الفهرس 
- Introduction and Literature SurveyOnly 14 pages are availabe for public view
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Abstract
Over the past few decades, fungal strains that trigger infections have consistently been considered as a pharmaceutical challenge. Aside from the crucial role that selenium and zinc ions play in biological systems, Selenium and zinc-based medications and imaging agents are frequently utilized in medicine for both the detection and treatment of a wide range of illnesses. The use of selenium and zinc ions in the form of mixed ligand complexes offers a unique advantage as antifungal agents. The topical treatment of numerous aesthetic and dermatological disorders, such as dandruff, acne, keratosis, age spots, and irregular keratinization, which was proven to be successful when using α- hydroxy acids (AHA), β-hydroxy acid (BHA), and related substances. The commonly utilized classes of these hydroxy acids are the α-hydroxy acids (e.g. glycolic acid) and β-hydroxy acids (e.g. salicylic acid). The goal of our research is to prepare complexes that enable the usage of hydroxyl and amino acids in their bioavailable forms. Se (II) and Zn (II) mixed ligand complexes containing glycine (gly) and pyroglutamic acid (L-PCA) as primary ligands and salicylic acid (HL1) and glycolic acid (HL2) as secondary ligands utilizing Se(II) and Zn(II) are perfect candidates because at physiological pH 7.4. They can generate selenium hydroxide or zinc hydroxide, respectively, which enables the formation of functional complexes of amino acids and hydroxyl acids.
Nanostructured lipid carriers (NLCs) are considered novel delivery systems and are also known as second-generation lipid nanocarriers that have been developed to substitute first- generation lipid nanoparticles.
On reacting Selenium (Se (II)) and Zinc (Zn (II)) mixed ligand complexes containing glycine (gly) and pyroglutamic acid (L-PCA) as primary ligands, and salicylic acid (HL1) and glycolic acid (HL2) as secondary ligands the complexes obtained have the following structure [Se (L1) (Gly)], [Se (L2) (Gly)], [Zn (L1)( L-PCA)] and [Zn (L2)(L-PCA)].
Result and discussion
• The elemental analysis revealed the formation of [1:1:1], matching the generic formula ”Se (II) /Zn (II) Amino Acid Hydroxy Acid”. The four complexes’ elemental composition and molecular weights confirm the absence of water molecules during crystallization.
• The IR spectra of the novel complexes were examined and compared to those of the free ligand. The distinctive v(C = O) carboxylate absorption band for HL1 and HL2 has been shifted to lower frequency for the complexes and emerged at 1590 cm-1, 1601 cm-1, 1592cm-1 and 1605 cm-1 for [Se (L1)(Gly)], [Se (L2)(Gly)], [Zn (L1)( L-PCA)] and [Zn (L2)( L-PCA)] complexes, respectively. The free ligands’ v(N-H) stretching vibration band (Glycine and L-PCA) appeared as a broad band at 3300 cm-1, 3365 cm-1, 3368 cm-1 and 3355 cm-1 for [Se (L1)(Gly)], [Se (L2)(Gly)], [Zn (L1)( L-PCA)] and [Zn (L2)( L-PCA)] complexes, respectively, due to
selenium and zinc’s coordination with the ligands’ OH and nitrogen without loss of proton (HL1 and HL2). This suggests that the nitrogen atoms have a role in the coordination of the ligands.
Selenium and zinc ions coordinate via the carboxylate group’s oxygen atom. The new symmetric v(M-O) vibration band emerges at 530 cm-1, 560 cm-1, 505 cm-1 and 510 cm-1 for Se [(L1)(Gly)], [Se (L2)(Gly)], [Zn (L1)( L-PCA)] and [Zn (L2)( L-PCA)] complexes,
respectively.
Selenium and zinc ions coordination with the nitrogen atom also displays bands at 592 cm-1, 601 cm-1, 560cm-1and 570 cm-1 for [Se (L1)(Gly)], [Se (L2)(Gly)], [Zn (L1)( L-PCA)] and [Zn (L2)( L-PCA)]
complexes, respectively.
