Pharmaceutical Nanotechnology - Volume 12, Issue 2, 2024

Botulinum neurotoxin has remarkably transitioned from a food safety hazard and biological warfare to an effective therapeutic drug. Currently, botulinum neurotoxins have seven serotypes (BoNT/A-G) in the form of protein complexes produced by Clostridium, a gram-positive and sporeforming bacteria. The conversion of toxins into useful drug substances of choice using the biotechnological process is tremendously increasing. Recent studies have shown that Botulinum neurotoxin-A (BoNT/A) has different biological activities and potencies in experimental and clinical conditions. They also indicate that the manufacturing process influences the potency and efficacy of BoNT/A drugs. Thus, this review focuses on the following criteria: detailed Fed-batch operation that includes the upstream and downstream processing of BoNT/A, the underlying mechanism behind the neurotoxic effect, and commercially available FDA-approved BoNT/A products and their therapeutic uses. Still, some research gaps exist in the mechanism for the treatment of psychiatric disorders.

Niosomes are lipid-based nanovesicles that have the potential to act as drug-delivery vehicles for a variety of agents. They are effective drug delivery systems for both ASOs and AAV vectors, with advantages such as improved stability, bioavailability, and targeted administration. In the context of brain-targeted drug delivery, niosomes have been investigated as a drug delivery system for brain targeting, but more research is needed to optimize their formulation to improve their stability and release profile and address the challenges of scale-up and commercialization. Despite these challenges, several applications of niosomes have demonstrated the potential of novel nanocarriers for targeted drug delivery to the brain. This review briefly overviews the current use of niosomes in treating brain disorders and diseases.

Background: Drug distribution to the eye is still tricky because of the eye’s intricate structure. Systemic delivery, as opposed to more traditional methods like eye drops and ointments, is more effective but higher doses can be harmful. Objective: The use of solid lipid nanoparticles (SLNPs) as a method of drug delivery has been the subject of research since the 1990s. Since SLNPs are derived from naturally occurring lipids, they pose no health risks to the user. To raise the eye's absorption of hydrophilic and lipophilic drugs, SLNs can promote corneal absorption and improve the ocular bioavailability of SLNPs. Methods: To address problems related to ocular drug delivery, many forms of nano formulation were developed. Some of the methods developed are, emulsification and ultra-sonication, high-speed stirring and ultra-sonication, thin layer hydration, adapted melt-emulsification, and ultrasonication techniques, hot o/w micro-emulsion techniques, etc. Results: Nanostructured lipid carriers are described in this review in terms of their ocular penetration mechanism, structural characteristic, manufacturing process, characterization, and advantages over other nanocarriers. Conclusion: Recent developments in ocular formulations with nanostructured bases, such as surfacemodified attempts have been made to increase ocular bioavailability in both the anterior and posterior chambers by incorporating cationic chemicals into a wide variety of polymeric systems.

Background: The goal of this work was to synthesize and fabricate matrix type transdermal patches based on a combination of polymers (Eudragit L100, HPMC and PVP K30), plasticizer and crosslinking agents (propylene glycol and triethyl citrate) and adhesives (Dura Tak 87-6908) to increase Thiocolchicoside (THC) absorption via topical route. This method allows avoidance of first-pass metabolism along with a consistent and extended duration of therapeutic activity. Methods: Fabrication and casting of polymeric solutions containing THC was done either in petri plates or through lab coater to get transdermal patches. Finally, the formulated patches were studied for their physicochemical and biological evaluation using scanning electron microscopy, FTIR, DSC, XRD and ex-vivo permeation studies using pig ear skin. Results: FTIR studies confirm that the THC characteristics peaks (carbonyl (Amide I) at 1525.5 cm^-1, C=O stretching (tropane ring) at 1664.4 cm^-1, Amide II band (N-H stretching) at 3325.9 cm^-1, thioether band at 2360.7 cm^-1, and OH group stretching band at 3400.2 cm^-1) are still present in the polymer mixture even after formulation as a transdermal patch, indicating compatibility among all excipients. While on the other hand, DSC studies confirm endothermic peaks for all the polymers along with THC with the highest enthalpy of 65.979 J/g, which is an indicator of sharp endothermic peak at 198°C, leading to the melting of THC. The percentage drug content and percentage moisture uptake of all the formulation was found in the range of 96 ± 2.04 to 98.56 ± 1.34% and 4.13 ± 1.16 to 8.23 ± 0.90%, respectively. Drug release and release kinetics studies confirm that it is dependent on the composition of individual formulation. Conclusion: All these findings support the possibility of using suitable polymeric composition, as well as proper formulation and manufacturing circumstances, to create a one-of-a-kind technology platform for transdermal drug administration.

