Nanoliposomes Embedded Nanocochleates for Codelivery of Artemether and Lumefantrine: An In Vitro and In Vivo Study.

Antimalarial drugs are being encapsulated in nanotechnology-based carriers because there are not enough new treatment options and people are becoming more resistant to the ones that are already available. This approach uses two or more biochemical targets of malarial parasites. The codelivery of artemether and lumefantrine (AL) combines the synergistic effect of artemether for an early onset of action followed by the prolonged effect of lumefantrine. The bioavailability of artemether and lumefantrine is low due to their low solubility. Thus, an alternative lipidic formulation, namely nanocochleate, was developed for the selected drugs by adding calcium ions into preformed nanoliposomes (AL-loaded liposomes). Using phospholipon 90H and cholesterol, a thin-film hydration method produced drug-loaded liposomes. The synthesized AL-loaded liposomes were further incorporated into nanocochleates. The formulations were evaluated for in vitro and in vivo parameters. Nanocochleates had a particle size of 200.7 nm, a zeta potential of -9.4 mV, and an entrapment efficiency of 73.12% ± 1.82% and 61.46% ± 0.78%, respectively, for artemether and lumefantrine. Whereas liposomes had a particle size of 210 nm and an entrapment efficiency of 67.34% ± 1.52% and 53.24% ± 0.78%, respectively, for artemether and lumefantrine. An X-ray diffraction study confirmed the amorphous state of artemether and lumefantrine in liposomes and nanocochleate. Nanocochleate showed a controlled release profile for loaded drugs. When compared with free drugs, nanocochleate showed low tissue distribution and a 20-fold increase in bioavailability in rats. Thus, nanocochleate offers an interesting alternative to an existing dosage form for the treatment of malaria.

Preparation and Optimization of Liposome Containing Thermosensitive In Situ Nasal Hydrogel System for Brain Delivery of Sumatriptan Succinate.

Drug absorption is improved by the intranasal route's wide surface area and avoidance of first-pass metabolism. For the treatment of central nervous system diseases such as migraine, intranasal administration delivers the medication to the brain. The study's purpose was to develop an in situ nasal hydrogel that contained liposomes that were loaded with sumatriptan succinate (SS). A thin-film hydration approach was used to create liposomes, and a 32 factorial design was used to optimize them. The optimized liposomes had a spherical shape, a 171.31 nm particle size, a high drug encapsulation efficiency of 83.54%, and an 8-h drug release of 86.11%. To achieve in situ gel formation, SS-loaded liposomes were added to the liquid gelling system of poloxamer-407, poloxamer-188, and sodium alginate. The final product was tested for mucoadhesive strength, viscosity, drug content, gelation temperature, and gelation time. Following intranasal delivery, in vivo pharmacokinetic investigations showed a significant therapeutic concentration of the medication in the brain with a Cmax value of 167 ± 78 ng/mL and an area under the curve value of 502 ± 63 ng/min·mL. For SS-loaded liposomal thermosensitive nasal hydrogel, significantly higher values of the nose-to-brain targeting parameters, that is, drug targeting index (2.61) and nose-to-brain drug direct transport (57.01%), confirmed drug targeting to the brain through the nasal route. Liposomes containing thermosensitive in situ hydrogel demonstrated potential for intranasal administration of SS.

Formulation and Characterization of Nanostructured Lipid Carriers of Rizatriptan Benzoate-Loaded In Situ Nasal Gel for Brain Targeting.

Intranasal route provides large surface area, avoids first-pass metabolism, and results in improved drug absorption. Intranasal delivery targets the drug to the brain for treatment of central nervous diseases viz migraine. The objective of the study was to formulate in situ nasal gel containing rizatriptan benzoate (RB)-loaded nanostructured lipid carriers (NLCs). NLCs were prepared by melt-emulsification ultrasonication method and optimized using 32 factorial design. Optimized NLCs were spherical with particle size of 189 nm, high drug encapsulation efficiency (84.5%), and 83.9% drug release at the end of 24 h. RB-loaded NLCs were incorporated into the liquid Carbopol 934P and Poloxamer 407 liquid gelling system to obtain in situ gel formation. The resultant product was assessed for gelling capacity, viscosity, and mucoadhesive strength. In vivo pharmacokinetic studies revealed significant therapeutic concentration of drug in the brain following intranasal administration with Cmax value of 5.1 ng/mL and area under the curve value of 829 ng/(min·mL). Significantly higher values of nose to brain targeting parameters, namely, drug targeting index (2.76) and nose to brain drug direct transport (63.69%) for RB-NLCs in situ nasal gel, confirmed drug targeting to brain through nasal route. The ex vivo nasal toxicity study showed no sign of toxicity to the nasal mucosa. Thus, the application of lipid carrier-loaded in situ gel proved potential for intranasal delivery of RB over the conventional gel formulations for efficient brain targeting.

Skin Targeting of Oxiconazole Nitrate Loaded Nanostructured Lipid- Carrier Gel for Fungal Infections.

BACKGROUND: The progression of fungal infections can be rapid and serious due to compromising with immune function. They may cause liver damage, affect estrogen levels or may cause allergic reactions. Oxiconazole nitrate (OXZN) is a broad spectrum commonly used antifungal drug. It acts by erogosterol biosynthesis inhibition, which causes lysis of the fungal cell membrane because of changes in both membrane integrity and fluidity and direct membrane damage of fungal cells. However, its poor water solubility and short half-life (3-5 h) limit its applications. OBJECTIVE: This study aimed to develop and evaluate OXZN-loaded nanostructured lipid carrier (NLC) to improve its solubility and prolong its release for the treatment of fungal infection via topical administration. METHOD: OXZN-NLC was prepared by ultrasonication method using 32 full factorial design. Glyceryl monostearate (GMS) (X1) and oleic acid (X2) were used as independent variables and particle size and percentage entrapment efficiency (% EE) as dependent variables. The OXZN-NLCs were characterized for particle size, particle morphology and entrapment efficiency. RESULTS: The mean diameter of optimized OXZN-NLCs was found to be 124 ± 2 nm. Spherical shape and size were confirmed using scanning electron microscopy (SEM). Skin deposition study showed about 82.74% deposition as compared with the marketed formulation that showed 68.42% deposition. The developed NLCs show a sustained release pattern and high drug disposition in the infected area. CONCLUSION: OXZN-NLC could be a potential alternative for the treatment of topical fungal infection after clinical evaluation in near future.