Pharmaceutical Nanotechnology - Volume 10, Issue 3, 2022

Background: Nucleic acid-mediated therapy holds immense potential in treating recalcitrant human diseases such as cancer. This is underscored by advances in understanding the mechanisms of gene regulation. In particular, the endogenous protective mechanism of gene silencing known as RNA interference (RNAi) has been extensively exploited. Methods: We review the developments from 2011 to 2021 using nano-graphene oxide, carbon nanotubes, fullerenes, carbon nanohorns, carbon nanodots and nanodiamonds for the delivery of therapeutic small RNA molecules. Results: Appropriately designed effector molecules such as small interfering RNA (siRNA) can, in theory, silence the expression of any disease-causing gene. Alternatively, siRNA can be generated in vivo by introducing plasmid-based short hairpin RNA (shRNA) expression vectors. Other small RNAs, such as micro RNA (miRNA), also function in post-transcriptional gene regulation and are aberrantly expressed under disease conditions. The miRNA-based therapy involves either restoration of miRNA function through the introduction of miRNA mimics; or the inhibition of miRNA function by delivering anti-miRNA oligomers. However, the large size, hydrophilicity, negative charge and nuclease-sensitivity of nucleic acids necessitate an appropriate carrier for their introduction as medicine into cells. Conclusion: While numerous organic and inorganic materials have been investigated for this purpose, the perfect carrier agent remains elusive. Carbon-based nanomaterials have received widespread attention in biotechnology recently due to their tunable surface characteristics and mechanical, electrical, optical and chemical properties.

Background: Epilepsy is one of the major neurological disorders, affecting about 50 million people globally. Oral, intravenous and rectal delivery systems are available for the management of epileptic seizures. However, intranasal delivery serves as beneficial for delivering antiepileptic drugs owing to the advantages it offers. Objective: Various approaches have been developed over the years aiming to attain either a safer or faster brain delivery; a nasal delivery system proposes significant outcomes. The noninvasiveness and high vascularity contribute to the high permeability of the nasal mucosa, allowing rapid drug absorption. This review highlights some promising novel approaches to efficiently deliver anti-epileptic drugs by employing the nasal route. Methods: The method includes a collection of data from different search engines like PubMed, ScienceDirect and SciFinder for obtaining appropriate and relevant literature regarding epilepsy, intranasal delivery of anti-epileptic agents, and novel therapeutics. Results: The present review underlines the majority of work related to intranasal delivery in the treatment of epilepsy, aiming to draw the attention of the researchers towards the easiest and most efficient ways of formulation for the delivery of anti-epileptics during seizures. Conclusion: This review intends to provide an understanding of the delivery aspects of antiepileptic drugs, the benefits of intranasal delivery and the novel approaches employed for the treatment of epilepsy.

Microbubbles are a new kind of delivery system that may be used to treat a variety of illnesses, including cancer. Microbubble is a non-invasive technology that uses microscopic gasfilled colloidal particle bubbles with a size range of less than 100 micrometres. This unique carrier has been used in a variety of applications in the last decade, ranging from basic targeting to ultrasound- mediated drug delivery. The oxygen in the microbubble lasts longer in the water. The drug release mechanism is highly regulated, since it releases the medication only in the appropriate areas, increasing the local impact while reducing drug toxicity. This carrier is exceptional in cancer medication delivery because of its sustained stability, encapsulation efficiency, and drug targeting. In this paper, we provide a comprehensive analysis of microbubble technology, including its manufacturing techniques and use in cancer medication delivery.

