Pharmaceutical Nanotechnology - Volume 10, Issue 2, 2022

According to the interaction of nanoparticles with biological systems, enthusiasm for nanotechnology in biomedical applications has been developed in the past decades. Fe2O3 nanoparticles, as the most stable iron oxide, have special merits that make them useful widely for detecting diseases, therapy, drug delivery, and monitoring the therapeutic process. This review presents the fabrication methods of Fe2O3-based materials and their photocatalytic and magnetic properties. Then, we highlight the application of Fe2O3-based nanoparticles in diagnosis and imaging, different therapy methods, and finally, stimulus-responsive systems, such as pH-responsive, magneticresponsive, redox-responsive, and enzyme-responsive, with an emphasis on cancer treatment. In addition, the potential of Fe2O3 to combine diagnosis and therapy within a single particle called theranostic agent will be discussed.

Background: Hydrophilic drugs are poor applicants for brain targeting via oral route due to the presence of a blood-brain barrier that allows only small lipophilic molecules to freely access the brain. Due to unique anatomical connections between the nasal cavity and the brain, intranasal administration can be explored for drug delivery to the brain directly that circumvents the blood-brain barrier too. Objectives: Zolmitriptan is a widely used antimigraine drug, and its brain targeting by nasal route in the form of mucoadhesive nanoparticles is more effective in migraine treatment as it provides fast relief and good bioavailability as compared to its oral drug delivery. In the present study, zolmitriptan mucoadhesive nanoparticles were prepared to improve the bioavailability and brain targeting for the better management of Migraine attacks. Methods: The mucoadhesive polymeric nanoparticles of zolmitriptan were formulated by a modified ionic gelation method using thiolated chitosan. The pharmacokinetic parameters were counted in male Wistar rats by intranasal and oral delivery of the anti-migraine drug zolmitriptan and compared statistically. The concentration of zolmitriptan in the blood plasma and brain samples was determined by using the liquid-liquid extraction method followed by a reversed-phase highperformance liquid chromatography (RP-HPLC) analysis. The pharmacodynamic analysis was conducted in adult male Swiss albino mice by behavioral models, a light/dark box model, and acetic acid-induced writhing (abdominal stretching or constriction). These tests were used to reproduce the important associated symptoms of migraine viz. hyperalgesia (nociceptive sensitization) and photophobia to assess the therapeutic potential of intranasal delivery of nanoparticles antimigraine activity. Results: The absolute bioavailability accessed for Zolmitriptan nanoparticles by IN route was found to be very high (193%), suggesting that the sufficient amount of drug transported by nanoparticles and DTE ratio was calculated as 2.8. Moreover, it revealed better nose-to-brain transport by zolmitriptan nanoparticles as compared to oral delivery in male Wistar rats. A significant increase in the tolerance capacity of animals to bright light and a fall in the number of stretching in mice suggested the better management of migraine-associated symptoms by the zolmitriptan nanoparticles. Conclusion: Thus, the present study confers the significance of nasal drug delivery for brain targeting of zolmitriptan nanoparticles for the treatment of migraine.

Background: The proposed study was aimed to formulate and evaluate the glipizidephospholipid nano-complex. Since glipizide is a poorly soluble drug, its complexation with phospholipids is an ideal approach to improving solubility. Methods: To improve the oral potency of glipizide, its phospholipid complex was prepared by employing the solvent evaporation method. The formulations were characterized using DSC, FTIR, PXRD, SEM, TEM, and hot stage microscopy (HSM). Solubility tests of the glipizidephospholipid nano-complex revealed a significant increase in aqueous solubility compared to glipizide's physical combination. The oral bioavailability of the glipizide-phospholipid nanocomplex was measured by using HPLC in Wistar rats’ plasma. FTIR and PXRD results revealed no significant interaction between the drug and the phospholipid in the formulation. SEM and TEM studies confirmed the morphology of the formulation assuring the conversion of crystalline form into an amorphous structure. Results: The glipizide-phospholipid nano-complex had a greater peak plasma concentration (5.2 vs. 3.8 g/mL), a larger AUC (26.31 vs. 19.55 μgh/L), and a longer T1/2 (2.1 vs. 4.1 h) than free glipizide, indicating that it improved drug dissolution rate. Conclusion: The outcomes suggested that a phospholipid complexation is a potential approach to increasing water-insoluble drugs' oral bioavailability.

