Phospholipon 90H Research Articles

Design and evaluation of nanostructured lipid carrier of Bergenin isolated from Pentaclethra macrophylla for anti-inflammatory effect on lipopolysaccharide-induced inflammatory responses in macrophages

Herein, we report the properties of nanostructured lipid carriers (NLCs) prepared with a gradient concentration of Bergenin (BGN) isolated from Pentaclethra macrophylla stem bark powder. A gradient concentration of BGN (BGN 0, 50, 100, 150, and 200 mg) was prepared in a 5 % lipid matrix consisting of Transcutol HP (75 %), Phospholipon 90H (15 %), and Gelucire 43/01 (10 %) to which a surfactant aqueous phase consisting of Tween 80, sorbitol, and sorbic acid was dissolved. The NLCs were evaluated by size, polydispersity index (PDI), zeta potential, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), encapsulation efficiency, and in vitro drug release. The result shows polydispersed nanoparticles with high drug encapsulation (94.26–99.50 %). The nanoparticles were mostly spherical, but those from the 50 mg BGN batch were more cuboidal than spherical. The drug release was highest from the latter to the tune of 40 % compared to the pure BGN solution, which released about 15 % BGN. The anti-inflammatory activity of the BGN-NLC and total plant extract was studied on lipopolysaccharide (LPS)-inflamed macrophages. The cell study showed that BGN and plant extract had low cytotoxicity on macrophages and exhibited a dose-dependent anti-inflammatory effect on the LPS-induced inflammatory process in macrophages.

Liposomes as selenium nanocarriers for foliar application to wheat plants: A biofortification strategy

In the present work, liposomes have been used as nanocarriers in the biofortification of wheat plants with selenium (Se) through foliar application. Liposomal formulations were prepared using 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and Phospholipon®90H (P90H) (average size <100 nm), loaded with different concentrations of inorganic Se (selenite and selenate) and applied twice to the plants in the stage of vegetative growth. Liposomes enhanced Se uptake by wheat plants compared to direct application. The highest Se enrichment was achieved using the phospholipid DPPC and a concentration of 1000 μmol·L−1 of Se without affecting the biomass, chlorophylls, carotenoids, and the concentration of mineral nutrients of the plants. The chemical speciation of Se in the plants was further investigated by X-ray absorption spectroscopy (XAS). The results from XAS spectra revealed that most of the inorganic Se was transformed to organic Se and that the use of liposomes influenced the proportion of C-Se-C over C-Se-Se-C species.

Synergistic approach for acne vulgaris treatment using glycerosomes loaded with lincomycin and lauric acid: Formulation, in silico, in vitro, LC-MS/MS skin deposition assay and in vivo evaluation

This study aims to develop a pharmaceutical formulation that combines the potent antibacterial effect of lincomycin and lauric acid against Cutibacterium acnes (C. acnes), a bacterium implicated in acne. The selection of lauric acid was based on an in silico study, which suggested that its interaction with specific protein targets of C. acnes may contribute to its synergistic antibacterial and anti-inflammatory effects. To achieve our aim, glycerosomes were fabricated with the incorporation of lauric acid as a main constituent of glycerosomes vesicular membrane along with cholesterol and phospholipon 90H, while lincomycin was entrapped within the aqueous cavities. Glycerol is expected to enhance the cutaneous absorption of the active moieties via hydrating the skin. Optimization of lincomycin-loaded glycerosomes (LM-GSs) was conducted using a mixed factorial experimental design. The optimized formulation; LM-GS4 composed of equal ratios of cholesterol:phospholipon90H:Lauric acid, demonstrated a size of 490 ± 17.5 nm, entrapment efficiency-values of 90 ± 1.4 % for lincomycin, and97 ± 0.2 % for lauric acid, and a surface charge of −30.2 ± 0.5mV. To facilitate its application on the skin, the optimized formulation was incorporated into a carbopol hydrogel. The formed hydrogel exhibited a pH value of 5.95 ± 0.03 characteristic of pH-balanced skincare and a shear-thinning non-Newtonian pseudoplastic flow. Skin deposition of lincomycin was assessed using an in-house developed and validated LC-MS/MS method employing gradient elution and electrospray ionization detection. Results revealed that LM-GS4 hydrogel exhibited a two-fold increase in skin deposition of lincomycin compared to lincomycin hydrogel, indicating improved skin penetration and sustained release. The synergistic healing effect of LM-GS4 was evidenced by a reduction in inflammation, bacterial load, and improved histopathological changes in an acne mouse model. In conclusion, the proposed formulation demonstrated promising potential as a topical treatment for acne. It effectively enhanced the cutaneous absorption of lincomycin, exhibited favorable physical properties, and synergistic antibacterial and healing effects. This study provides valuable insights for the development of an effective therapeutic approach for acne management.

