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This study aims to formulate a buccal mucoadhesive gel containing prednisolone sodium metazoate-loaded quatsomes for efficient localized therapy of recurrent aphthous ulcers. Quatsomes were prepared using a varied concentration of quaternary ammonium surfactants (QAS) and cholesterol (CHO). A 2 3 factorial design was conducted to address the impact of independent variables QAS type (X 1 ), QAS to CHO molar ratio (X 2 ), and sonication time (X 3 ). The dependent variables were particle size (PS; Y 1 ), polydispersity index (PDI; Y 2 ), zeta potential (ZP; Y 3 ), entrapment efficiency percent (EE%; Y 4 ) and percent of drug released after 6 h (Q6%: Y 5 ). Then, the selected quatsomes formula was incorporated into different gel bases to prepare an optimized mucoadhesive gel to be evaluated via in vivo study. The PS of the developed quatsomes ranged from 69.47 ± 0.41 to 113.28 ± 0.79 nm, the PDI from 0.207 ± 0.004 to 0.328 ± 0.004, ZP from 45.15 ± 0.19 to 68.1 ± 0.54 mV, EE% from 79.62 ± 1.44 to 98.60% ± 1.22 and Q6% from 58.39 ± 1.75 to 94.42% ± 2.15. The quatsomal mucoadhesive gel showed rapid recovery of ulcers, which was confirmed by the histological study and the evaluation of inflammatory biomarkers. These results assured the capability of the developed quatsomal mucoadhesive gel to be a promising formulation for treating buccal diseases.

The current study aims to develop niosomal nanocarriers for intranasal delivery of dronedarone hydrochloride to ameliorate its limited bioavailability. Niosomes were prepared by ethanol injection method and optimized using 3² full factorial experimental design. Both Span ® type (X1) and Span ® : cholesterol ratio (X2) were set as independent variables. Vesicle size (Y1), polydispersity index (Y2), zeta potential (Y3), and entrapment efficiency (Y4) were set as responses. The optimal formula was further incorporated into an ion-sensitive in situ gelling polymer for intranasal delivery. Optimal formula (N7), which is composed of Span ® 80: cholesterol (1:1), was of the least vesicle size (121.27 ± 13.31 nm), least polydispersity index (0.43 ± 0.073), highest zeta potential (-22.23 ± 2.84 mV) and highest entrapment efficiency (73.44 ± 2.8%). About 75.86% and 60.29% of dronedarone hydrochloride were released from N7 dispersion and in situ gel, respectively, within 12 h, compared to only 13.3% released from a drug-free suspension. In vivo pharmacokinetic study on male New Zealand rabbits resulted in significantly higher C max , AUC 0-72, and AUC 0-∞ of intranasal niosomal in situ gel compared to oral suspension. Almost twofold amplification of relative bioavailability was obtained after intranasal administration of niosomal in situ gel (195.7%) compared to oral suspension.

This study aims to develop efficient topical therapy for keratomycosis using sertaconazolenitrate (STZN)-loaded leciplex (LP). The D-optimal design was used to optimize STZN-loaded LP by utilizing soy phosphatidylcholine (SPC) molar ratio (X 1 ), cationic surfactant molar ratio (X 2 ), and cationic surfactant type (X 3 ) as the independent variables, whereas their impact was studied for entrapment efficiency percent (EE; Y 1 ), particle size (PS; Y 2 ), polydispersity index (PDI; Y 3 ), zeta potential (ZP; Y 4 ), and permeability coefficient (Kp; Y 5 ). The optimized formula was evaluated regarding morphology, ex vivo permeation, mucoadhesion, stability, and in vivo studies. The optimized formula was spherical and showed EE of 84.87 ± 1.71%, PS of 39.70 ± 1.35 nm, PDI of 0.242 ± 0.006, ZP of +54.60 ± 0.24 mV, and Kp of 0.0577 ± 0.0001 cm/h. The ex vivo permeation study revealed that the optimized formula enhanced the Kp and corneal deposition by 2.78 and 12.49 folds, respectively, compared to the aqueous drug dispersion. Furthermore, the optimized formula was stable and revealed promising mucoadhesion properties. Finally, the in vivo studies showed that the optimized formula was superior to the drug dispersion in treating rats with induced keratomycosis. These results confirmed the capabilities of LP as a promising nanocarrier for treating ocular diseases topically.