Introduction: Paraquat (PQ), as a bipyridyl compound, is widely used as an effective herbicide that produces reactive oxygen species (ROS), affecting the unsaturated lipids of cell membranes leading to cell mortality. N-acetylcysteine (NAC) is a medication that has a beneficial role in reducing the intoxication of kidneys caused by PQ. Niosomes are bilayer vesicles that enhance the bioavailability of drugs. This study aimed to compare the effects of NAC and niosome of NAC (NACNPs) on PQ-induced kidney toxicity concerning its antioxidant activity. Methods: In this experimental study, after formulating NACNP, 30 Wistar male rats weighing 180 to 250 gm were classified into five groups: the control group was treated with normal saline, while the other four groups received 35mg/kg/day of PQ via intraperitoneal route and, was treated with 25mg/kg/day NAC, 25mg/kg/day niosome and 25 mg/kg/day NACNP by gavage, Then, oxidative stress biomarkers such as total antioxidant capacity (TAC), catalase activity (CAT), lipid peroxidation (LPO), and total thiol group (TTG), plus blood urea nitrogen (BUN) and creatinine levels were evaluated in kidney tissue homogenate and examined histopathologically. Results: The results revealed that TTG increased significantly in NAC & NACNP groups than in the PQ group. Further, in the PQ group, LPO increased significantly compared with the control, NAC, and NACNP groups, while in the NAC and NACNP group, LPO diminished compared with the PQ group. There was no significant difference in TAC between groups. Blood urea nitrogen (BUN) and creatinine levels dropped in NACNP compared with the PQ group and the NAC. Histological studies also approved PQ-induced damage and the protective effect of NACNP. Conclusion: The results indicated that NACNP could modulate oxidative stress status and kidney function against PQ toxicity.

Aims: In this study, four fluorescein hydrophobic ionic complexes were formed with the cationic polymers Eudragit RS, Eudragit RL, Eudragit E, and polyethyleneimine (PEI) to provide fluorescein sustained release, sustained cellular uptake, and stability. Methods: Complexes were loaded in a self-emulsifying drug delivery system (SEDDS) composed of 40% Tween 80, 20% Kolliphor EL, 15% 2-n-Octyl-1-dodecanol, and 25% dipropylene glycol. SEDDS were investigated regarding their size, polydispersity index (PDI), zeta potential, and cytotoxicity. Fluorescein release from SEDDS was performed in phosphate buffer (pH 6.8 and pH 8), and the released fluorescein was evaluated for cellular uptake. Moreover, fluorescein from all of the SEDDS pre-concentrates was released at different time points to check its long-term stability over six months. Results: The average fluorescein load in SEDDS was 0.045%. SEDDS showed an average droplet size of 24.9 ± 1.6 nm with PDI ≤ 0.3. SEDDS complexes diluted 1:100 increased the zeta potential from -7.3 mV to +3.7 mV and provided > 85% cell viability. A 92.27 ± 3.18% fluorescein exhibited a few seconds of immediate release when used as control or PEI complex in SEDDS. On the contrary, Eudragit-fluorescein complexes in SEDDS showed sustained release of 87.01 ± 5.22% fluorescein in ≤ 70 min with 22.19 ± 14.56% and 59.27 ± 16.57% released at 10 min in pH 6.8 and pH 8 release media, respectively. Comparatively, the medium at pH 6.8 maintained a significantly improved sustained fluorescein release (p ≤ 0.001). Furthermore, Eudragit RS/RL compared to Eudragit E, significantly exhibited a slower fluorescein release rate from SEDDS (p ≤ 0.01). The cellular uptake of the released fluorescein was 72.4 ± 8.2% for all SEDDS complexes after 3 h. Eudragit complexes compared to PEI complex in SEDDS significantly showed m ore sustained fluorescein cellular uptake at 1 h and 2 h (p ≤ 0.001). However, SEDDS complexes showed the longest fluorescein stability with PEI after six months, whereas fluorescein stability for SEDDS containing fluorescein as Eudragit complex and control showed 39.1% and 82.5% fluorescence decrease, respectively, after three months. Conclusion: In the developed SEDDS, the presence of hydrophobic ionic complexes can significantly promote longer stability and sustained cellular uptake of fluorescein while releasing in a sustained manner.