Carvacrol-Loaded Phytosomes for Enhanced Wound Healing: Molecular Docking, Formulation, DoE-Aided Optimization, and in vitro/in vivo Evaluation.

Despite recent advances in wound healing products, phytochemicals have been considered promising and attractive alternatives. Carvacrol (CAR), a natural phenolic compound, has been reported to be effective in wound healing. This work endeavored to develop novel CAR-loaded phytosomes for the enhancement of the wound healing process. Molecular docking was performed to compare the affinities of the different types of phospholipids to CAR. Phytosomes were prepared by three methods (thin-film hydration, cosolvency, and salting out) using Lipoid S100 and Phospholipon 90H with three levels of saturation percent (0%, 50%, and 100%), and three levels of phospholipid molar percent (66.67%, 75%, and 80%). The optimization was performed using Design Expert where particle size, polydispersity index, and zeta potential were chosen as dependent variables. The optimized formula (F1) was further investigated regarding entrapment efficiency, TEM, 1H-NMR, FT-IR, DSC, X-RD, in vitro release, ex vivo permeation, and stability. Furthermore, it was incorporated into a hydrogel formulation, and an in vivo study was conducted to investigate the wound-healing properties of F1. F1 was chosen as the optimized formula prepared via the thin-film hydration method with a saturation percent and a phospholipid molar percent of zero and 66.67, respectively. TEM revealed the spherical shape of phytosomal vesicles with uniform size, while the results of 1H-NMR, FT-IR, DSC, and X-RD confirmed the formation of the phytosomal complex. F1 demonstrated a higher in vitro release and a slower permeation than free CAR. The wound area of F1-treated animals showed a marked reduction associated with a high degree of collagen fiber deposition and enhanced cellular proliferation. F1 can be considered as a promising remedy for the enhancement of wound healing and hence it would be hoped to undergo further investigation.

Budesonide-Loaded Bilosomes as a Targeted Delivery Therapeutic Approach Against Acute Lung Injury in Rats

Budesonide (BUD), a glucocorticoids drug, inhibits all steps in the inflammatory response. It can reduce and treat inflammation and other symptoms associated with acute lung injury such as COVID-19. Loading BUD into bilosomes could boost its therapeutic activity, and lessen its frequent administration and side effects. Different bilosomal formulations were prepared where the independent variables were lipid type (Cholesterol, Phospholipon 80H, L-alpha phosphatidylcholine, and Lipoid S45), bile salt type (Na cholate and Na deoxycholate), and drug concentration (10, 20 mg). The measured responses were: vesicle size, entrapment efficiency, and release efficiency. One optimum formulation (composed of cholesterol, Na cholate, and 10 mg of BUD) was selected and investigated for its anti-inflammatory efficacy in vivo using Wistar albino male rats. Randomly allocated rats were distributed into four groups: The first: normal control group and received intranasal saline, the second one acted as the acute lung injury model received intranasal single dose of 2 mg/kg potassium dichromate (PD). Whereas the third and fourth groups received the market product (Pulmicort® nebulising suspension 0.5 mg/ml) and the optimized formulation (0.5 mg/kg; intranasal) for 7 days after PD instillation, respectively. Results showed that the optimized formulation decreased the pro-inflammatory cytokines TNF-α, and TGF-β contents as well as reduced PKC content in lung. These findings suggest the potentiality of BUD-loaded bilosomes for the treatment of acute lung injury with the ability of inhibiting the pro-inflammatory cytokines induced COVID-19.

