with traditional dosage forms, medication delivery systems based on nanotechnology have been a huge boon. One such candidate for medication delivery is spanlastics, an elastic nanovesicle that can transport a diverse array of medicinal compounds. The use of spanlastics has been associated with an increase in interest in alternative administration methods. The non-ionic surfactant or surfactant blend is the main component of spanlastics. The purpose of this review was primarily to examine the potential of spanlastics as a delivery system for a variety of medication classes administered via diverse routes. Science Direct, Google Scholar, and Pubmed were utilized to search the academic literature for this review. Several studies have demonstrated that spanlastics greatly improve therapeutic effectiveness, increase medication absorption, and decrease drug toxicity. This paper provides a summary of the composition and structure of spanlastics along with their utility in the delivery of various therapeutic agents by adopting different routes. Additionally, it provides an overview of the numerous disorders that may be treated using drugs that are contained in spanlastic vesicles.

Repurposing of Nano-Engineered Piroxicam as an Approach for Cutaneous Wound Healing.

Drug repurposing is a potential strategy to overcome the huge economic expenses of wound healing products. This work aims to develop a topical gel of piroxicam encapsulated into a nanospanlastics vesicular system as an effective, dermal wound dressing. Firstly, piroxicam was entrapped into nanospanlastics formulations and optimized utilizing 23 full factorial experimental designs. The scrutinized factors were Span 60: Edge activator ratio, edge activator type, and permeation enhancer type. The measured responses were vesicle size (VS), polydispersity index (PDI), and% entrapment efficiency (EE). The optimized formula was further adopted into an alginate-pectin gel matrix to maximize adherence to the skin. The rheology and in-vitro release were studied for the developed nanospanlastics gel. Cytotoxicity and wound healing potential using scratch assay were assessed on human adult dermal fibroblast cells. The optimal piroxicam nanospanlastics formula demonstrated a VS of 124.1 ± 1.3 nm, PDI of 0.21 ± 0.01, and EE% of 97.27±0.21%. About 70.0 ± 0.9% and 57.4 ± 0.1% of piroxicam were released from nanospanlastics dispersion and gel within 24 h, respectively. Nanospanlastics gel of piroxicam flowed in a non-Newtonian pseudoplastic shear thinning pattern. It was also biocompatible with the human dermal fibroblast cells and significantly promoted their migration rate which suggests an auspicious cutaneous wound healing aptitude.

Non-pigmented laser hair removal mediated via sepia melanin nanoparticles: in vivo study on albino mice.

OBJECTIVES: Melanin is considered the main chromophore for laser hair removal. Due to a lack of laser-absorbing chromophores, removing non-pigmented hair with laser is quite problematic with unsatisfactory outcomes. This problem could be solved by delivering more melanin to the area around the hair follicle and enhancing that area as a target for light absorption. The insolubility of Sepia melanin as an exogenous dye, in most solvents, limits its bioavailability and thus its clinical use. METHODS: In our study, to overcome the solubility problems and increase the bioavailability of melanin for biomedical and cosmetic applications, natural sepia melanin was loaded in different nano-delivery systems (spanlastics and transfersomes) to be delivered to the hair follicles. The different formulations of melanin were prepared and characterized. In vivo skin deposition and histopathological studies were conducted on albino mice. RESULTS: Transmission electron microscopy (TEM) showed the spherical shape of the prepared vesicles with an average particle size of 252 and 262 nm and zeta potential of -22.5 and -35 mV for melanin spanlastics and melanin transfersomes, respectively. Histopathological examination of hair follicles and pilosebaceous glands for the irradiated and non-irradiated albino mice skin was studied post the application of the prepared formulations topically and subcutaneously. Qualitative statistical analysis was conducted and melanin transfersomes and melanin spanlastics showed significant damage to pilosebaceous glands and hair follicles with a p-value of 0.031 and 0.009 respectively. CONCLUSION: Melanin nanovesicles as transfersomes and spanlastics could be considered a promising approach for the removal of non-pigmented hair.

Spanlastic-laden nanogel as a plausible platform for dermal delivery of bimatoprost with superior cutaneous deposition and hair regrowth efficiency in androgenic alopecia.

