Antipsychotic Potential and Safety Profile of TPGS-Based Mucoadhesive Aripiprazole Nanoemulsion: Development and Optimization for Nose-To-Brain Delivery

Kumbhar, Santosh Ashok; Kokare, Chandrakant; Shrivastava, Birendra; Gorain, Bapi; Choudhury, Hira

doi:10.1016/j.xphs.2021.01.021

Cited by 28 publications

(19 citation statements)

References 60 publications

(92 reference statements)

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“…In the present experiment, three factors at their three levels model was used to optimize the 2 ME mixed micelles. Based on the literature, maximum and minimum levels of the three independent variables, such as phospholipid (Phospholipon 90G), TPGS, and stirring time were fed in the software for identifying the optimized mixed micelles with suitable particle size using the Quality by Design technique (Kumbhar et al, 2021). Based on the information fed in the software, it suggested 15 batches of mixed micelles formulations with a different combination of independent variables at low (−1), medium (0), and high (+1) levels.…”

Section: Experimental Design For Optimization Of Formulation Using Statgraphicsmentioning

confidence: 99%

Development, Optimization and Evaluation of 2-Methoxy-Estradiol Loaded Nanocarrier for Prostate Cancer

et al. 2021

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The therapeutic efficacy of antineoplastic agents possessing a selective target to the nucleus of the cancer cells could be enhanced through novel formulation approaches. Thus, toward the improvement of the anticancer potential of 2-methoxy estradiol (2 ME) on prostate cancer, the drug was entrapped into the hydrophobic micelles core formulated with Phospholipon 90G and d-α-tocopheryl polyethylene glycol succinate (TPGS). Optimization of the formulation was done by Box-Behnken statistical design using Statgraphics software to standardize percentages of TPGS and phospholipid to obtain the smallest particle size. The optimized formulation was found to be spherical with nanometer size of 152 ± 5.2 nm, and low PDI (0.234). The entrapment efficiency of the micelles was 88.67 ± 3.21% with >93% release of 2 ME within 24 h. There was a 16-fold increase in apoptosis and an 8-fold increase in necrosis of the PC-3 cells when incubated with 2 ME micellar delivery compared to control cells (2.8 ± 0.2%). This increased apoptosis was further correlated with increased BAX expression (11.6 ± 0.7) and decreased BCL-2 expression (0.29 ± 0.05) in 2 ME micelles treated cells when compared to the control group. Further, loss of mitochondrial membrane potential (∼50-fold) by the drug-loaded micelles and free drug compared to control cells was found to be due to the generation of ROS. Findings on cell cycle analysis revealed the significant arrest of the G2-M phase of the PC-3 cells when incubated with the optimized formulation. Simultaneously, a significantly increased number of cells in pre-G1 revealed the maximum apoptotic potential of the drug when delivered via micellar formulation. Finally, upregulation of caspase-9, p53, and NO, with downregulation of TNF-α, NF-κβ, and inflammatory mediators of the PC-3 cells established the superiority of the micellar approach against prostate cancer. In summary, the acquired results highlighted the potentiality of the 2 ME-micellar delivery tool for controlling the growth of prostate cancer cells for improved efficacy.

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Section: Experimental Design For Optimization Of Formulation Using Statgraphicsmentioning

confidence: 99%

Development, Optimization and Evaluation of 2-Methoxy-Estradiol Loaded Nanocarrier for Prostate Cancer

et al. 2021

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“…e formulations were developed and the globule size and entrapment efficiency for all the 17 batches were determined following the methodology mentioned in Sections 2.4 and 2.5. e data were incorporated in the response column in the software to obtain the optimized formation. Statistical analysis was performed using analysis of variance (ANOVA) and the effect of the interaction of three independent variables at their different levels on the globule size and entrapment efficiency was analysed from the generated perturbation plots, contour plots, experimental versus predicted plots, and 3D surface plots [25,26]. Quadratic equation generated by the best-fit quadratic model is depicted in…”

Section: Optimization Of Nanoemulsion By Box-behnken Statisticalmentioning

confidence: 99%

Development, Optimization, and Evaluation of Luliconazole Nanoemulgel for the Treatment of Fungal Infection