Phyto-emulsomes as a novel nano-carrier for morine hydrate to combat leukemia: In vitro and pharmacokinetic study

This study tackles the development of morin hydrate-loaded Phyto-Emulsomes (MH-EMs) using β-sitosterol as a ‘heart-friendly’ alternative to cholesterol for curing leukemia. β-sitosterol was isolated from the aerial parts of C. pallescens Delile (Compositae). Phyto-Emulsomes were prepared using different ratios of glyceryl monostearate (GMS), phospholipon 80H (P80H) and ß-sitosterol (SS), then, their size, entrapment efficiency, and drug release were evaluated. Among the prepared formulae, MH-EM5 composed of GMS: P80H: SS (2:0.5:0.5) had the highest drug release efficiency (RE = 82.28 ± 1.96%) and the smallest particle size (271.7 ± 4.86 nm) with a uniform distribution. MH-EM5 was subjected to characterization including the micro-morphological examination using TEM, thermal analysis, in addition to biological evaluation. The biostability of MH-EM5 in serum and bile salts was proved. The potential cytotoxicity of the free drug, MH-EM5 and its corresponding unmedicated formulation against normal oral epithelial cell and acute monocytic leukemia was studied. The results showed a negligible cytotoxicity in normal cells for all tested samples, while, cancer cells had a significant decrease in the cell viability in case of the selected formula (MH-EM5) compared to the corresponding unmedicated one as well as the free drug, at different concentrations up to 300 μg/ml. Also, the oral bioavailability study proved the significant increase of all measured pharmacokinetic parameters, after a single oral administration of MH-EM5 compared to the free drug suspension. Regarding these findings, phyto-emulsomes can be considered as a safe and promising nanometric delivery system for the oral administration of morin hydrate due to the enhancement of its solubility, oral bioavailability and antitumor efficacy.

Statistically designed novel ranolazine-loaded ethosomal transdermal gel for the treatment of angina pectoris

Ranolazine (RZ) is a newer novel anti-anginal drug with poor solubility and high permeability features. The current research work focused on the statistical design and development of RZ-loaded ethosome as a novel carrier through entrapment and in silico binding affinity studies using molecular docking. The study investigates the prospect of ethosomes as lipid nano-carrier in the form of vesicles for the transdermal enhancement of RZ. The affinity studies of RZ with Phospholipon 90H (PL90H) and a copolymer cholesterol signified the importance of cholesterol in the entrapment of drug in polar region of lipid bilayer in ethosomal vesicle with binding affinity −10.2 kcal/mol that enhanced drug solubility and absorption. In the absence of copolymer, the drug entrapped in non-polar tail with significantly less binding affinity −1.9 kcal/mol. Based on this finding the effective RZ-loaded ethosome compositions were designed and optimized. The Box-Behnken Design (BBD) was applied to fabricate ethosomes with changing amounts of phospholipon PL90H, hydroethanol, and cholesterol. The influence of independent variables PL90H (A), hydroethanol solution (B), and cholesterol (C) on vesicle size (nm), and % entrapment efficiency (%EE) was studied. The optimized ethosome formulation (R4) containing drug in ethosomal vesicle, evaluated using FTIR and XRD techniques, revealed a change in its physical state. Results demonstrated composition R4 with PL90H (100 mg) and hydroethanol (40% w/v) was embedded into Carbopol 934P gel to screen drug permeation and skin irritation. The ethosomal suspension (R4) was demonstrated with ethosome size 165.71 ± 2.73 nm, zeta potential −36.63 ± 2.78 mV, and %EE 80.21 ± 1.27. The optimized ethosomal suspension recorded release of RZ through dialysis membrane against RZ-loaded plain gel; was superior sustained over 24 h. The drug release from ethosomal gel followed a combination of Higuchi and Peppas model. RZ ethosomal gel tested using MTT assay manifested enhanced cytotoxic potential of RZ on H9C2-mouse cardiomyoblast cell line. Incorporation of vesicles into the gel leads to significant improvement in its stability. The present study demonstrates the prospective of ethosomal vesicles in delivering RZ across transdermal layers with the least skin irritation potential proclaiming its better safety, efficacy, and patient compliance.