Bimatoprost (BIM) is a prostaglandin F2α analogs originally approved for the treatment of glaucoma and ocular hypertension. Recent studies have highlighted its potential to boost hair growth. The objective of this investigation is to challenge the potential of spanlastics (SLs) as a surfactant-based vesicular system for promoting the cutaneous delivery of BIM for the management of alopecia. BIM-loaded spanlastics (BIM-SLs), composed of Span as the main vesicle component and Tween as the edge activator, were fabricated by ethanol injection method. The formulated BIM-SLs were optimized by 23 full factorial design. The optimized formula (F1) was characterized for entrapment efficiency, surface charge, vesicle size, and drug release after 12 h (Q12h). The optimized formula (F1) exhibited high drug entrapment efficiency (83.1 ± 2.1%), appropriate zeta potential (-19.9 ± 2.1 mV), Q12h of 71.3 ± 5.3%, and a vesicle size of 364.2 ± 15.8 nm, which favored their cutaneous accumulation. In addition, ex-vivo skin deposition studies revealed that entrapping BIM within spanlastic-based nanogel (BIM-SLG) augmented the dermal deposition of BIM, compared to naïve BIM gel. Furthermore, in vivo studies verified the efficacy of spanlastic vesicles to boost the cutaneous accumulation of BIM compared to naive BIM gel; the AUC0-12h of BIM-SLG was 888.05 ± 72.31 µg/mL.h, which was twice as high as that of naïve BIM gel (AUC0-12h 382.86 ± 41.12 µg/mL.h). Intriguingly, BIM-SLG outperforms both naïve BIM gel and commercial minoxidil formulations in stimulating hair regrowth in an androgenetic alopecia mouse model. Collectively, spanlastic vesicles might be a potential platform for promoting the dermal delivery of BIM in managing alopecia.

Unveiling Spanlastics as a Novel Carrier for Drug Delivery: A Review.

Innovative colloidal preparations that can alter the pharmacological properties of drugs have been made possible by the advancement of nanotechnology. Recent advances in the sciences of the nanoscale have led to the creation of new methods for treating illnesses. Developments in nanotechnology may lessen the side effects of medicine by using effective and regulated drug delivery methods. A promising drug delivery vehicle is spanlastics, an elastic nanovesicle that can transport a variety of drug compounds. Spanlastics have expanded the growing interest in many types of administrative pathways. Using this special type of vesicular carriers, medications intended for topical, nasal, ocular, and trans-ungual treatments are delivered to specific areas. Their elastic and malleable structure allows them to fit into skin pores, making them ideal for transdermal distribution. Spanlastic is composed of non-ionic surfactants or combinations of surfactants. Numerous studies have demonstrated how spanlastics significantly improve, drug bioavailability, therapeutic effectiveness, and reduce medication toxicity. The several vesicular systems, composition and structure of spanlastics, benefits of spanlastics over alternative drug delivery methods, and the process of drug penetration via skin are all summarized in this paper. Additionally, it provides an overview of the many medications that may be treated using spanlastic vesicles. The primary benefits of these formulations were associated with their surface properties, as a variety of proteins might be linked to the look. For instance, procedure assessment and gold nanoparticles were employed as biomarkers for different biomolecules, which included tumor label detection. Anticipate further advancements in the customization and combining of spanlastic vesicles with appropriate zeta potential to transport therapeutic compounds to specific areas for enhanced disease treatment.

Development of Carvedilol Nanoformulation-Loaded Poloxamer-Based In Situ Gel for the Management of Glaucoma.

The objective of the current study was to fabricate a thermosensitive in situ gelling system for the ocular delivery of carvedilol-loaded spanlastics (CRV-SPLs). In situ gel formulations were prepared using poloxamer analogs by a cold method and was further laden with carvedilol-loaded spanlastics to boost the precorneal retention of the drug. The gelation capacity, rheological characteristics, muco-adhesion force and in vitro release of various in situ gel formulations (CS-ISGs) were studied. The optimized formula (F2) obtained at 22% w/v poloxamer 407 and 5% w/v poloxamer 188 was found to have good gelation capacity at body temperature with acceptable muco-adhesion properties, appropriate viscosity at 25 °C that would ease its ocular application, and relatively higher viscosity at 37 °C that promoted prolonged ocular residence of the formulation post eye instillation and displayed a sustained in vitro drug release pattern. Ex vivo transcorneal penetration studies through excised rabbit cornea revealed that F2 elicited a remarkable (p ˂ 0.05) improvement in CRV apparent permeation coefficient (Papp = 6.39 × 10-6 cm/s) compared to plain carvedilol-loaded in situ gel (CRV-ISG; Papp = 2.67 × 10-6 cm/s). Most importantly, in normal rabbits, the optimized formula (F2) resulted in a sustained intraocular pressure reduction and a significant enhancement in the ocular bioavailability of carvedilol, as manifested by a 2-fold increase in the AUC0-6h of CRV in the aqueous humor, compared to plain CRV-ISG formulation. To sum up, the developed thermosensitive in situ gelling system might represent a plausible carrier for ophthalmic drug delivery for better management of glaucoma.

