Current Drug Delivery - Volume 20, Issue 2, 2023

Cancer is one of the most lethal diseases of the twenty-first century. Many medicines, including antitumor antibiotics, deliver tedious and severe chemotherapy and radiation treatment, both of which have significant side effects. DNA nanorobots, as an alternative, might be used as a cancer treatment method that is both safer and more precise than current treatments. DNA nanobots are being praised as a major milestone in medical research. The major goal of these nanobots is to find and destroy malignant cells in the human body. A unique strand of DNA is folded into the systematic form to create these nanobots. DNA origami has magnified passive tumor-targeting and prolonged properties at the tumor location. The triangle-like DNA origami, in particular, shows excellent accumulation on passive targeting of the tumor. Self-built DNA origami nanostructures were utilized to deliver the anticancer drug doxorubicin into tumors, and the approach was found to be highly successful in vivo. In another demonstration, a robot was made with the help of DNA origami and aptamer for folding a 90nm long tube-like apparatus. It was carried out to transport the blood coagulation protease thrombin in the interior portion guarded against blood plasma protein and circulating platelets. The robot unfolded once the aptamer was identified and attached to its tumor-specific target molecule, delivering thrombin to the circulation, stimulating coagulation of the regional malignant cells, and proceeding to tumor necrosis and tumor growth inhibition. Various studies revealed the effectiveness of DNA nanobots in cancer therapy.

Natural products contain bioactive compounds that are produced naturally via synthetic or semisynthetic processes. These bioactive compounds play significant biological roles, especially for growth as well as in defense mechanisms against pathogens. Bioactive compounds in natural products have been extensively studied in recent decades for their pharmacological activities, such as anticancer, wound healing, anti-microbial, anti-inflammatory, and anti-oxidative properties. However, their pharmaceutical significance has always been hindered by their low bioavailability and instability with variations in pH, temperature, and exposure to light. Nanotechnology paves the way for the development of drug delivery systems by enhancing therapeutic efficacy. Nanostructured lipid carriers, a lipidbased drug delivery system, are recently being studied to improve the biocompatibility, biodegradability, bioavailability, solubility, permeability, and shelf life of bioactive compounds in the pharmaceutical industry. The ideal component and preparation method for bioactive compounds in nanostructured lipid carrier development is necessary for their physicochemical properties and therapeutic efficiency. Therefore, this review seeks to highlight recent developments, preparation, and application of nanostructured lipid carriers as carriers for natural bioactive compounds in improving their therapeutic potential in drug delivery systems.

Migraine is a disabling disease characterized by severe throbbing headaches. Patients demand quick relief from this pain. The presence of the blood-brain barrier does not permit the drug to penetrate the brain effectively. Administration of conventional anti-migraine medications via oral route leads to erratic absorption of drugs. Delayed gastric emptying is also responsible for the ineffective absorption of the drug. Migraine-induced nausea and vomiting further limit patient compliance to oral medication. Other limitations associated with the oral route include extensive first-pass metabolism, slow onset of action, inability to cross the blood-brain barrier, requirement of a large amount of dose/dosage, and frequent administration. The anti-migraine drugs used in migraine, such as triptans, are therapeutically effective but have low bioavailability on oral administration. Also, these drugs are associated with several cardiovascular complications. The oral dose of most antimigraine drugs, oral triptans, Ergotamine, NSAIDs, and CGRP antagonists is quite high because of their poor bioavailability. As a result, these drugs are associated with several side effects. This aspect necessitates the need to develop a dosage form that can deliver drugs directly to the brain, thereby reducing the dose. Invasive techniques to deliver these therapeutics to the brain do exist. However, they are painful, require expert assistance, and are not a cost-effective approach for migraine treatment. These limitations demand the development of a novel non-invasive approach that is safe, efficacious, and has high patient compliance. According to reports, it is possible to target the brain tissue by administering the drug intranasally using the olfactory and the trigeminal pathway. This route is non-invasive, avoids first-pass metabolism, eliminates nausea and vomiting, helps reduce dose, and thus helps achieve increased patient compliance. Some factors like solubility, the lipophilicity of the drug, mucociliary clearance, and enzymatic degradation hinder the bioavailability of the drug by nasal route. Therefore, there is a grave need to develop novel nasal formulations with prolonged nasal residence time, which can modulate pharmacokinetics for adequate therapeutic response and render efficient yet robust brain targeting. Considering these challenges, developing an efficient intranasal dosage form is necessary. This review gives a brief overview of all the novel carriers reported for improving the treatment of migraine. Nanocarrier-based delivery systems like in situ gels, microemulsion, nanoemulsion, nanoparticles, vesicular systems, micelles, and microspheres used in nose to brain delivery of migraine therapeutics are also discussed in the article.