Nanoencapsulation of Origanum vulgare essential oil into liposomes with anticancer potential.

Origanum vulgare L. essential oil possesses a wide spectrum of biological activities. Nanoencapsulation of O. vulgare essential oil into liposomes seems to be a promising strategy to maintain and improve these biological properties. This research was carried out to develop a suitable liposomal formulation for the effective encapsulation of O. vulgare essential oil in order to improve the antioxidant and cytotoxic activities. The characterization of liposomal nanocarriers was conducted in terms of size, zeta potential, and encapsulation efficiency. An MTT assay was used to assess the cytotoxic activity of the prepared and characterized O. vulgare essential oil liposomes in MCF-7 cancer cell lines. Antioxidant activity was determined by assessing DPPH scavenging activity. O. vulgare essential oil exerted cytotoxic activity with an IC50 of 50 μg/ml. The essential oil of O. vulgare was effectively encapsulated in liposomes, with no significant change observed among the formulations. The antioxidant activity was significantly enhanced after encapsulating the essential oil in liposomes. Origanum vulgare essential-oil-loaded Phospholipon 90H liposomes demonstrated considerably increased cytotoxic activity against MCF-7 cells, whereas Lipoid S100 liposomes showed no significant differences from the non-encapsulated essential oil. Phospholipon 85G liposomes had the least cytotoxic impact. As a result, liposomes containing O. vulgare essential oil may be promising nanocarriers for the development of anticancer agents.

Development of liposomal formulations of the eggplant glycoalkaloids solasonine and solamargine

The eggplant glycoalkaloids solasonine and solamargine are efficient biomacromolecules against skin diseases but are water-insoluble which results in inefficient treatment due to inadequate transdermal delivery. To address this problem, several liposomal formulations were prepared and evaluated for parameters including lecithin type, hydration temperature, and pH. The optimal formula with high physical and chemical stability included the lecithin Phospholipon 80H hydrated with 10 mM NaCl (pH 5.5). Solasonine - solamargine loaded liposomes were tested for their physical and chemical stability and drug leakage over a three-month period. Furthermore, the drug release profile of the loaded liposomes was evaluated with different release media. The glycoalkaloids and their liposomal formulations were assessed for their biological activity in culture using HaCaT and SCC-25 cell lines. This work resulted in a biologically effective liposomal formulation that was stable (size <220 nm, PDI <0.25, encapsulation efficiency >80%) for at least three months.

Formulation, Evaluation, and Optimization of Diacerein Loaded Transferosomal Gel for Arthritis

The objective of the current study was to develop and evaluate diacerein-loaded transferosomal gel to augment the permeation of diacerein into the deeper skin layer and finally to the affected area to treat arthritis. Preliminary studies included the process variable optimization (RPM) and selection of surfactant. The circumscribed central composite design was included to explore the reactions of the amount of phospholipon 90H, cholesterol, and span 60 on dependent variables like % entrapment co

