Formulation and Evaluation of PLGA Nanoparticulate-Based Microneedle System for Potential Treatment of Neurological Diseases

Abstract

The tight structure of the blood-brain barrier severely limits the level of drug therapy for central nervous system disorders. In this study, a novel composite delivery system combining nanocarrier and microneedle technology was prepared to explore the possibility of transdermal delivery of drugs to work in the brain. Methods: Nanoparticle solutions containing paroxetine and rhodamine-B were prepared using PLGA as a carrier by the emulsification-solvent volatilization method. Then, they were mixed with hyaluronic acid and the PLGA nanoparticulate-based microneedle system (Rh-NPs-DMNs) was prepared by a multi-step decompression-free diffusion method. The particle size, zeta potential, and micromorphology of the nano solution were measured; the appearance, mechanical strength, dissolution properties, and puncture effect of the Rh-NPs-DMNs were evaluated; also, it was evaluated for in vivo live imaging properties and in vitro skin layer transport and distribution properties. Results: The mean particle size of Rh-NPs was 96.25 ± 2.26 nm; zeta potential of 15.89 ± 1.97 mV; PDI of 0.120 ± 0.079. Rh-NPs-DMNs had a high needle content of 96.11 ± 1.27% and a tip height of 651.23 ± 1.28 μm, with excellent mechanical properties (fracture force of 299.78 ± 1.74 N). H&E skin tissue staining showed that Rh-NPs-DMNs produced micron-sized mechanical pores approximately 550 μm deep immediately after drug administration, allowing for efficient circulation of the drug; and the results of in vivo imaging showed that Rh-B NPs DMNs had a faster transport rate than Rh-B DMNs, with strong fluorescent signals in both brain (P<0.01) and hippocampus (P<0.05) 48 h after drug administration. Conclusion: Nanoparticles can prolong blood circulation time and intracerebral retention time and have certain brain-targeting properties due to their excellent physical properties. The use of microneedle technology combined with nanocarriers provides new ideas for delivery systems for the treatment of central neurological diseases.

Research Progress of Extracellular Vesicles-Loaded Microneedle Technology

“…While polymers and hydrogel materials demonstrate promising application prospects, current research often transcends the use of a single, simple polymer for MN fabrication [ 108 ]. Instead, researchers are exploring related modifications or combinations of various materials to achieve enhanced application outcomes [ 109 ]. For instance, the development of multifunctional MNs based on a magnesium metal–organic framework combined with hydrogel has shown significantly improved wound healing in diabetic mice [ 110 ].…”

Application of hydrogel microneedles in the oral cavity

“…Currently, PLGA is often processed into nanoparticles to carry drugs and mixed with other hydrogel materials to prepare microneedles by the micromolding technique. [115] PLGA is used to stabilize the internal components of microneedles for drug delivery and controlled release. [116] 3.4.…”

Key Transdermal Patch Using Cannabidiol-Loaded Nanocarriers with Better Pharmacokinetics in vivo

“…A transdermal drug delivery system (TDDS) utilizes the skin to administer therapeutic agents. 21,22 These agents permeate the skin, are absorbed into the blood vessels, and are distributed throughout the body. [23][24][25] TDDS offer noninvasiveness, minimal pain, first-pass metabolism bypassing, ease of administration, independence from medical personnel, and potential applicability to a wide range of hydrophilic and hydrophobic drugs.…”