Freeze-dried chitosan nanoparticles to stabilize and deliver bromelain

Ataide, Janaína Artem; Geraldes, Danilo Costa; Gérios, Eloah Favero; Bissaco, Fernanda Mazon; Cefali, Letícia Caramori; Mazzola, Priscila Gava

doi:10.1016/j.jddst.2020.102225

Cited by 20 publications

(23 citation statements)

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“…Despite increase in PDI observed in C-B-NP compared with C-NP, both nanoparticles could be considered moderately polydisperse (PDI values between 0.1 and 0.4 31 ). Encapsulation efficiency of C-B-NP was in accordance with previous reported results 27 , 28 . Protein release kinetics was not performed due to previous reported instability in relevant physiological medium overtime by other authors and our group 28 .…”

Section: Discussionsupporting

confidence: 92%

“…Encapsulation efficiency of C-B-NP was in accordance with previous reported results 27 , 28 . Protein release kinetics was not performed due to previous reported instability in relevant physiological medium overtime by other authors and our group 28 . In this same study 28 , TEM characterization of NP were performed and reported.…”

Section: Discussionsupporting

confidence: 92%

“…C-B-NP characterization was in accordance with our previously reported data 27 , 28 . Decrease in zeta potential can be attributed to the bromelain surface's negative charge at pH 5.0 30 , which promotes electrostatic interaction between chitosan and bromelain, with a consequent decrease in free positive chitosan groups.…”

Section: Discussionsupporting

confidence: 88%

“…Protein release kinetics was not performed due to previous reported instability in relevant physiological medium overtime by other authors and our group 28 . In this same study 28 , TEM characterization of NP were performed and reported. Under TEM observation, particles presented spherical shape, with small particles aggregated in 100 nm agglomerates.…”

Section: Discussionmentioning

confidence: 99%

“…Several different methods have been used to prepare chitosan nanoparticles, but ionotropic gelation is often favored, as it is a simple, mild, and controllable process 26 . In addition, bromelain has already been successfully encapsulated in chitosan nanoparticles by our group 27 , 28 .…”

Section: Introductionmentioning

confidence: 99%

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In vitro performance of free and encapsulated bromelain

Ataide

Cefali

Figueiredo

et al. 2021

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For centuries, bromelain has been used to treat a range of ailments, even though its mechanism of action is not fully understood. Its therapeutic benefits include enzymatic debridement of the necrotic tissues of ulcers and burn wounds, besides anti-inflammatory, anti-tumor, and antioxidant properties. However, the protease is unstable and susceptible to self-hydrolysis over time. To overcome the stability issues of bromelain, a previous study formulated chitosan-bromelain nanoparticles (C-B-NP). We evaluated the optimized nanoformulation for in vitro antioxidant, cell antiproliferative activities and cell migration/proliferation in the scratch assay, comparing it with free bromelain. The antioxidant activity of free bromelain was concentration and time-dependent; after encapsulation, the activity level dropped, probably due to the slow release of protein from the nanoparticles. In vitro antiproliferative activity was observed in six tumor cell lines for free protein after 48 h of treatment (glioma, breast, ovarian, prostate, colon adenocarcinoma and chronic myeloid leukemia), but not for keratinocyte cells, enabling its use as an active topical treatment. In turn, C-B-NP only inhibited one cell line (chronic myeloid leukemia) and required higher concentrations for inhibition. After 144 h treatment of glioma cells with C-B-NP, growth inhibition was equivalent to that promoted by the free protein. This last result confirmed the delayed-release kinetics of the optimized formulation and bromelain integrity. Finally, a scratch assay with keratinocyte cells showed that C-B-NP achieved more than 90% wound retraction after 24 h, compared to no retraction with the free bromelain. Therefore, nanoencapsulation of bromelain with chitosan conferred physical protection, delayed release, and wound retraction activity to the formulation, properties that favor topical formulations with a modified release. In addition, the promising results with the glioma cell line point to further studies of C-B-NP for anti-tumor treatments.

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