Natural ergot alkaloids in ocular pharmacotherapy: known molecules for novel nanoparticle-based delivery systems

Several pharmacological properties are attributed to ergot alkaloids as a result of their antibacterial, antiproliferative, and antioxidant effects. Although known for their biomedical applications (e.g., for the treatment of glaucoma), most ergot alkaloids exhibit high toxicological risk and may even be lethal to humans and animals. Their pharmacological profile results from the structural similarity between lysergic acid-derived compounds and noradrenalin, dopamine, and serotonin neurotransmitters. To reduce their toxicological risk, while increasing their bioavailability, improved delivery systems were proposed. This review discusses the safety aspects of using ergot alkaloids in ocular pharmacology and proposes the development of lipid and polymeric nanoparticles for the topical administration of these drugs to enhance their therapeutic efficacy for the treatment of glaucoma.This work was supported by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) granted to I.B. (88887.368385/2019-00), by the Portuguese Science and Technology Foundation (FCT) and co-financed by FEDER, under the Partnership Agreement PT2020, granted to E.B.S. (UIDB/04469/2020 strategic fund), by the Nutraceutica come supporto nutrizionale nel paziente oncologico, project granted to A.S. (CUP: B83D18000140007), and by Foundation of Research Support of the São Paulo State (FAPESP) for the funded projects 2011/10333-1, 2012/03427-2, and 2018/26069-0 and for the National Council for Scientific and Technological Development (CNPq) granted to W.P.O.info:eu-repo/semantics/publishedVersio

A Fresh Look on Bergenin: Vision of Its Novel Drug Delivery Systems and Pharmacological Activities

Bergenin (BER), a key constituent of Bergenia crassifolia (Saxifragaceae), has gained extensive attention, owing to its array of pharmacological actions, including anti-infective, anti-cancer, anti-diabetic, neuroprotective, hepatoprotective, anti-urolithiatic, anti-hyperuricemic, and anti-bradykinin properties. Despite ever-intensifying support for its therapeutic features, the poor solubility, lower oral bioavailability, shorter half-life, and more intestinal pH degradation (pH 6.8 or above) of BER have puzzled researchers. To circumvent these pharmaceutical challenges, and to improve its therapeutic efficacy, newer approaches have been adopted by research scientists. Thus, a discussion of the existing literature may provide complete information about the advances in delivery strategies for enhancing its utility. This paper summarizes up-to-date works on the design and development of novel delivery carriers of this bioactive compound, such as phospholipid complexes, extended-release core tablets, prodrugs, herbal gels, polyherbal ointments, nanoparticles, and poly (lactic acid) polymers, with the objective of harnessing its full potential. This review also provides a deep insight into its bioactivities, along with mechanisms. Additionally, the physicochemical attributes, chemistry, and pharmacokinetics of BER are discussed herein. Hence, the comprehensive information documented in this review may introduce new avenues for research advancements of BER

Formulation, Characterization, Anti-Inflammatory and Cytotoxicity Study of Sesamol-Laden Nanosponges

Sesamol (SES) possesses remarkable chemotherapeutic activity, owing to its anti-inflammatory and antioxidant potential. However, the activity of SES is mainly hampered by its poor physicochemical properties and stability issues. Hence, to improve the efficacy of this natural anti-inflammatory and cytotoxic agent, it was loaded into β-cyclodextrin nanosponges (NS) prepared using different molar ratios of polymer and crosslinker (diphenyl carbonate). The particle size of SES-laden NS (SES-NS) was shown to be in the nano range (200 to 500 nm), with a low polydispersity index, an adequate charge (−17 to −26 mV), and a high payload. Field emission scanning electron microscopy, thermogravimetric analysis, and Fourier transform infrared spectroscopy were used to characterize the bioactive-loaded selected batch (SES-NS6). This batch of nanoformulations showed improved solubilization efficacy (701.88 µg/mL) in comparison to bare SES (244.36 µg/mL), polymer (β-CD) (261.43 µg/mL), and other fabricated batches. The drug release data displayed the controlled release behavior of SES from NS. The findings of the egg albumin denaturation assay revealed the enhanced anti-inflammatory potential of SES-NS as compared to bare SES. Further, the cytotoxicity assay showed that SES-NS was more effective against B16F12 melanoma cell lines than the bioactive alone. The findings of this assay demonstrated a reduction in the IC50 values of SES-NS (67.38 μg/mL) in comparison to SES (106 μg/mL). The present investigation demonstrated the in vitro controlled release pattern and the enhanced anti-inflammatory and cytotoxic activity of SES-NS, suggesting its potential as a promising drug delivery carrier for topical delivery