Objectives: This study aimed to develop hesperidin solid lipid nanoparticles (HESP-SLNs) to enhance their stability, solubility, and sustained release for wound healing; further enhancement was achieved through prepared nanostructured lipid carriers (HESP-NLCs) using Tea Tree Oil (TTO) to explore their synergistic efficacy. Methods: A factorial design of 2⁴ trials was established to evaluate the influence of lipid type (X1), lipid conc (%) (X2), surfactant type (X3), and sonication amplitude (%) (X4) of prepared HESP-SLNs on the particle size (nm) (Y1), polydispersibility index (Y2), zeta potential (Y3), and encapsulation efficiency (%) (Y4). The optimized HESP-SLNs formula was selected utilizing Design Expert^® software version 13, which was additionally enhanced by preparing TTO-loaded HESP-NLCs. In vitro release, Raman spectroscopy, and transmission electron microscopy were carried out for both lipid nanoparticles. Cytotoxicity, in vivo wound-healing assessments, and skin irritancy tests were performed to evaluate the performance of TTO-incorporated HESP-NLCs compared to HESP-SLNs. Results: The optimized formula demonstrated PS (280 ± 1.35 nm), ZP (−39.4 ± 0.92 mV), PDI (0.239 ± 0.012), and EE% (88.2 ± 2.09%). NLCs enhanced Q6% release, (95.14%) vs. (79.69%), for SLNs and showed superior antimicrobial efficacy. Both lipid nanoparticles exhibited spherical morphology and compatibility between HESP and excipients. NLCs achieved the highest wound closure percentage, supported by histological analysis and inflammatory biomarker outcomes. Cytotoxicity evaluation showed 87% cell viability compared to untreated HSF cells, and the skin irritancy test confirmed the safety of NLCs. Conclusions: TTO-loaded HESP-NLCs are promising candidates exhibiting superior wound-healing capabilities, making them a potential therapeutic option for cutaneous wound management.

Purpose: Nano-forensics is the latest application of nano-based technology for the purpose of fingerprint detection to improve precision, expedite investigations, and enhance safety. Solid lipid nanoparticles (SLNs) represent a promising pharmaceutical nanocarrier system for different applications. This study focused on applying ZnO and/or curcumin nanoparticles (NPs) to SLNs for the purpose of fingerprint detection to improve their sensitivity, safety and selectivity. Methods: A factorial design was utilized to select the optimized Cur-SLNs and ZnO-SLNs on the basis of the smallest particle size (PS), the lowest polydispersity index (PDI) and the highest zeta potential (ZP) value. To select the safe SLN-NPs, a cytotoxicity test was applied and they were compared to the most commonly applied product in fingerprint detection. The optimized formula was investigated according to the morphological structure; confocal spectroscopy and a stability study at different storage conditions were applied. Then the SLN-NPs were evaluated for their sensitivity, efficacy and selectivity in fingerprint detection. Results: The obtained optimal Cur-SLNs and ZnO-SLNs showed a nano PS of 221.55 ± 1.34 nm and 313.950 ± 1.87 nm, respectively, a PDI value < 0.7 and a ZP > 20 mV. The cytotoxicity data demonstrate that Cur-SLNs have low toxicity, so they will be the chosen formula. TEM and Raman spectroscopy analysis of the optimized Cur-SLN formulation validated the encapsulation efficiency and structural integrity of the pharmaceutical nanosystem. Furthermore, the powder showed stability and good results with higher adherence but smudged the prints on surfaces due to the slightest moisture. Conclusions: Overall, the results confirmed that Cur-SLN nanopowders can be developed as a suggested alternative to the current toxic powders used for latent fingerprint detection in forensic science, but only after further research on various surfaces and in different conditions.

Objective: Vortioxetine HBr is a multimodal antidepressant with a very poor aqueous solubility (50 µg base/ml at pH 7.4) and an oral bioavailability of approximately 75% due to hepatic first-pass metabolism. Nose-to-brain drug delivery can bypass hepatic first-pass metabolism and achieve targeted drug therapy by circumventing the blood-brain barrier via the olfactory and trigeminal nerve pathways using different modalities. A novel dosage form, nasal insert, containing Vortioxetine HBr lipid-based nanocarriers (VRT-NLCs) was used to improve Vortioxetine bioavailability and optimization of different additives such as D-(+)-Trehalose and D-Mannitol to enhance Vortioxetine efficacy. Methods: (VRT-NLCs) were prepared via a 24 full factorial design with four variables; surfactant (Tween 80) concentration (X1), steric stabilizer (PVA) concentration (X2), solid/liquid (Stearic/Oleic acid) ratio (X3), and co-surfactants (Span 60/Poloxamer 188) ratio (X4). Entrapment efficiency (EE%), %released after six hours (Q6h%), particle size (PS), zeta potential (ZP) and polydispersity index (PDI) were evaluated. Design Expert® software was used to select the optimum two formulae with the highest desirability values. Using D-mannitol or D-(+)-trehalose, the two optimized (VRT-NLCs) formulae were incorporated into lyophilized nasal inserts. They were characterized for physical appearance, release profile, muco-adhesion strength, residual water content by Karl Fischer, uniformity of dosage units by content uniformity, mass uniformity and friability. In addition to (DSC), (FTIR), (PXRD) and in vivo pharmacokinetics, the two optimized inserts were evaluated for (Norepinephrine (NE), Dopamine (DA), Serotonin (5-HT), Aspartate (Asp) and γ-amino butyric acid (GABA)) neurotransmitters’ level in the brain and (5-Hydroxy Indoleacetic acid (5HIAA)) metabolite using rats and compared with Vortoxicalm® 5 mg oral tablet. Results: (VRT-NLCs) exhibited (EE%) range of (67.58±1.59% to 99.42±1.91%), sustained release profile with (Q6h%) of (21.49±4.89% to 90.94±4.02%), (ZP)of (-10.4775±0.81to-27.925±2.67mV), (PS) of (81.92±0.68 to 255±5.82 nm), and (PDI)of (0.267±0.02 to 0.545±0.01). Moreover, nasal inserts had promising residual water content values of (0.0072 ±0.03% to 3.971±1.334 %), friability of (zero% to 0.9%), (Q)45 min% of (54.88 ±1.62% to 100 ±3.31%) and muco-adhesion strength of (8297.33±184.79 to 9996±122.23). Solid-state characterization (DSC and PXRD) confirmed D-(+)-trehalose superior cryoprotective effects. N4 (trehalose-based insert) demonstrated the highest brain exposure, with two-fold higher area under the curve from zero to infinity (AUC₀–∞ = 461.28±17.85ng*h/g) when compared to oral tablet (AUC₀–∞ = 230.4±11.5ng*h/g). Nasal inserts increased mood-regulating neurotransmitters’ (5-HT, DA, NE) levels and reduced (5-HIAA) metabolite compared with Vortoxicalm® 5 mg FCT. Conclusion: We recommend conducting further clinical studies to explore potential therapeutic applications of vortioxetine HBr lipid-based nanocarriers, consolidating our research findings.