Formulation Development and Evaluation of Itraconazole Loaded Invasomes Hydrogel

Topical drug administration is a localized drug delivery system anywhere in the body through ophthalmic, rectal, vaginal and skin as topical routes. Skin is one of the most readily accessible organs on human body for topical administration and is main route of topical drug delivery system. There are various skin infections caused by fungus. An antifungal medication is a pharmaceutical fungicide used to treat mycoses such as athlete’s foot ringworm, candidiasis. Antifungal works by exploiting differences between mammalian and fungal cells to kill the fungal organism without dangerous effect on host. Itraconazole (ITZ) is commonly used in the treatment of fungal infections. It has low bioavailability (55%) because of low aqueous solubility and first pass effect. Hence we attempted to develop Itraconazole-loaded invasomes hydrogel. ITZ-loaded invasomes were prepared by conventional thin layer evaporation technique using Phospholipon 90H, terpene (Limonene) and ethanol. The optimized ITZ-loaded invasomes was incorporated into carbopol 934p (0.5 to 2%) solution to get a hydrogel for improving convenience in superficial application. FT-IR studies revealed no interaction between the drug and excipients. The formulated hydrogel formulation was evaluated with parameter pH, viscosity, gel strength, drug content, spread ability, in-vitro release test, wash ability, extrudability study and stability studies. The formulation OIGF4 showed a drug content of 99.12% and drug release of 99.78% in 72 hrs, which contains carbopol 934p concentration 2%w/w. The present work also focuses on making the formulation more pharmaceutically acceptable.

Encapsulation of α-Pinene in Delivery Systems Based on Liposomes and Cyclodextrins.

The essential oil component α-pinene has multiple biological activities. However, its application is limited owing to its volatility, low aqueous solubility, and chemical instability. For the aim of improving its physicochemical properties, α-pinene was encapsulated in conventional liposomes (CLs) and drug-in-cyclodextrin-in-liposomes (DCLs). Hydroxypropyl-β-cyclodextrin/α-pinene (HP-β-CD/α-pinene) inclusion complexes were prepared in aqueous solution, and the optimal solubilization of α-pinene occurred at HP-β-CD:α-pinene molar ratio of 7.5:1. The ethanol-injection method was applied to produce different formulations using saturated (Phospholipon 90H) or unsaturated (Lipoid S100) phospholipids in combination with cholesterol. The size, the phospholipid and cholesterol incorporation rates, the encapsulation efficiency (EE), and the loading rate (LR) of α-pinene were determined, and the storage stability of liposomes was assessed. The results showed that α-pinene was efficiently entrapped in CLs and DCLs with high EE values. Moreover, Lipoid S100 CLs displayed the highest LR (22.9 ± 2.2%) of α-pinene compared to the other formulations. Both carrier systems HP-β-CD/α-pinene inclusion complex and Lipoid S100 CLs presented a gradual release of α-pinene. Furthermore, the DPPH radical scavenging activity of α-pinene was maintained upon encapsulation in Lipoid S100 CLs. Finally, it was found that all formulations were stable after three months of storage at 4 °C.

Quantitative structure property relationship assisted development of Fluocinolone acetonide loaded transfersomes for targeted delivery

Fluocinolone acetonide (FA) is a corticosteroid, synthetic hydrocortisone used to reduce skin inflammation and itching in psoriasis. The present study investigate the formulation of nanotransfersomes containing FA (FA-NTs) using Quantitative Structure Property Relationship (QSPR) and Box–Behnken approach. FA-NTs containing phospholipid, edge activator and cholesterol in definite ratio were prepared by high pressure homogenization and optimized using Box–Behnken design. Based on the QSPR analysis, Phospholipon 90H was selected for nanotransfersome form along with sodium deoxycholate as edge activator. The impact of independent variables Phospholipid concentration (X1), sodium deoxycholate (X2) and number of homogenization cycles (X3) on dependent variables viz., particle size and entrapment efficiency (%EE) were studied. The optimized nanotransfersomal formulation was characterized for FTIR, XRD, DSC, particle size, zeta potential, entrapment efficiency, in-vitro release and ex-vivo permeation studies. FA-NTs batch evidenced 92 ± 4% entrapment efficiency and showed 29.9 nm particle size, 0.264 polydispersity index and −23.72 mV zeta potential. FA-NTs exhibited 68% drug release within 24 h and followed Higuchi release kinetic model (R2 = 0.9902). FA-NTs showed 22.56 μg/cm2/h transdermal flux with 12.40 fold higher than FA dispersion. Biologically, FA-NTs showed hyperproliferation inhibition of differentiated HaCaT cells as evidenced from cell viability, antiproliferative action, nitric oxide production, proinflammatory cytokine measurement, Quantitative Real time PCR and cellular uptake studies. Thus, the present study demonstrates the successful use of QSPR studies and Box–Behnken design in the preparation of nanotransfersomes for efficient delivery of FA in the management of psoriasis.

