trazodone Loaded Lipid core poly (ε-caprolactone) nanocapsules: Development, characterization and in Vivo Antidepressant Effect evaluation nahla elhesaisy 1 & Shady Swidan 1,2* Trazodone hydrochloride (TRH) is a lipophilic drug which is used effectively as an antidepressant. Its poor solubility and short half-life represent an obstacle for its successful use. Nanocapsules with biodegradable polymeric shell are successful drug delivery systems for controlling the release of drugs. to enhance the entrapment of lipophilic drugs, oils can be added forming a lipophilic core in which the drug is more soluble. The aim of this study was to enhance the efficacy of TRH and prolong its action by formulating it into lipid core polymeric shell nanocapsules. Nanocapules were prepared using nanoprecipitation technique. All prepared formulations were in nano size range and negatively charged. The TRH entrapment efficiency (EE%) in lipid core nanocapsules was up to 74.8 ± 0.5% when using Labrafac lipophile as a lipid core compared to only 55.7 ± 0.9% in lipid free polymeric nanospheres. Controlled TRH release was achieved for all prepared formulations. Forced swim test results indicated the significant enhancement of antidepressant effect of the selected TRH loaded Labrafac lipophile core nanocapsules formulation compared to control and TRH dispersion in phosphate buffer. It is concluded that lipid core nanocapsules is a promising carrier for the enhancement of TRH efficacy. Depression is one of the most common, chronic and debilitating psychological disorders that may lead eventually to patient suicide 1. It is characterized by many symptoms like feeling hopelessness or inappropriate guilt, low energy, change in sleep, change in appetite and recurrent thoughts of suicide. Its consequences not only affect the patient, but also affect negatively the whole society. The financial consequences of this disease are tremendous and cause an overwhelming burden on the society. This burden is due to the dramatically decrease in productivity and absenteeism in the workplace. Depression mainly occurred due to the deficiency of both serotonin and norepinephrine neurotransmitters in the brain 2. Trazodone hydrochloride (TRH) is one of the most potent drugs used for the treatment of depression (Fig. 1). It is a triazolopyridine derivative with antidepressant effect 3. It is thought that the mechanism of action of TRH is due to its activity at 5-HT1, 5-HT2 serotonergic receptors. It also acts on poorly blocking serotonin reuptake and selectively blocking presynaptic receptors. In addition, TRH blocks alpha-2 adrenoceptors 4. TRH possesses unique properties compared to other antidepressants. TRH causes fewer anticholinergic side effects compared to the tricyclic antidepressant. It also has an activity against anxiety which is concomitant to depressed patients. Several studies showed that at therapeutic doses TRH is less likely to cause cardiotoxicity than imipramine. TRH also does not result in neurologic side effects and seems to be well tolerat...

Nanostructured lipid carriers (NLC) are a recent approach for the delivery of poorly soluble drugs with low oral bioavailability. The oral antidiabetic Repaglinide (RPG) was loaded into NLC using emulsification-ultrasonification technique. A design of experiment was constructed to study the formulation variables. The influence of the liquid lipid to the solid lipid ratio and the concentration of the surfactant on mean particle size, zeta potential, and drug entrapment efficiency was demonstrated. The mean particle size ranged from 182 ± 7.9 nm to 452 ± 66.1 nm. All particles were negatively charged and the zeta potential values ranged from −7.9 ± 0.9 mV to −44.4 ± 6.2 mV. The highest entrapment efficiency was obtained with the minimum solid lipid to liquid lipid ratio and lowest surfactant concentration. All RPG-NLC formulae showed biphasic time-dependent in vitro release and the studied factors were optimized and the optimum formula was evaluated for in vitro release and crystallinity. The in vitro release of the optimized formula fitted to the Higuchi diffusion model. In conclusion, this study showed the potential of NLC as a carrier for controlled release of RPG.

Anxiety is one of the most prevalent forms of psychopathology that affects millions worldwide. It gained more importance under the pandemic status that resulted in higher anxiety prevalence. Anxiolytic drugs such as benzodiazepines have an unfavorable risk/benefit ratio resulting in a shift toward active ingredients with better safety profile such as the naturally occurring quercetin (QRC). The delivery of QRC is hampered by its low water solubility and low bioavailability. The potential to enhance QRC delivery to the brain utilizing polymeric nanocapsules administered intranasally is investigated in the current study. Polymeric nanocapsules were prepared utilizing the nanoprecipitation technique. The best formula displayed a particle size of 227.8 ± 11.9 nm, polydispersity index of 0.466 ± 0.023, zeta potential of − 17.5 ± 0.01 mV, and encapsulation efficiency % of 92.5 ± 1.9%. In vitro release of QRC loaded polymeric nanocapsules exhibited a biphasic release with an initial burst release followed by a sustained release pattern. Behavioral testing demonstrated the superiority of QRC loaded polymeric nanocapsules administered intranasally compared to QRC dispersion administered both orally and intranasally. The prepared QRC loaded polymeric nanocapsules also demonstrated good safety profile with high tolerability.

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Anxiety is one of the most prevalent forms of psychopathology that affects millions worldwide. It gains more importance under the current pandemic status that resulted in higher anxiety prevalence. Anxiolytic drugs such as benzodiazepines have an unfavorable risk/benefit ratio resulting in a shift toward active ingredients with better safety profile such as the naturally occurring quercetin. The delivery of quercetin is hampered by its low water solubility and low bioavailability. The potential of enhancing quercetin delivery to the brain utilizing polymeric nanocapsules administered nasally is investigated in the current study. Polymeric nanocapsules were prepared utilizing the nanoprecipitation technique. The best formula displayed a particle size of 227.8 ± 11.9, Polydispersity index of 0.466 ± 0.023, zeta potential of -17.5 ± 0.01, and encapsulation efficiency % of 92.5 ± 1.9. The prepared nanoparticles displayed In vitro release of QRC loaded polymeric nanocapsules exhibited a biphasic release with an initial burst release followed by a sustained release pattern. The in vivo evaluation demonstrated the superiority of quercetin polymeric nanocapsules administered intranasally compared quercetin dispersion administered both orally and intranasally. The prepared nanocapsules also demonstrated good safety profile with high tolerability.

Anxiety is one of the most prevalent forms of psychopathology that affects millions worldwide. It gains more importance under the current pandemic status that resulted in higher anxiety prevalence. Anxiolytic drugs such as benzodiazepines have an unfavorable risk/benefit ratio resulting in a shift toward active ingredients with better safety profile such as the naturally occurring quercetin. The delivery of quercetin is hampered by its low water solubility and low bioavailability. The potential of enhancing quercetin delivery to the brain utilizing polymeric nanocapsules administered nasally is investigated in the current study. Polymeric nanocapsules were prepared utilizing the nanoprecipitation technique. The best formula displayed a particle size of 227.8 ± 11.9, Polydispersity index of 0.466 ± 0.023, zeta potential of -17.5 ± 0.01, and encapsulation efficiency % of 92.5 ± 1.9. The prepared nanoparticles displayed In vitro release of QRC loaded polymeric nanocapsules exhibited a biphasic release with an initial burst release followed by a sustained release pattern. The in vivo evaluation demonstrated the superiority of quercetin polymeric nanocapsules administered intranasally compared quercetin dispersion administered both orally and intranasally. The prepared nanocapsules also demonstrated good safety profile with high tolerability.