Background: β-artemether (BAT) and lumefantrine (LFT) combination therapies are well recognized for the treatment of malaria. However, the current conventional formulations have several drawbacks. Objective: The study aims to develop novel lipid nanoparticles (LNP) for efficient delivery of BAT and LFT. Methods: The LNP were prepared by solvent injection method and optimized by the Box-Behnken experimental design to achieve the desired particle size, maximum entrapment efficiency (EE), and percentage drug release. BAT and LFT in rat plasma were estimated by liquid chromatographytandem mass spectrometry (LC-MS/MS). Results: Freeze-dried LNP comprised of 78.74% (w/w) lipid, 15.74% (w/w) surfactant, 3.93% (w/w) co-surfactant and 1.57% mannitol with respect to the total inactive components. Mean particle size and zeta potential were found to be 140.22 ± 1.36 nm and -35.23 mv, respectively. EE was 80.60 ± 3.85% for BAT and 69.64 ± 2.63% for LFT. The optimized formulation exhibited a biphasic release profile in phosphate buffer (pH 7.2). In vivo study revealed an increased bioavailability of BAT and LFT from dual drug loaded LNP compared to the pure drug solution. Moreover, the tissue distribution study confirmed the high uptake of both the drugs in the liver and spleen. Conclusion: The study demonstrated the potential use of the developed formulation for oral administration in the treatment of malaria.

Background: Nanostructured lipid carriers (NLCs) are interesting lipid-based carrier systems for enhancing the penetration of drugs through the skin after topical administration. Objective: Dual drug-loaded NLCs of alpha-mangostin (M) and resveratrol (R) to enhance antioxidant activity were developed for topical delivery. Methods: The efficacy of a combination of M and R was evaluated in terms of the antioxidant activity. M and R were loaded into the NLCs using a high shear homogenization and ultrasonication process. The particle size, zeta potential, and physical properties of the NLCs were observed. The M and R loading efficiency, as well as release patterns, were examined using Franz diffusion cells. Moreover, the antioxidant efficacy and in vitro cytotoxicity in the normal human fibroblast (NHF) of the NLCs were evaluated as well. Results: The results found that the combination of M and R offered synergistic antioxidant activity and was successfully loaded into the NLCs with the size of a nanometer and negative zeta potential. The drugs were loaded in the NLCs as molecular dispersions and slowly released from the NLCs. Interestingly, both drugs maintained their antioxidant activity after being loaded into the NLCs and provided a higher antioxidant activity than those in the single loading of M and R, thus demonstrating that the incorporation of M and R into the NLCs allowed an enhanced antioxidant activity. Moreover, a cytotoxicity study showed that the NLCs were safe and had low cytotoxicity on the NHF cells. Conclusion: The M and R loaded NLCs were attractive systems for the synergistic antioxidant activity for topical application.

Background: Topical 5-fluorouracil (5FU) is one of the most prescribed medications for different types of skin cancer; however, it is associated with drug resistance and adverse effects. Rosemary extract has promising dose-dependent antitumor effects, as well as a synergistic effect in combination with 5-fluorouracil, besides sensitization of the 5-FU-resistant cells. Objective: Polymeric nanofibers loaded with 5FU and rosemary extract were optimized to combine both ingredients in one controlled release drug delivery system, aiming to enhance the efficacy while retaining the adverse effects. Methods: Polymeric nanofibers loaded with 5-FU and rosemary were fabricated via electrospinning technique. Design expert software was utilized to study the effect of independent variables, including polymer concentration, voltage, and feeding rate on the characteristics of the resulting nanofibers. Afterwards, the FTIR spectrum and release kinetic of the drug and extract from the optimized nanofibers and their cytotoxic effect against A375 cell line were investigated. Results: The formulation composed of 6.65% PVA electrospun at 1 mL.h^-1 and 17.5kV was chosen as the optimum fabrication condition. The mean diameter of the optimized nanofibers was 755 nm. The drug and rosemary extract contents were 75.38 and 93.42%, respectively. The fabrication yield was 100%, bioadhesion force was 1.28 N, and bead abundance was 10 per field. The cytotoxicity of the optimized formulation was significantly higher than the control groups. Conclusion: According to the appropriate loading percentage, release efficiency and release kinetics, bioadhesion force, and cytotoxicity, these nanofibers could be further investigated as a topical treatment option to increase the efficacy of 5-FU.