Spanlastics: a novel elastic drug delivery system with potential applications via multifarious routes of administration.

Drug delivery systems (DDS) based on nanocarriers are designed to transport therapeutic agents to specific areas of the body where they are required to exhibit pharmacodynamic effect. These agents rely on an appropriate carrier to protect them from rapid degradation or clearance and enhance their concentration in target tissues. Spanlastics, an elastic, deformable surfactant-based nanovesicles have the potential to be used as a drug delivery vehicle for wide array of drug molecules. Spanlastics are formed by the self-association of non-ionic surfactants and edge activators in an aqueous phase and have gained attention as promising drug carriers due to their biodegradable, biocompatible, and non-immunogenic structure. In recent years, numerous scientific journals have published research articles exploring the potential of spanlastics to serve as a DDS for various types of drugs as they offer targeted delivery and regulated release of the drugs. Following brief introduction to spanlastics, their structure and methods of preparation, this review focuses on the delivery of various drugs using spanlastics as a carrier via various routes viz. topical, transdermal, ototopical, ocular, oral and nasal. Work carried out by various researchers by employing spanlastics as a carrier for enhancing therapeutic activity of different moieties has been discussed in detail.

Enhancing the anticancer potential of metformin: fabrication of efficient nanospanlastics, in vitro cytotoxic studies on HEP-2 cells and reactome enhanced pathway analysis.

Metformin (MET), an oral antidiabetic drug, was reported to possess promising anticancer effects. We hypothesized that MET encapsulation in unique nanospanlastics would enhance its anticancer potential against HEP-2 cells. Our results showed the successful fabrication of Nano-MET spanlastics (d = 232.10 ± 0.20 nm; PDI = 0.25 ± 0.11; zeta potential = (-) 44.50 ± 0.96; drug content = 99.90 ± 0.11 and entrapment efficiency = 88.01 ± 2.50%). MTT assay revealed the enhanced Nano-MET cytotoxicity over MET with a calculated IC50 of 50 µg/mL and > 500 µg/mL, respectively. Annexin V/PI apoptosis assay showed that Nano-MET significantly decreased the percentage of live cells from 95.49 to 93.70 compared to MET and increased the percentage of cells arrested in the G0/G1 phase by 8.38%. Moreover, Nano-MET downregulated BCL-2 and upregulated BAX protein levels by 1.57 and 1.88 folds, respectively. RT-qPCR revealed that Nano-MET caused a significant 13.75, 4.15, and 2.23-fold increase in caspase-3, -8, and - 9 levels as well as a 100 and 43.47-fold decrease in cyclin D1 and mTOR levels, respectively. The proliferation marker Ki67 immunofluorescent staining revealed a 3-fold decrease in positive cells in Nano-MET compared to the control. Utilizing the combined Pathway-Enrichment Analysis (PEA) and Reactome analysis indicated high enrichment of certain pathways including nucleotides metabolism, Nudix-type hydrolase enzymes, carbon dioxide hydration, hemostasis, and the innate immune system. In summary, our results confirm MET cytotoxicity enhancement by its encapsulation in nanospanlastics. We also highlight, using PEA, that MET can modulate multiple pathways implicated in carcinogenesis.

Challenges and Opportunities for Celecoxib Repurposing.