Efavirenz Loaded Mixed Polymeric Micelles: Formulation, Optimization, and In Vitro Characterization.

Efavirenz (EFZ) is a biopharmaceutics classification system (BCS) Class-II, first-line antiretroviral (ARV) drug. However, its utility through the oral route is restricted by its poor solubility. The objective of this study was to formulate EFZ-loaded binary-mixed micelles as a potential carrier for oral administration of EFZ. Rubingh's regular solution theory was used to determine the interaction behavior of the two components (Cremophor RH 40 and Phospholipon 80H) and of the mixed micelles and synergistic behavior was confirmed. The mixed miceller system was formulated using solvent evaporation method and a 32 factorial design was used for the optimization of selected independent variables. Miceller systems were further characterized in terms of morphology, particle size, zeta potential, percent entrapment efficiency, and drug loading. Fourier transform infrared and differential scanning calorimetry measurements confirmed the entrapment of EFZ in the micelles. The optimized formulation presented desirable qualities viz., nanometric size (17.27 ± 0.079), high entrapment efficiency, and good colloidal stability. The prepared optimized micelles can be potential carriers for EFZ in ARV therapies.

QbD-driven development of dissolving microneedle patch loaded with ultradeformable liposomes encapsulated Noopept: Exploring a patient friendly, once-daily option to manage dementia

Noopept (NPT), a potent neuroprotective agent, suffers the problem of poor oral bioavailability (~10%) and thus demands exploration of ways of bioavailability improvement. Present work focuses on confronting this issue via development of NPT loaded ultradeformable liposomes (UDL) and its further incorporation in fast dissolving microneedle patch (MNP) for transdermal route. A combination of Phospholipon 90 G and Phospholipon 90H was used as bilayer forming lipids while sodium deoxycholate was used as edge activator to formulate NPT UDL by ethanol injection method. QbD approach was adapted to optimize NPT UDL considering vesicle size and entrapment efficiency as critical quality attributes (CQA). Fractional factorial design established amount of lipids, surfactant and NPT as critical material attributes and their optimum levels were statistically derived using combined D-optimal design. These optimized NPT UDL were fabricated as fast dissolving MNP and exhaustively evaluated to establish their safety, efficacy and stability. NPT UDL MNP possessed axial needle fracture force of 0.688 N which was sufficient enough to breach stratum corneum. Physical stability evaluation revealed that NPT UDL re-dispersion obtained from MNP matrix dissolution possessed identical vesicle shape and size while retaining > 99% NPT when compared to optimized NPT UDL. In vitro viability of HaCaT cells after exposure to NPT UDL MNP matrix was found to be 89.74% supporting the formulation as safe for transdermal application. NPT UDL MNP showed a 6.5-fold increase in steady state flux across full thickness pig ear skin as compared to NPT suspension. A 3-fold increase in relative bioavailability with similar pharmacological response as compared to oral NPT suspension was also observed during PK-PD studies in Sprague Dawley rats. Results were found fairly encouraging and created a scope of reducing both dose and dosing frequency to eventually improve the associated patient compliance.

