Current Nanomedicine - Volume 10, Issue 1, 2020

Background: Nanomedicine shows a huge promise for incurable diseases. So far, more than 50 nanoparticles have been approved by FDA and around 80 nanoformulations are currently in clinical trials. Nanoparticles possess several advantages over traditional drugs, including higher biocompatibility and bioavailability. One of the challenges for their wide application is insufficient understanding of the molecular network related to internalization of particles and intracellular release of cargos. Objective: This article aims to review the interactions between nanoparticles, vesicle transportation and autophagy pathways. The underlying molecular machinery is also discussed. Methods: For each step of the vesicle trafficking and autophagy, details of signaling pathways are described for a better understanding of the interactions between delivery vehicles and biomolecules within the cell. Conclusion: The selection of cellular uptake route mainly depends on physical characteristics of nanoparticles. For nanoparticles modified with ligands, they undergo receptormediated endocytic pathway. Once residing within the cells, cargos are released after disruption of endosomes, a mechanism called ‘proton sponge effect’. Besides, internalized nanoparticles either can be exocytosized, or they initiate the autophagy response, affecting the intracellular distribution of drugs.

It has been well documented that microbes are able to create self-defense against conventional antibiotics. Such drug-resistant property of the microbes always inspired the researchers to develop an alternative strategy to control the growth of pathogenic microbes. Nanoparticles have received major importance because of their distinctive property over corresponding bulk material. For such unique property, from the recent past, research has been focused on the nanotechnology to uplift the biomedical sciences but hazardous byproducts of nanoparticle synthesis makes always retardation. In this review, we emphasized and elaborated the biosynthesis process of metal nanoparticles and how such particles can be considered for anti-microbial context.

HER2 positive breast cancer is an aggressive breast cancer followed by brain metastasis, which emerges at the later stage of breast cancer or after a few years of treatment. HER2+ breast cancer brain metastasis is a complex fatal disease with short survival and resistance to first-line drugs such as Trastuzumab, lapatinib, etc. The resistance can be due to the upregulation/downregulation of various proteins of downstream pathways mainly PI3K/AKT pathway and MAPK pathway. In addition, the Blood-brain Barrier (BBB) and Blood Tumor Barrier (BTB) also hinder the delivery to brain metastases. Thus controlling the altered proteins of the downstream pathway can be a targeted approach to control breast cancer and its brain metastasis. At the same time, targeted delivery to metastatic sites can give a synergistic effect in controlling brain metastasis and increasing the survival period. Various type of targeted nanocarriers such as single, dual, or multitargeted, pH specific, or stimuli sensitive nanocarriers can be employed for providing specific delivery to HER2+ cancer cells. Furthermore, combinations such as Trastuzumab with tyrosine kinase inhibitors (lapatinib, neratinib, afatinib), chemotherapeutic drugs (paclitaxel, doxorubicin, capecitabine), or some natural compounds (curcumin, Lycorine, berberine) with anti-apoptotic activity can provide an additional effect in the management of HER2 positive breast cancer and its metastasis.

Background/Objectives: Donepezil (DPL) is available as the hydrochloride salt (DPL-HCL) which is highly water-soluble, prompting leakage of the drug into water phase during solid lipid nanoparticles (SLNs) preparation which leads to reduce the entrapment efficiency as well as drug content. So, the drug was converted into its base form i.e. donepezil base (DPL base). The main objective of the work was to study the physicochemical characterization and identification of DPL base and to compare it with parent DPL-HCL, to develop a High-Performance Liquid Chromatography (HPLC) method for the detection of DPL base in SLNs. The develop method was used for the determination of shelf life of drug in SLNs. Methods: DPL-HCL was converted into DPL base simply by alkalization of DPL- HCL with NaOH and then extracted into dichloromethane (DCM) followed by drying to obtain DPL base. The HPLC method was developed and validated to quantify the DPL base for the determination of its shelf life in SLNs. The drug content in the developed SLNs was determined by extracting the DPL base using methanol as a solvent. The method was validated for linearity, precision, accuracy, reproducibility, limit of detection (LOD) and limit of quantification (LOQ). Results: DPL-HCL was successfully converted into DPL base with a yield value of 88.61%. The optimized mobile phase was comprised of 0.02 M phosphate buffer (pH 7.4), methanol and Acetonitrile (ACN) (40:50:10 v/v/v). The pH of mobile phase was adjusted with o-phosphoric acid. The linearity range of the developed method was found to be 0.5-80 μg/mL with LOD and LOQ value 0.086 and 0.263 μg/ml respectively. The shelf life of the DPL base in SLNs was found to be 2.29 years. Conclusion: The HPLC method for donepezil base was successfully developed and validated. RSD values for validated parameters were < 2, indicating the authenticity of the developed method. The method was successfully used for the determination of shelf life of the drug in SLNs.

Purpose: This study assesses the kinetics of the anti-tumor drug chlorambucil (CLB) incorporated into PLGA nanoparticles (NP-CLB) with and without the presence of the O-stearoyl mannose (OEM) functionalizing agent (NP-CLBMAN). Methods: OEM was synthesized and used in the NP-CLB-MAN formulation. The nanoparticles were characterized by dynamic light scattering, electrophoretic light scattering, scanning electron microscopy, and Fourier-transform infrared spectroscopy. Results: The nanoparticles presented an encapsulation efficiency greater than 61% and a PdI between 0.186–0.217. The mean size was 185 nm for NP-CLB and 220 nm for NPCLB- MAN, and the zeta potential values were -17.7 mV for NP-CLB and -14.2 mV for NP- CLB-MAN. Scanning electron microscopy showed that NPs with OEM have a surface with a different shape, and FTIR analyses showed binding of CLB to the drug delivery system, as well as functionalization with OEM. In vitro release studies showed a biphasic release profile for both systems, and they were analyzed considering the mathematical Korsmeyer-Peppas, first-order, and Fick diffusion models, and the combination of the first-order and Fick diffusion models. Conclusion: The experimental results obtained for the release of CLB were better described using a combination of the first order and Fick diffusion mathematical models.

Background: It has been hypothesized that delivery of aripiprazole through nanoemulsion formulation would better deliver the drug into the central nervous system to treat major depressive conditions in psychological patients. Due course of formulation development, to determine solubility of the drug in different matrices and nanoemulsion is an important step. Materials & Methods: Therefore, a simple, rapid and selective reversed phase high performance liquid chromatographic (RP-HPLC) method was developed and validated for the determination of aripiprazole as per International Conference of Harmonization (ICH) guidelines. Satisfactory analysis method was employed for the quantitative determination of aripiprazole during pre-formulation development. Results and Discussion: The separation technique was achieved using the mobile phases of methanol-acetonitrile, 80:20 (v/v) delivered at 1.0 mL.min-1 flow rate through HIQ SIL C18 250x4.6 mm (5 μm particle size) column and detected at 218 nm wavelength. The method depicted linear calibration plots within the range of 5 to 50 μg.mL-1 with a determination coefficient (r2) of 0.9991 calculated by least square regression method. The validated method was sensitive with LOD of 10.0 ng.mL-1 and 30.0 ng.mL-1 of LOQ. The intra-day and inter-day precision values were ranged between 0.37-0.89 and 0.63-1.11 respectively, with accuracy ranging from 98.24 to 100.88 and 97.03 to 100.88, respectively. This developed and validated method was found to be sensitive for the determination of aripiprazole for the first time from various oils, surfactants, co-surfactants, and nanoemulsion formulation. Conclusion: This RP-HPLC method was successfully implemented for the quantitative determination of aripiprazole at developmental stages of nanoemulsion formulation.