Insight into lipid-based nanoplatform-mediated drug and gene delivery in neuro-oncology and their clinical prospects.

Tumors of the Central nervous System (CNS) are a spectrum of neoplasms that range from benign lesions to highly malignant and aggressive lesions. Despite aggressive multimodal treatment approaches, the morbidity and mortality are high with dismal survival outcomes in these malignant tumors. Moreover, the non-specificity of conventional treatments substantiates the rationale for precise therapeutic strategies that selectively target infiltrating tumor cells within the brain, and minimize systemic and collateral damage. With the recent advancement of nanoplatforms for biomaterials applications, lipid-based nanoparticulate systems present an attractive and breakthrough impact on CNS tumor management. Lipid nanoparticles centered immunotherapeutic agents treating malignant CNS tumors could convene the clear need for precise treatment strategies. Immunotherapeutic agents can selectively induce specific immune responses by active or innate immune responses at the local site within the brain. In this review, we discuss the therapeutic applications of lipid-based nanoplatforms for CNS tumors with an emphasis on revolutionary approaches in brain targeting, imaging, and drug and gene delivery with immunotherapy. Lipid-based nanoparticle platforms represent one of the most promising colloidal carriers for chemotherapeutic, and immunotherapeutic drugs. Their current application in oncology especially in brain tumors has brought about a paradigm shift in cancer treatment by improving the antitumor activity of several agents that could be used to selectively target brain tumors. Subsequently, the lab-to-clinic transformation and challenges towards translational feasibility of lipid-based nanoplatforms for drug and gene/immunotherapy delivery in the context of CNS tumor management is addressed.

Development of Lipidic Nanoplatform for Intra-Oral Delivery of Chlorhexidine: Characterization, Biocompatibility, and Assessment of Depth of Penetration in Extracted Human Teeth.

Microorganisms are the major cause for the failure of root canal treatment, due to the penetration ability within the root anatomy. However, irrigation regimens have at times failed due to the biofilm mode of bacterial growth. Liposomes are vesicular structures of the phospholipids which might help in better penetration efficiency into dentinal tubules and in increasing the antibacterial efficacy. Methods: In the present work, chlorhexidine liposomes were formulated. Liposomal chlorhexidine was characterized by size, zeta potential, and cryo-electron microscope (Cryo-EM). Twenty-one single-rooted premolars were extracted and irrigated with liposomal chlorhexidine and 2% chlorhexidine solution to evaluate the depth of penetration. In vitro cytotoxicity study was performed for liposomal chlorhexidine on the L929 mouse fibroblast cell line. Results: The average particle size of liposomes ranged from 48 ± 4.52 nm to 223 ± 3.63 nm with a polydispersity index value of <0.4. Cryo-EM microscopic images showed spherical vesicular structures. Depth of penetration of liposomal chlorhexidine was higher in the coronal, middle, and apical thirds of roots compared with plain chlorhexidine in human extracted teeth when observed under the confocal laser scanning microscope. The pure drug exhibited a cytotoxic concentration at which 50% of the cells are dead after a drug exposure (IC50) value of 12.32 ± 3.65 µg/mL and 29.04 ± 2.14 µg/mL (on L929 and 3T3 cells, respectively) and liposomal chlorhexidine exhibited an IC50 value of 37.9 ± 1.05 µg/mL and 85.24 ± 3.22 µg/mL (on L929 and 3T3 cells, respectively). Discussion: Antimicrobial analysis showed a decrease in colony counts of bacteria when treated with liposomal chlorhexidine compared with 2% chlorhexidine solution. Nano-liposomal novel chlorhexidine was less cytotoxic when treated on mouse fibroblast L929 cells and more effective as an antimicrobial agent along with higher penetration ability.