Alhakamy

Alam³

et al. 2021

Journal of Chemistry

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The present study aimed to optimize luliconazole nanoemulsion using Box–Behnken statistical design, which was further incorporated into the polymeric gel of Carbopol 934. The formulation was characterized for its size, entrapment efficiency, ex vivo permeation, and mechanism of release. The size of the dispersed globules of the optimized drug-loaded nanoemulsion was found to be 17 ± 3.67 nm with a polydispersity index (PDI) less than 0.5. Although the surface charge was recorded at –9.53 ± 0.251, the stability was maintained by the polymeric matrix that prevented aggregation and coalescence of the dispersed globules. The luliconazole-nanoemulgel (LUL-NEG) was characterized for drug content analysis, viscosity, pH, and refractive index, where the results were found to be 99.06 ± 0.59%, 9.26 ± 0.08 Pa.s, 5.65 ± 0.17, and 1.31 ± 0.08, respectively. The permeation across the rat skin was found to be significantly higher with LUL-NEG when compared with LUL gel. Furthermore, the skin irritation test performed in experimental animals revealed that the blank NEG, as well as the LUL-NEG, did not produce any signs of erythema following 48 h exposure. In addition, the histopathological findings of the experimental skins reported no abnormal signs at the formulation application site. Finally, the NEG formulation was found to create a statistically significant zone of inhibition ( P < 0.05) when compared to all other test groups. Overall, it could be summarized that the nanoemulgel approach of delivering luliconazole across the skin to treat skin fungal infections could be a promising strategy.

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“…Various polymers from different categories have been used as mucoadhesive agents in nasal in situ gels. Among them, the Carbopols have been widely used, as they exhibit excellent mucoadhesion strengths at low concentrations and are capable of prolonging the drug release [ 35 ]. The Carbopol 934 polymer that was used in the current study is a polyacrylate polymer with numerous carboxylic groups that is capable of forming hydrogen bonds with nasal mucus membranes, resulting in increased mucoadhesive strength [ 21 ].…”

Section: Resultsmentioning

confidence: 99%

Intranasal Delivery of Darunavir-Loaded Mucoadhesive In Situ Gel: Experimental Design, In Vitro Evaluation, and Pharmacokinetic Studies

Nair

Chaudhary²,

Shah³

et al. 2022

Gels

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The clinical efficacy of antiretroviral therapy in NeuroAIDS is primarily limited by the low perfusion of the drug to the brain. The objective of the current investigation was to design and develop an in situ mucoadhesive gel loaded with darunavir to assess the feasibility of brain targeting through the intranasal route. Preliminary batches (F1–F9) were prepared and evaluated for various pharmaceutical characteristics. A full factorial design of the experiment was applied to optimize and assess the effect of two influencing variables (Carbopol 934P (X1) and Poloxamer 407 (X2)) on the response effects (gelation temperature (Y1) and % drug release (Y2) at 8 h). The data demonstrate that both influencing variables affect the response variables significantly (p < 0.05). The optimized formulation (F7) exhibited favorable rheological properties, adequate mucoadhesion, sustained drug release, and greater permeation across the nasal mucosa. An in vitro ciliotoxicity study confirms the nontoxicity of the optimized in situ gel (D7) on the nasal mucosa. An in vivo pharmacokinetic study in rats was performed to assess drug targeting to the brain following the nasal application of the selected in situ gel (D7). Significantly higher (p < 0.0001) Cmax (~4-fold) and AUC0-α (~3.5-fold) values were noticed in the brain after nasal application, as compared to the intravenous route. However, less systemic exposure to darunavir was noticed with nasal therapy, which confirms the low absorption of the drug into the central compartment. Overall, the data here demonstrate that the optimized in situ mucoadhesive nasal gel is effective in targeting darunavir to the brain by the nasal route and could be a viable option for the treatment of NeuroAIDS.

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Antipsychotic Potential and Safety Profile of TPGS-Based Mucoadhesive Aripiprazole Nanoemulsion: Development and Optimization for Nose-To-Brain Delivery

Cited by 28 publications

References 60 publications

Development, Optimization and Evaluation of 2-Methoxy-Estradiol Loaded Nanocarrier for Prostate Cancer

Development, Optimization and Evaluation of 2-Methoxy-Estradiol Loaded Nanocarrier for Prostate Cancer

Development, Optimization, and Evaluation of Luliconazole Nanoemulgel for the Treatment of Fungal Infection

Intranasal Delivery of Darunavir-Loaded Mucoadhesive In Situ Gel: Experimental Design, In Vitro Evaluation, and Pharmacokinetic Studies

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