An Alternative Approach for Improved Entrapment Efficiency of Hydrophilic Drug Substance in PLGA Nanoparticles by Interfacial Polymer Deposition Following Solvent Displacement

Abstract

Background: Alzheimer's disease (AD) is an age-related and irreversible neurological disorder. The low efficacy of current therapeutic strategies is related to both poor drug potency and the presence of various obstacles in the delivery routes, such as blood-brain barrier (BBB) that limits the uptake of most drugs by the brain. Rivastigmine hydrogen tartrate (RHT) is used in mild to moderate forms of AD therapy. Objectives: The present study described the use of Poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs), as effective delivery vehicles, to improve the therapeutic efficiency of RHT. Methods: RHT-loaded PLGA NPs were prepared using interfacial polymer deposition, following solvent displacement method with different ratios of polymer: Drug. The NPs were studied for entrapment efficiency, particle size, and surface morphology, using scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). In vitro drug release from NPs was also assessed by a modified dissolution method. Results: The entrapment efficiency of RHT in NPs was found to be between 27.71 ± 6.86 and 45.70 ± 11.06 and the average size was about 75.14 to 173 nm. The zeta potential was negative (-2.28 to-10.5 mV), as determined by dynamic light scattering (DLS). The drug released from NP formulations was between 69.98% and 89% upon 24 hours, which indicated improved sustained drug release characteristics. Conclusions: These results suggested the potential usefulness of PLGA NPs for the delivery of RHT in a sustained and controlled manner.

Multifunctional Polymeric Nanoplatforms for Brain Diseases Diagnosis, Therapy and Theranostics

“…Biodegradable delivery systems based on the PLGA polymer have been used in the imaging, diagnostics, and treatment of diseases [184][185][186][187]. Entrapment of various types of drugs such as proteins, peptides, genes, and anticancer drugs has been performed in PLGA NPs [188][189][190][191]. Protein and peptide drugs are susceptible to high temperature or acidic environments.…”

Safety and Toxicity Issues of Therapeutically Used Nanoparticles from the Oral Route

“…The size of NPs is one of the most important parameters affecting their oral toxicity [47]. The large surface area to volume ratio of NPs aids their harmful interactions with the biological systems, modifying cellular uptake [48]. According to the previous studies, smaller particles may pass through the enterocyte cell membranes, causing membrane fluidity.…”

Formulation and Evaluation of Eudragit RL-100 Nanoparticles Loaded In-Situ Forming Gel for Intranasal Delivery of Rivastigmine

“…The RHT release from the plain drug gel and nanoformulations was studied using the dialysis bag diffusion technique. 22 To this end, the RHT nanoformulations (1 g, gel state) were placed in the dialysis bags containing nasal simulated fluid (NSF, 1 mL). Dialysis membranes were then immersed in vials filled with PBS (25 mL), placed in a shaker incubator and shaken at 100 rpm for 24 hours at 32 ± 1˚C.…”