Drug repositioning, also known as drug repurposing, reprofiling, or rediscovery, is considered to be one of the most promising strategies to accelerate the development of new original drug products. Multiple examples of successful rediscovery or therapeutic switching of old molecules that did not show clinical benefits or safety in initial trials encourage the following of the discovery of new therapeutic pathways for them. This review summarizes the efforts that have been made, mostly over the last decade, to identify new therapeutic targets for celecoxib. To achieve this goal, records gathered in MEDLINE PubMed and Scopus databases along with the registry of clinical trials by the US National Library of Medicine at the U.S. National Institutes of Health were explored. Since celecoxib is a non-steroidal anti-inflammatory drug that represents the class of selective COX-2 inhibitors (coxibs), its clinical potential in metronomic cancer therapy, the treatment of mental disorders, or infectious diseases has been discussed. In the end, the perspective of a formulator, facing various challenges related to unfavorable physicochemical properties of celecoxib upon the development of new oral dosage forms, long-acting injectables, and topical formulations, including the latest trends in the pharmaceutical technology, such as the application of mesoporous carriers, biodegradable microparticles, lipid-based nanosystems, or spanlastics, was presented.

Optimization of topical curcumin spanlastics for melanoma treatment.

The aim of the study was to enhance curcumin skin permeability through the preparation of spanlastics. Spanlastics were prepared using the ethanol injection technique through a central composite design using Span 60 concentration (X1), edge activator type (X2), and its concentration (X3) as the independent variables. The spanlastics were characterized for particle size (PS), encapsulation efficiency (EE), and dissolution efficiency (%DE24h). Formulae with the highest desirability (FN1 and FN2) were prepared and further characterized. They were elastic, spherical, nonirritant, and compatible with the used excipients. They had particle sizes of 147 and 198 nm, encapsulation efficiencies of 84.00% and 89.63%, zeta potential values of -45.50 and -39.10 mV, permeation enhancement ratios of 11.51 and 8.34 folds, and amounts retained of 7.25 and 10.44 µg/cm2 after 24 h, respectively. Formulae FN1 and FN2 showed cytotoxic effects after 48 h on human melanoma A375 with IC50 of 10.9 and 75.6 µg/mL, respectively. They increased the apoptotic effect confirming the success of the spanlastics to be a potential delivery for melanoma treatment.

Spanlastics as a Potential Approach for Enhancing the Nose-To-Brain Delivery of Piperine: In Vitro Prospect and In Vivo Therapeutic Efficacy for the Management of Epilepsy.

The present study delineates the preparation of piperine-loaded spanlastics (PIP-SPL) to improve piperine (PIP) solubility, bioavailability, and permeation through nasal mucosa for intranasal delivery. PIP-SPL was formulated using the thin-film hydration method and optimization was performed using Box-Behnken design (BBD). PIP-SPL optimized formulation (PIP-SPLopt) was characterized for polydispersity index (PDI), vesicle size, entrapment efficiency, zeta potential, and in vitro PIP release. For further evaluation, blood-brain distribution study, transmission electron microscopy (TEM), nasal permeation study, and confocal scanning laser microscopy (CLSM) were performed withal. The PIP-SPLopt presented spherical and sealed shape vesicles with a small vesicle size of 152.4 nm, entrapment efficiency of 72.93%, PDI of 0.1118, and in vitro release of 82.32%. The CLSM study unveiled that the developed formulation has greater permeation of PIP across the nasal mucosa in comparison with the PIP suspension. The blood-brain distribution study demonstrated higher Cmax and AUC0-24h of PIP-SPL via the intranasal route in comparison to PIP-SPL via oral administration. The in vivo study revealed that the PIP-SPL has good antiepileptic potential in comparison with the standard diazepam, which was evinced by seizure activity, neuromuscular coordination by rotarod test, biochemical estimation of oxidative stress markers, and histopathological studies. Furthermore, nasal toxicity study confirm that the developed PIP-SPL formulation is safer for intranasal application. The current investigation corroborated that the prepared spanlastic vesicle formulation is a treasured carrier for the PIP intranasal delivery for the management of epilepsy.

Diterpenoids profile of the marine sponge Chelonaplysilla erecta and candidacy as potential antitumor drugs investigated by molecular docking and pharmacokinetic studies.

The Chelonaplysilla genus possesses a numerous bioactive diterpenes with anti-inflammatory and cytotoxic effects. The current study aimed to assess the chemical composition of C. erecta crude extract (CECE) based on its metabolomic profile that has been integrated with neural network-based virtual screening and molecular docking using liquid chromatography with high resolution mass spectrometry (LCHR-MS). In addition to the estimation of the antitumor activity of the same extract via anti-interleukin-17A (IL-17) action, along with its formulated spanlastics preparation. The CECE markedly displayed growth inhibition for HepG-2 cells at IC50 value 16.5 ± 0.8 µg/mL, whereas the spanlastic formulation revealed more eminent antitumor effect against Caco-2 cells (IC50 = 2.8 ± 0.03 µg/mL). Among the dereplicated compounds, macfarlandin F (16) and pourewanone (25) demonstrated the highest potential with co-crystallized ligand 63 O within the active site of IL-17A in molecular docking studies. These findings rationalized the antitumor mechanism of marine organism for future chemotherapeutic applications.

