Trazodone Loaded Lipid Core Poly (ε-caprolactone) Nanocapsules: Development, Characterization and in Vivo Antidepressant Effect Evaluation

Abstract

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...

Polymeric versus lipid nanocapsules for miconazole nitrate enhanced topical delivery: in vitro and ex vivo evaluation

“…The results in Table 2 also revealed that the %EE values for LNCs (F4, F5, and F6) were higher than PNCs (F1, F2, and F3) and this could be related to the inclusion of lipids in the core of nanocapsules structure where highly lipophilic drugs could be concentrated in (El-Hesaisy & Swidan, 2020 ). As well as they donate thick shell for nanocapsules; allow higher amount of drug entrapment as well as slower release (Radwan et al., 2020 ).…”

“…The negative zeta potential of LNCs (–25.23 ± 3.72 to −33.22 ± 2.1) may be attributed to the amphiphilic surfactant soy phosphatidylcholine as well as presence of oleic acid in the oil core which has strong negative charge (Xia et al., 2017 ; El-Hesaisy & Swidan, 2020 ). Consequently, by increasing lipid content with respect to MN, zeta potential increased ( Table 2 ).…”

“…Pure MN displayed a continuous release of the same amount of drug per unit time (zero order) which correlated to its lipophilicity that is characterized by release kinetics of this nature (Rodrigues et al., 2020 ). In turn, PNCs (F1) are best fitted to Higuchi’s diffusion model where the drug released from the nanocapsules after the degradation of thin polymeric outer shell membrane is governed by the slow diffusion of MN from the viscous PCL matrix rather than erosion mechanism (El-Hesaisy & Swidan, 2020 ). Moreover, the LNCs (F6) were fixed to the Baker and Lonsdale model which designates controlled drug release manner from spherical-core shell matrices combined with diffusion (Mircioiu et al., 2019 ).…”

“…The most commonly used polymers for forming the shell are biocompatible and biodegradable such as poly lactic acid, polylactide-co-glycolide, and poly (Ɛ-caprolactone). Polycaprolactone (PCL) is widely used to prepare different types of nanocapsules comparing to other biodegradable polymers owing to its talented characters; safety, elasticity, cytocompatibility, and very slow biodegradation which were approved by US-FDA (El-Hesaisy & Swidan, 2020 ; Rahat et al., 2021 ). It is also useful to capture a wide range of drugs such as anti-cancer drugs, anti-inflammatories, and immune modulators presenting diverse flexibility with potential applications in therapy (Mahareek et al., 2019 ).…”

Assessing the Synergistic Activity of Clarithromycin and Therapeutic Oils Encapsulated in Sodium Alginate Based Floating Microbeads

“…Many studies have reported variation in the entrapment efficiency of active ingredients in carriers using various lipids or oils. This is because drugs demonstrate a variable solubility in these lipids and oils [37,38].…”