Formulation and Optimization of Atovaquone Micronized Suspension by Top-down Method

Abstract: Aim: The present work aimed to tackle the solubility issue of a Biopharmaceutics Classification System (BCS) II drug, Atovaquone. Methods: Formulation of micronized suspension of atovaquone was optimized by employing a 32 full factorial design keeping poloxamer 188 (wetting agent) and phospholipon 90H (stabilizer) as the influential variables affecting the dependent variables viz. particle size and polydispersity index (PdI). Selected formulations from the optimized design space were further evaluated for dissolution and the formulation exhibiting maximum dissolution within 120 min was selected. The optimized batch consisting of atovaquone (15%), poloxamer 188 (2%), phospholipon 90H (1%), glycerin (10%) in the aqueous vehicle was microfluidized. Results: The particle size of resultant suspension was Zavg = 1313 ± 40 nm and PdI =0.1± 0.05. The zeta potential of the final micronized suspension was 0.0555 mV which indicated steric stabilization of the particles. The micronized suspension was adsorbed on a mixture of Kollidon CL SF and Aerosil 200 (2:1) and then dried and passed through 40# sieve. Conclusion: The solid-state characterization of the formulation revealed that the crystalline nature of the drug was retained after the milling process. The saturation solubility and in-vitro dissolution of adsorbed micronized suspension were 2.3-fold times enhanced as compared to the pure drug suspension due to a reduction in particle size. The top-down approach can be employed to improve the poor aqueous solubility of atovaquone. Key words: Atovaquone, Micronized suspension, Microfluidization, Full factorial design, Solubility enhancement.

Rutin-Loaded Solid Lipid Nanoparticles: Characterization and In Vitro Evaluation.

This study was aimed at preparing and characterizing solid lipid nanoparticles loading rutin (RT-SLNs) for the treatment of oxidative stress-induced diseases. Phospholipon 80H® as a solid lipid and Polysorbate 80 as surfactant were used for the SLNs preparation, using the solvent emulsification/diffusion method. We obtained spherical RT-SLNs with low sizes, ranging from 40 to 60 nm (hydrodynamic radius) for the SLNs prepared starting from 2% and 5% (w/w) theoretical amount. All prepared formulations showed negative zeta-potential values. RT was efficiently encapsulated within SLNs, obtaining high encapsulation efficiency and drug content percentages, particularly for SLNs prepared with a 5% theoretical amount of RT. In vitro release profiles and analysis of the obtained data applying different kinetic models revealed Fickian diffusion as the main mechanism of RT release from the SLNs. The morphology of RT-SLNs was characterized by scanning electron microscopy (SEM), whereas the interactions between RT and the lipid matrix were investigated by Raman spectroscopy, evidencing spectral modifications of characteristic bands of RT due to the establishment of new interactions. Finally, antioxidant activity assay on human glioblastoma astrocytoma (U373) culture cells showed a dose-dependent activity for RT-SLNs, particularly at the highest assayed dose (50 μM), whereas the free drug showed the lesser activity.

Design and development of terbinafine hydrochloride ethosomal gel for enhancement of transdermal delivery: In vitro, in vivo, molecular docking, and stability study

Terbinafine HCl (TH), an allylamine antifungal (BCS-II) drug has poor solubility and high permeability. In the present work, we have investigated the potential of ethosomes as vesicular lipid nanocarrier for enhancement of transdermal application of TH. The ethosomal formulation with varying concentrations of phospholipon 80H (PL80H) and the hydroethanolic solution was optimized and fabricated by applying a 32 full factorial design. The impact of independent variables PL80H (X1) and hydroethanolic solution (X2) on dependent variables viz., vesicle size (nm), zeta potential (mV), and entrapment efficiency (EE%) were studied. The formulation batch F8 with 100 mg phospholipon 80H (PL80H) and 40% w/v hydroethanolic was considered as most optimized amongst all the batches. The optimized TH ethosomes were embedded into 1% w/v Carbopol 934 gel to study drug release and skin interaction studies. The optimized formulation evidenced with vesicle size 127.39 ± 2.71 nm, zeta potential - 40.63 ± 2.77 mV and entrapment efficiency 87.55 ± 0.47%. The drug release from optimized ethosomal suspension through the cellophane membrane was much better sustained over 24 h compared to the marketed product. Additionally, the zone of inhibition of ethosomal gel against Aspergillus Bravia (fungal strain) was larger than the marketed product. We have also investigated the inhibitory potential of Terbinafine against squalene epoxidase of Aspergillus through molecular docking. The binding interactions have shown favorable results and explained the role of Terbinafine in fungus growth inhibition. The present study demonstrates that ethosomal vesicle has the potential to enhance transdermal delivery without any skin irritation. The TH loaded ethosomes could be one of the prominent approaches for transdermal application in the management of fungal diseases.