Novel Luliconazole Spanlastic Nanocarriers: Development and Characterisation.

BACKGROUND: The formulation of spanlastic vesicles of luliconazole can be used to overcome its poor skin permeation and improve its antifungal efficacy. OBJECTIVE: In this study, we aimed to enhance the dermal delivery of luliconazole, an antifungal drug, through spanlastic vesicles. METHODS: A 23 regular factorial design was employed, using the Design Expert® software for optimization. The independent variables chosen were Span: Edge activator ratio, type of edge activator, and sonication intensity and their effect on the dependent variables, i.e., entrapment efficiency, particle size, and percentage of drug release after 8h were determined. Spanlastics were formulated by ethanol injection method using Tween 80 as an edge activator. RESULTS: Spanlastics were found to possess sizes in the nano range with entrapment efficiencies between 77 - 88% with optimum zeta potential and polydispersity index indicating a stable formulation. Differential scanning calorimetry, X-ray diffraction, and Fourier transform infrared studies revealed complete encapsulation of the drug within the elastic carriers. The optimized spanlastic formulation was further incorporated into a gel base and was found to be sufficiently viscous, spreadable, homogenous, showed a prolonged release for up to 8h and was also found to be non-irritant. The in-vitro permeation study revealed that the flux value obtained for luliconazole entrapped in the vesicular spanlastics (0.2292 mg/cm2.h) was also found to be higher than that of the marketed (0.1302 mg/cm2.h) and conventional gel (0.1122 mg/cm2.h). The optimized gel formulation was also evaluated for its antimycotic activity. Moreover, the optimized gel formulation also possessed a greater antimycotic activity against Candida albicans. The spanlastics loaded hydrogel formulation was found to have a greater zone of inhibition in comparison to the marketed formulation, thus proving to have optimum antifungal activity against Candida albicans. CONCLUSION: Collectively, the results revealed that spanlastics could be a potential nanocarrier for wellcontrolled delivery and for targeting deeper skin layers, thus providing new opportunities for dermal treatment.

Spanlastics gel-A novel drug carrier for transdermal delivery of glimepiride.

Glimepiride (3rd-generation sulfonylurea) is used for treatment of type 2 diabetes, but its oral administration has been associated with severe gastric disturbances such as nausea, vomiting, heartburn, anorexia, haemolytic anaemia. Accordingly, the transdermal route may represent a potentially suitable alternative. This work investigates the usefulness of a novel drug carrier system for transdermal application. The system investigated were called spanlastics gels and constituted span 60 with edge activator (tween 60 or tween 80). Spanlastics gel has been introduced as a stable form alternative to the liquid formulations of spanlastics. Spanlastics gels were prepared by coacervation phase separation method. Entrapment efficiency and size of spanlastics vesicles produced from the hydration of spanlastics gels were characterised. In vitro release and skin permeation of glimepiride from various spanlastics gel formulations were investigated across mixed cellulose membrane and excised rabbit skin. The obtained results indicated that the maximum entrapment efficiency was 65.36% when the tween 60 content was 30%. The drug release and permeation were increase as the concentration of edge activator increased. Spanlastics gel prepared with Tween 80 at concentration 50% showed higher permeability and flux value (248.69 µg/cm2and 8.31 µg/cm2.h, respectively) through rabbit skin.

Thin film hydration versus modified spraying technique to fabricate intranasal spanlastic nanovesicles for rasagiline mesylate brain delivery: Characterization, statistical optimization, and in vivo pharmacokinetic evaluation.