> Background: Single-bulb garlic extract (SBGE) contains more active compounds than regular garlic, but it is unstable and easily degraded in the digestive tract. SBGE is expected to be protected by microencapsulation chitosan-alginate (MCA). Objective: The present study aimed to characterize and assess the antioxidant activity, hemocompatibility, and toxicity of MCA-SBGE in 3T3-L1 cells. Methods: The research procedures consist of extraction of single bulb garlic, preparation of MCASBGE, Particle Size Analyzer (PSA), FTIR analysis, DPPH assay, hemocompatibility test, and MTT assay. Results: The average size of MCA-SGBE was 423.7 ± 2.8 nm, the polydispersity index (PdI) was 0.446 ± 0.022, and the zeta potential was -24.5 ± 0.4 mV. MCA-SGBE was spherical with a diameter range of 0.65-0.9 μm. A shift in absorption and addition of functional groups was found in SBGE after encapsulation. MCA-SBGE, at a concentration of 24 x 10³ ppm, has higher antioxidants than SBGE. The hemocompatibility test shows the hemolysis of MCA-SBGE lower than SBGE. MCA-SBGE was not toxic to 3T3-L1 cells with cell viability percentage above 100% at all concentrations. Conclusion: MCA-SBGE characterization has microparticle criteria with homogeneous PdI values, low particle stability, and spherical morphology. The results showed that SBGE and MCA-SBGE are nonhemolytic, compatible with red blood cells, and non-toxic to 3T3-L1 cells.

>Introduction: Hydroxyapatite is a significant material that finds its application in the field of dental and bone tissue engineering. Methods: The formulation of nanohydroxyapatite with the aid of bioactive compounds has gained importance in recent years due to the beneficial activity contributed by them. The present work focuses on the formulation of nanohydroxyapatite synthesis using epigallocatechin gallate, an active biochemical component of green tea. Results: The prepared epigallocatechin gallate-mediated nanohydroxyapatite (epi-HAp) was nanoglobular in shape and composed of calcium, phosphorous, carbon and oxygen, which was confirmed by Scanning electron microscope- energy dispersive X-ray analysis (SEM-EDX). The Attenuated Total Reflection- Infra red spectroscopy (ATR-IR) and X-ray photoelectron spectroscopy (XPS) assured that the reduction and stabilisation of nanohydroxyapatite were mediated by epigallocatechin gallate. Conclusion: The epi-HAp exhibited anti-inflammatory behaviour along with nil effect on cytotoxicity. To be precise, the epi-HAp can be an effective biomaterial in bone and dental applications.

Background: In this study, a prototype of a targeted nanocarrier for drug delivery for prenatal therapy of the developing fetus was developed and examined in vitro and ex vivo. The folate transport mechanism in the human placenta was utilized as a possible pathway for the transplacental delivery of targeted nanoparticles. Methods: Several types of folic acid-decorated polymeric nanoparticles were synthesized and characterized. During transport studies of targeted and non-targeted fluorescent nanoparticles across the placental barrier, the apparent permeability values, uptake, transfer indices, and distribution in placental tissue were determined. Results: The nanoparticles had no effect on BeWo b30 cell viability. In vitro, studies showed significantly higher apparent permeability of the targeted nanoparticles across the cell monolayers as compared to the nontargeted nanoparticles (Pe = 5.92 ± 1.44 ×10^-6 cm/s for PLGA-PEG-FA vs. 1.26 ± 0.31 ×10^-6 cm/s for PLGA-PEG, P < 0.05), and the transport of the targeted nanoparticles was significantly inhibited by excess folate. Ex vivo placental perfusion showed significantly greater accumulation of the targeted nanoparticles in the placental tissue (4.31 ± 0.91%/g for PLGA-PEG-FA vs. 2.07 ± 0.26%/g for PLGA-PEG). Conclusion: The data obtained suggested different mechanisms for the uptake and transplacental transfer of targeted versus nontargeted nanoparticles. This targeted nanoformulation may be a promising strategy for fetal drug therapy.