Solidified Reverse Micellar Solution-Based Lipid Microparticles of Miconazole Nitrate: Formulation Design, Biopharmaceutical Characterization, and Dissolution Studies

The present work was aimed at formulating solidified reverse micellar microparticles (SRMMs) using templated lipids (Softisan 154, stearic acid, and Phospholipon ®90H) for improved biopharmaceutical performance, dissolution of miconazole nitrate. SRMMs containing miconazole nitrate (MN) (1, 2, and 3% w/w) were formulated using Softisan® 154 (SOFT) and stearic acid (ST) and their combinations, containing Phospholipon® 90H (P90H) by melt homogenization employing Polysorbate 80 as the surfactant. The microparticles were freeze-dried, characterized, and optimized batches evaluated for in vitro dissolution in methanolic HCl and antifungal activity. The average SRMM yield was 70%. Entrapment efficiency and loading capacity determination showed that the lipid matrix composed of Softisan® 154 and Phospholipon® 90H (7:3) possessed greater entrapment than the other matrices with the 5% SOFT + P90H matrix containing 3% MN entrapping 98.48% of the drug. Preliminary anticandidal evaluation of the formulations showed significant activity of all the formulations containing drug. DSC analysis of the lipid excipients and matrices showed slight modifications in the physical nature of the excipients. Further analysis using X-ray diffraction showed retention of drug form in the formulations though with slight alterations in d-spacings of the X-ray diffractograms. In vitro dissolution studies of the optimized batches revealed a significant (p < 0.05) increase in dissolution rates of optimized SLM batches compared with pure MN. Kinetic modelling of the in vitro dissolution data revealed that most of the matrix systems evaluated best fitted the Korsenmeyer-Peppas model. SRMMs improved the in vitro dissolution and antifungal activity of MN.

Formulation and Evaluation of Novel Hybridized Nanovesicles for Enhancing Buccal Delivery of Ciclopirox Olamine.

Ciclopirox olamine (CPO) is a topical wide-spectrum antimycotic agent that possesses antifungal, antibacterial and anti-inflammatory activities. Loading CPO into a hybridized vesicular system is expected to enhance its buccal permeation and hence, therapeutic activity, whereas the frequent administration and side effects are reduced. Vesicular systems with high penetration ability were prepared based on cholesterol, Lipoid S45 or Phospholipon 90H, with span 60 while incorporating a penetration enhancer (Labrafac or labrasol) followed by full assessment of their size, entrapment efficiency, and drug release profiles. The optimum formulation, composed of Lipoid S45 and Labrafac, possessed the smallest vesicle size (346.1nm), highest entrapment efficiency (94.4%), and sustained CPO release pattern, and was characterized for its morphology and thermal properties. This powerful mixture of the penetration enhancers (Lipoid S45 and Labrafac) in the designed hybridized vesicles was thoroughly investigated for their characteristics after being incorporated in bioadhesive gel. Moreover, enhanced antifungal activity was demonstrated either upon testing the designed formulation on agar plates or in vivo upon treating infected rabbits with the proposed formulation. Results suggest that the presented bioadhesive gel incorporating the CPO-loaded vesicles can be a promising delivery system that can offer a prolonged localized antifungal treatment with enhanced therapeutic effect.