Rasagiline mesylate (RM) is a monoamine oxidase inhibitor that is commonly used to alleviate the symptoms of Parkinson's disease. However, it suffers from low oral bioavailability due to its extensive hepatic metabolism in addition to its hydrophilic nature which limits its ability to pass through the blood-brain barrier (BBB) and reach the central nervous system where it exerts its pharmacological effect. Thus, this study aims to form RM-loaded spanlastic vesicles for intranasal (IN) administration to overcome its hepatic metabolism and permit its direct delivery to the brain. RM-loaded spanlastics were prepared using thin film hydration (TFH) and modified spraying technique (MST). A 23 factorial design was constructed to study and optimize the effects of the independent formulation variables, namely, Span type, Span: Brij 35 ratio, and sonication time on the vesiclesá¾½ characteristics in each preparation technique. The optimized system prepared using MST (MST 2) has shown higher desirability factor with smaller PS and higher EE%; thus, it was selected for further in vivo evaluation where it revealed that the extent of RM distribution from the intranasally administered spanlastics to the brain was comparable to that of the IV drug solution with significantly high brain-targeting efficiency (458.47%). These results suggest that the IN administration of the optimized RM-loaded spanlastics could be a promising, non-invasive alternative for the efficient delivery of RM to brain tissues to exert its pharmacological activities without being dissipated to other body organs which subsequently may result in higher pharmacological efficiency and better safety profile.

Formulation and characterization of lamotrigine nasal insert targeted brain for enhanced epilepsy treatment.

Lamotrigine. (LMT) is a triazine drug has an antiepileptic effect but with low water solubility, dissolution rate and thus therapeutic effect. Spanlastics are nano-vesicular carriers' act as site-specific drug delivery system. Intranasal route could direct the drug from nose to brain and provide a faster and more specific therapeutic effect. Therefore, this study aimed to upload lamotrigine onto nano-vesicles using spanlastic nasal insert delivery for effective epilepsy treatment via overcoming lamotrigine's low solubility and improving its bioavailability. Lamtrigine-loaded nano-spanlastic vesicles were prepared by ethanol injection method. To study different formulation factor's effect on formulations characters; particle size (PS), Zeta potential (ZP), polydispersity index (PDI), entrapment efficiency percentage (EE%) and LMT released amount after 6 h (Q6h); 2^1 and 3^1 full factorial designs were employed. Optimized formula was loaded in lyophilized nasal inserts formulation which were characterized for LMT release and mucoadhesion. Pharmacokinetics studies in plasma and brain were performed on rats to investigate drug targeting efficiency. The optimal nano-spanlastic formulation (F4; containing equal Span 60 amount (100 mg) and edge activator; Tween 80) exhibited nano PS (174.2 nm), high EE% (92.75%), and Q6h > 80%. The prepared nasal inserts (S4) containing 100 mg HPMC has a higher mucoadhesive force (9319.5 dyne/cm2) and dissolution rate (> 80% within 10 min) for rapid in vivo bio-distribution. In vivo studies showed considerable improvement brain and plasma's rate and extent absorption after intranasal administration indicating a high brain targeting efficiency. The results achieved indicate that nano-spanlastic nasal-inserts offer a promising LMT brain targeting in order to maximize its antiepileptic effect.

Spanlastics as a Potential Platform for Enhancing the Brain Delivery of Flibanserin: In Vitro Response-Surface Optimization and In Vivo Pharmacokinetics Assessment.

Flibanserin was licensed by the United States Food and Drug Administration (FDA) as an oral non-hormonal therapy for pre-menopausal women with inhibited sexual desire disorder. However, it suffers from susceptibility to first-pass metabolism in the liver, low aqueous solubility, and degradation in the acidic stomach environment. Such hurdles result in a limited oral bioavailability of 33%. Thus, the aim of the study was to utilize the principles of nanotechnology and the benefits of an intranasal route of administration to develop a formulation that could bypass these drawbacks. A response-surface randomized D-optimal strategy was used for the formulation of flibanserin spanlastics (SPLs) with reduced size and increased absolute zeta potential. Two numerical factors were studied, namely the Span 60: edge activator ratio (w/w) and sonication time (min), in addition to one categorical factor that deals with the type of edge activator. Particle size (nm) and zeta potential (mV) were studied as responses. A mathematical optimization method was implemented for predicting the optimized levels of the variables. The optimized formulation was prepared using a Span: sodium deoxycholate ratio of 8:2 w/w; a sonication time of 5 min showed particle sizes of 129.70 nm and a zeta potential of -33.17 mV. Further in vivo assessment following intranasal administration in rats showed boosted plasma and brain levels, with 2.11- and 2.23-fold increases (respectively) compared to raw FLB. The aforementioned results imply that the proposed spanlastics could be regarded as efficient drug carriers for the trans-nasal delivery of drugs to the brain.