Advancements in Neurodegenerative Therapy: Developing and Optimizing a Polymeric Nanoparticles-Loaded Gel for Nasal Delivery of Anti-Alzheimer Drugs
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ABSTRACT Background: Polyphenols, a class of naturally occurring compounds, are recognized for their diverse biological activities, with a notable focus on their anti-neurodegenerative properties. Curcumin and gallic acid, prominent polyphenols, have demonstrated effectiveness as anti-Alzheimer agents. Objective: The aim of this research is to develop a herbal gel for the nasal delivery of an anti-Alzheimer drug. The strategy involves formulating nanoparticles of curcumin and gallic acid using the coacervation technique to enhance solubility, permeability, and bioavailability via nasal administration. Method: A pH-dependent gel based on Carbopol 934 and Carbopol 940 was formulated, incorporating nanoparticles of curcumin and gallic acid. The formulated gel underwent thorough evaluation, including assessments for drug content, entrapment efficacy, XRD, FTIR, viscosity, particle size analysis, zeta potential, DSC, and polarized microscopy. Results: The developed formulation exhibited positive results in terms of drug content, entrapment efficacy, and various physicochemical characteristics. Stability studies over a three-month period were conducted to ensure the robustness and longevity of the optimized formulation. Conclusion: This research presents a significant advancement in the utilization of polyphenols, particularly curcumin and gallic acid, for the treatment of Alzheimer's disease. The nasal delivery system, incorporating nanoparticles in a herbal gel matrix, offers enhanced solubility and bioavailability, contributing to the potential efficacy of anti-Alzheimer drugs. The findings pave the way for further exploration and application of polyphenols in neurodegenerative disease therapeutics
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Materials and Methods: 1. Curcumin (Cur) and Gallic Acid (GA) Acquisition: Curcumin was obtained as a generous sample from Sigachi Industries Ltd. (Gujrat, India). Gallic Acid, Tween 80, and Ethyl acetate were sourced from Thermosil fine chem industries. Carbopol 934 and Carbopol 940 were acquired from chemdyes corporation. Chitosan was procured from a reputable research lab. All chemicals used were of analytical grade, ensuring reliability. 2. Preparation of Simulated Nasal Fluid (SNF): SNF was prepared by dissolving sodium chloride, potassium chloride, and calcium chloride in distilled water. The resulting solution's pH was adjusted and maintained at 6.5. 3. Preformulation Studies: 3.1 Determination of λ Max of Curcumin and Gallic Acid: Stock solutions of curcumin and gallic acid were prepared and analyzed using a UV-visible spectrophotometer to determine the absorption maximum wavelength. 3.2 Fourier Transfer Infrared Spectral Studies: Compatibility study using FTIR with samples prepared in a 1:1 w/w ratio of drugs and excipients. 3.3 Differential Scanning Calorimetry: DSC analysis on pure drug and formulated gel to assess thermal characteristics. 4. Preparation of Nanoparticles: Nanoparticles of Curcumin and Gallic Acid were formulated using the Coacervation (desolvation) technique. Ethyl acetate was used to dissolve drugs, added dropwise to a chitosan solution with Tween 80. The solution underwent centrifugation, and obtained nanoparticles were dried to yield powdered particles. Four batches with different drug-to-polymer (DP) ratios were prepared, with 1:1 DP ratio chosen for subsequent studies. 5. Characterization of Nanoparticles: 5.1 Surface Morphology: Surface morphology assessed using a polarized microscope on nanoparticles dispersed in distilled water. 5.2 Particle Size and Poly Dispersity Index (PDI): Determined using a Beckman Coulter Counter (Delsa tm Nano) after appropriate dilution. 5.3 X-ray Diffractometer (XRD): XRD patterns determined using an X-ray Diffractometer (Bruker Axs, D8 Advance). 5.4 Drug Loading: Drug loading assessed by extracting Curcumin and Gallic Acid with SNF and analyzed spectrophotometrically. Percentage drug loading calculated using the specified formula: % DL=(amount of drug added in NP's)/(amount of Drug added+amount of excipients added)×100.