Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Dec 1;11(12):640.
doi: 10.3390/pharmaceutics11120640.

Attenuation of Benign Prostatic Hyperplasia by Optimized Tadalafil Loaded Pumpkin Seed Oil-Based Self Nanoemulsion: In Vitro and In Vivo Evaluation

Nabil A Alhakamy  1 , Usama A Fahmy  1 , Osama A A Ahmed  1   2
Affiliations

Attenuation of Benign Prostatic Hyperplasia by Optimized Tadalafil Loaded Pumpkin Seed Oil-Based Self Nanoemulsion: In Vitro and In Vivo Evaluation

Nabil A Alhakamy et al. Pharmaceutics. .

Retraction in

Abstract

The FDA has approved tadalafil (TDL) for the treatment of benign prostatic hyperplasia (BPH)-associated symptoms. Pumpkin seed oil (PSO) has shown promise for the relief of prostatitis-related lower urinary tract symptoms. The aim was to improve TDL delivery to the prostate and assess the combined effect of TDL with a PSO-based formula in the management of BPH. PSO, Tween 80, and polyethylene glycol 200 were selected for the optimization of self nano-emulsified drug delivery system (SNEDDS). The formed vesicles were assessed for their globule size and zeta potential. A rat in vivo study was carried out to investigate prostate weight and index, histopathology, and pharmacokinetics. The average globule size for the optimized TDL-PSO SNEDDS was 204.8 ± 18.76 nm, with a zeta-potential value of 7.86 ± 1.21 mV. TDL-PSO SNEDDS produced a marked drop in prostate weight by 35.51% and prostate index by 36.71% compared to the testosterone-only group. Pharmacokinetic data revealed a 2.3-fold increase of TDL concentration, from optimized TDL-PSO SNEDDS, in the prostate compared with the raw TDL group. This study indicated that the combination of TDL and PSO in an optimized TDL PSO SNEDDS formula improved the efficacy of TDL in the management of BPH.

Keywords: PDE5 inhibitors; alternative medicine; hyperplasia; mixture design; noncarcinogenic behavior; pharmacokinetics; prostate enlargement.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Triangular dimensional contour plots for the effect of TDL-PSO SNEDDS components (pumpkin seed oil, surfactant (Tween 80), and co-surfactant (PEG 200)) on globule size (A) and zeta potential (B). TDL-PSO SNEDDS, tadalafil-pumpkin seed oil-self nano-emulsified drug delivery system.
Figure 2
Figure 2
The TEM image of the TDL-PSO SNEDDS vesicles.
Figure 3
Figure 3
Histology of (A) (group 1) ventral lobe of intact rats, H&E, ×40; (B) (group 2) testosterone-induced BPH (benign prostatic hyperplasia) (irregular acinar shape with villous projections of different sizes into the lumen), ×40; (C) (group 3) 14 days of co-administration of testosterone and the plain formula (irregular acinar shape with villous projections of different sizes into the lumen), ×40; (D) (group 4) 14 days of co-administration of testosterone and optimized TDL-PSO SNEDDS (normalized ventral lobe structure), H&E, ×60; (E) (group 5) 14 days of co-administration of testosterone with TDL 2 mg/kg (glands are partially atrophic, with dilated, angular, profiles and adenomatous hyperplasia), H&E, ×60; and (F) (group 6) 14 days of co-administration of testosterone and PSO 100 mg/kg (glands are partially atrophic, with dilated, angular, profiles and adenomatous hyperplasia), H&E, ×60.
Figure 4
Figure 4
Mean ± SD of TDL prostate concentration within 3–18 days after daily subcutaneous (SC) administration of raw TDL and TDL PSO SNEDDS. * Significantly different (p < 0.05) compared to raw TDL.
See this image and copyright information in PMC

References

    1. Amano T., Earle C., Imao T., Matsumoto Y., Kishikage T. Administration of daily 5 mg tadalafil improves endothelial function in patients with benign prostatic hyperplasia. Aging Male. 2018;21:77–82. doi: 10.1080/13685538.2017.1367922. - DOI - PubMed
    1. Damiano R., Cai T., Fornara P., Franzese C.A., Leonardi R., Mirone V. The role of Cucurbita pepo in the management of patients affected by lower urinary tract symptoms due to benign prostatic hyperplasia: A narrative review. Arch. Ital. Di Urol. E Androl. 2016;88:136–143. doi: 10.4081/aiua.2016.2.136. - DOI - PubMed
    1. Egan K.B. The Epidemiology of Benign Prostatic Hyperplasia Associated with Lower Urinary Tract Symptoms: Prevalence and Incident Rates. Urol. Clin. North Am. 2016;43:289–297. doi: 10.1016/j.ucl.2016.04.001. - DOI - PubMed
    1. Vignozzi L., Gacci M., Cellai I., Morelli A., Maneschi E., Comeglio P., Santi R., Filippi S., Sebastianelli A., Nesi G., et al. PDE5 inhibitors blunt inflammation in human BPH: A potential mechanism of action for PDE5 inhibitors in LUTS. Prostate. 2013;73:1391–1402. doi: 10.1002/pros.22686. - DOI - PubMed
    1. Jin S., Xiang P., Liu J., Yang Y., Hu S., Sheng J., He Q., Yu W., Han W., Jin J., et al. Activation of cGMP/PKG/p65 signaling associated with PDE5-Is downregulates CCL5 secretion by CD8 + T cells in benign prostatic hyperplasia. Prostate. 2019;79:909–919. doi: 10.1002/pros.23801. - DOI - PMC - PubMed

Publication types

LinkOut - more resources