Bisoprolol hemifumarate (BH) is an antihypertensive drug that is used as first-line treatment for chronic hypertension and angina pectoris. Our study was performed to enhance the transdermal delivery of BH, a hydrophilic drug active with high molecular weight, through differently prepared hydrogels. The synergistic effect of permeation enhancers and iontophoresis was investigated via both ex vivo and in vivo permeation studies. Ex vivo iontophoretic permeation studies were performed by using male albino Wistar rat skin. Cellosolve ® hydrogel (F7) showed a 1.5-fold increase in Q 180 , Jss, and FER compared to F5 (lacking permeation enhancer). BH pharmacokinetic data were studied in human volunteers, following transdermal delivery of F7, using Phoresor ® Unit II iontophoresis device, compared to conventional oral tablets. F7 showed 1.9- and 2-fold higher values of C max and AUC 0-40 , respectively compared to Concor ® tablets, as well as a smaller T max (2.00 ± 2.00 h). The relative bioavailability of F7 was found to be 201.44%, relative to Concor ® tablets, demonstrating the significantly enhanced transdermal permeation of BH from the selected hydrogel by iontophoresis, in human volunteers. Finally, results showed the successful utility of permeation enhancers combined with iontophoresis in significantly enhanced transdermal permeation of BH, despite its large molecular weight and hydrophilic nature. Therefore, this strategy could be employed as a successful alternative route of administration to conventional oral tablets.

Acetazolamide (ACZ) is a diuretic used in glaucoma treatment; it has many side effects. Carvedilol (CAR) is a non-cardioselective beta-blocker used in the treatment of elevated intraocular pressure; it is subjected to the first-pass metabolism and causes fluids accumulation leading to edema. This study focuses on overcoming previous side effects by using a topical formula of a combination of the two previous drugs. Sixty formulations of niosomes containing Span 20, Span 60, Tween 20, and Tween 60 with two different ratios were prepared and characterized. Formulation with the lowest particle size (416.30 ± 0.23), the highest zeta potential (72.04 ± 0.43 mv), and the highest apparent coefficient of corneal permeability (0.02 ± 0.29 cm/h) were selected. The selected formula was incorporated into the gel using factorial design 2 3 . Niosomes (acetazolamide/carvedilol) consisting of Span 60 and cholesterol in the molar ratio (7:6), HMPC, and carbopol with two different ratios were used. The selected formula was subjected to an in vivo study of intraocular pressure in ocular hypertensive rabbits for 60 h. The sustained gel formula of the combination decreased (IOP) to normal after 1 h and sustained efficacy for 4 days. Histological analysis of rabbit eyeballs treated with the selected formula showed improvement in glaucomatous eye retinal atrophy.

Biopolymeric chitosan structure (Cs) is rationally investigated owing to its potentiality in pharmaceutical applications. The synthetic routes of biomimetic Cs-based blend electrospun nanofibers were studied. Herein, biocompatible crosslinked electrospun polyvinyl alcohol (PVA)/Cs-reduced gold nanoparticles (Cs(Rg))/β-CD (beta-cyclodextrin) in pure water were fabricated. To this end, supportive PVA as a carrier, Cs bio modifier, and gold reductant and β-CD as smoother, inclusion guest molecule, and capping agent exhibit efficient entrapment of moxifloxacin (Mox) and consequently accelerate release. Besides, PVA/Cs(Rg)/β-CD paves towards controlled drug encapsulation-release affinity, antimicrobial, and for wound dressing. Without losing the nanofiber structure, the webs prolonged stability for particle size and release content up to 96.4%. The synergistic effect of the nanoformulation PVA/Cs(Rg)/β-CD against pathogenic bacteria, fungus, and yeast, including Staphylococcus aureus , Escherichia coli , Candida albicans , and Aspergillus niger , posed clear zones up to 53 φmm. Furthermore, a certain combination of PVA/Cs (Rg)/β-CD showed a total antioxidant capacity of 311.10 ± 2.86 mg AAE/g sample. In vitro cytotoxicity assay of HePG2 and MCF-7 NF6 can eradicate 34.8 and 29.3 µg/mL against selected cells.