Background: Neuroinflammation resulting from oxidative and nitrosative stress is associated with various neurological disorders and involves the generation of pro-inflammatory cytokines and microglial activation. Dietary phytochemicals are safer and more valuable adjunct neurotherapeutic agents which can be added to the therapeutic regimen. These compounds provide neuroprotection by the modulation of various signaling pathways. Introduction: Naringenin (NGN) is a phytochemical having low oral bioavailability because of poor solubility, and adding to this limitation is enhanced efflux by P-glycoprotein transporters in neuroinflammatory diseases. Methods: Hence, as a solution for these limitations, naringenin encapsulated poly-lactic-co-glycolic acid (PLGA) nanocarriers were developed using the nanoprecipitation technique and coated with 1% glutathione (GSH) and 1% Tween 80 to enhance brain delivery. Results: Coated and uncoated NGN-PLGA nanoparticles (NGN-PLGA-NPs) were spherical, monodispersed, stable, and non-toxic, with a particle size of less than 200 nm. They had negative zeta-potential values, 80% entrapment efficiency, and sustained drug release of 81.8% (uncoated), 80.13%, and 78.43% (coated) in 24 hours. FT-IR, DSC, PXRD, and NMR confirmed the drug encapsulation and coating over nanoparticles. In vivo brain uptake showed greater fluorescence intensity of the coated nanoparticles in the brain than uncoated nanoparticles. In addition, there was a 2.33-fold increase in bioavailability after coating compared to naringenin suspension and enhanced brain uptake. Conclusion: Present studies indicate sustained and targeted brain delivery of naringenin via the ligandcoated delivery system by inhibiting enhanced P-glycoprotein (P-gp) efflux occurring in autism spectrum disorders due to neuroinflammation.

Objective: To improve the solubility of Honokiol (HNK), Honokiol nanoparticles (HNK-NPs) were prepared using a new biodegradable polysaccharide polymer as its carrier. Methods: HNK-NPs were prepared by hydrophilic polymer coagulation method, and the processing parameters were optimized according to average particle size and PDI by a single factor experiment. The morphology of the optimized nanoparticles was investigated by TEM, and the in vitro release was carried out to evaluate the optimized HNK-NPs. Results: The encapsulation efficiency and drug loading of the HNK-NPs were 77.75 ± 2.63% and 13.46 ± 0.39%, respectively. The obtained nanoparticles of HNK-NPs were spherical-like under the electron microscope with a mean particle size of 198.50 ± 0.01 nm and a Zeta potential of −52.60 ± 1.00 mV. The in vitro release results showed that the cumulative release rates of nanoparticles were 48.28 ± 9.80% and 81.12 ± 4.35% within 2 h and 8 h, respectively, showing a stable release behavior. The average particle size and PDI of HNK-NPs solution prepared by the hydrophilic polymer condensation method had no obvious change at 72h. Conclusion: HNK-NPs were successfully prepared by the phase separation method. This new polysaccharide polymer should be an ideal carrier to help improve the solubility of HNK.

Introduction: High mortality and limited therapeutic efficacy of clinical treatment make breast cancer a stubborn disease in women. The hypovascular issue is the main challenge needed to be overcome in breast cancer treatment. Methods: For this purpose, hyperthermia-sensitive liposomes containing indocyanine green (ICG) and brucea javanica oil (BJO) (LP(BJO/ICG)) were constructed for near-infrared (NIR) laser-induced photothermal- /chemo-antitumor therapy. ICG, an FDA-approved photothermal agent, was employed in this study to perform photothermal therapy (PTT) effect as well as relieve hypovascular conditions in breast cancer tissue. Results: BJO triggered release from the hyperthermia-sensitive LP (BJO/ICG) due to disassembly of liposomes under the PTT effect caused by ICG under NIR laser irradiation. It was found that mice in LP (BJO/ICG) group showed the slowest tumor growth under NIR laser irradiation, illustrating the strongest antitumor effect among all groups. Conclusion: This responsive-release drug delivery platform can be a promising candidate for the treatment of breast cancer.

Background: Celecoxib is generally used for the treatment of rheumatoid arthritis, however its poor bioavailability and cytotoxicity in pure form have reduced its therapeutic efficacy. This study aims to develop celecoxib liquid suppositories with improved bioavailability and reduced toxicity. Methods: The celecoxib liquid suppositories were prepared by thoroughly mixing celecoxib, poloxamer 188 and poloxamer 407, and tween-20, respectively used as drug, polymers and surfactant, in triple distilled water using cold technique. The developed liquid suppositories were characterized in terms of their gelation temperature, gelation time, and gel strength. Moreover, the muco-adhesive force was determined for the suppositories. The release behavior of the liquid suppositories was investigated in distilled water and compared with drug suspension. Furthermore, pharmacokinetics and morphological studies were carried out in rats after rectal administration of the celecoxib liquid suppository compared with drug suspension. Results: Poloxamer 188 and Tween-20 concentrations have significantly reduced the gelation temperature and time; however, the gel strength and bio-adhesive force were significantly enhanced. The concentration of celecoxib has no significant effect on the properties of liquid suppositories. A significantly enhanced and potentially sustained drug release was observed from the celecoxib liquid suppositories as compared with the drug suspension. The optimized formulation was easy to administer rectally because it quickly forms gel upon insertion into the body due to a suitable gelation temperature of about 31.7 °C. After rectal administration in rats, the celecoxib liquid suppository gave a significantly increased pharmacokinetic profile including enhanced plasma concentration and 9.7 fold improved area under the curve (AUC) compared to the drug suspension. Additionally, the morphology study exhibited no toxicity to the rectal tissue, no signs of irritation, or injury after the application of suppository. However, severe rectal tissue toxicity and irritation was observed in the suspension treated rectum. Conclusion: It can be concluded that the liquid suppository system may significantly enhance the solubilization and bio-availability of sparingly water-soluble drugs as evident in the case of celecoxib with no toxicity at the site of application.