The infrared data demonstrate the bidentate nature of hydroxy acids (HL1 and HL2) and amino acids with selenium and zinc ions via the carboxylate oxygen, hydroxyl group, and amino group.
• The molecular ion peaks of the complexes were studied to confirm their proposed molecular formulae. The multiple peak fragmentation patterns of the mass spectra elucidate the successive degradation of the complexes via the series of peaks assigned to the various fragments.
• The electronic spectra of the ligands are quite different from those of the complexes. The spectra feature bands at 305 nm and 370 nm for salicylic acid and bands at 251 nm and 300 nm for glycolic acid, due to aromatic ring intra-ligand transitions π→π* and n→π*. However, in the spectra of the complexes, slight shifts are observed in the position and intensity of these bands
compared to those of the ligands, which might be due to the coordination of metal with the ligand. An additional absorption band (above 400 nm) is observed in the electronic spectra of the complexes. which suggests the square planar geometry around the Se and Zn centers.
• Thermal stability of the synthesized mixed ligand complexes was investigated. The mixed ligand complexes underwent multiple stages of decomposition before transforming into their respective oxides at elevated temperatures.
• The H1NMR spectrum shows the disappearance of the peaks of δ HOH and δ HCOOH in the zinc complexes indicating the involvement of the oxygen atom of these groups in the complexation. A shift in the values of the protons of complexes in comparison to the protons and aromatic ring protons of the ligands also suggests complexation. Moreover, the shift in the peak of the NH protons in the complexes indicates bonding through the N atom of the NH group.
• All the complexes show sharp peaks indicating that the above complexes are crystalline in nature. The XRD patterns of the complexes are quite similar and suggest that the complexes have similar structures.
• The NLCs were prepared by a hot homogenization method. The formulations have particle sizes that vary from 215 to 245 nm and a PDI score of 0.3. The entrapment efficiency was found to be within the range of 75% to 80%. This highly satisfactory percentage of encapsulation confirms that NLC is a suitable
nanocarrier for the incorporation of mixed ligand complexes, which is expected since NLCs are one of the main systems for the incorporation of lipophilic drugs. The zeta potential of the prepared NLCs are negatively charged which indicates the absence of higher-level agglomeration within the system and the stability of NLCs. The microbiological activity of climbazole-mixed ligand complexes and their encapsulated forms were assessed against Malassezia furfur, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans and Escherichia coli. In comparison to Se (II) and Zn (II) mixed ligand complexes alone, the study revealed that the combination of Se (II) and Zn (II) mixed ligand complexes with climbazole in NLCs considerably increased antibacterial activity against the tested microbial strains. P ≤ 0.05 indicates statistical significance for the difference.
• Clinical Study
The anti-dandruff efficacy and tolerability of the produced mixed ligand complexes were evaluated using the weight and surface of the dandruff scales.To evaluate the efficacy of the treatment regimen aimed at preventing dandruff, 20 Egyptian volunteers with pre-existing dandruff conditions adhered to the prescribed instructions over a duration of 6 weeks. The clinical and instrumental evaluations conducted at the study’s commencement, as well as at the 4-week and 6-week intervals during the 6-week treatment period, yielded the subsequent findings. For Zn (L1)( L-PCA)]/climbazole NLC, there is statistically significant decrease in the weight of the dandruff scales ( T6 -
64.13%) and in the surface of the dandruff flakes on the L* parameter, D-Squame values (T6 -24.79%). Also, there is statistically significant decrease in the weight of the dandruff flakes (T6 -49.47%) and in the surface of the dandruff flakes on the L* parameter, D-Squame values (T6 -13.49%) for [Se (L1)(Gly)]. Likewise, the observed results for [Zn (L1)( L-PCA)] showed a statistically significant decrease in the weight of the dandruff scales ( T6 -51.06%) and in the surface of the dandruff flakes on the L* parameter, D-Squame values (T6 -12.66%). The obtained results demonstrate that the combination of Zn(II) and Se(II) mixed ligand complexes with azole compound incorporated in NLCs is more effective than unencapsulated mixed ligand complexes.