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Journal ArticleDOI

D-α-Tocopherol-Based Micelles for Successful Encapsulation of Retinoic Acid.

04 Mar 2021-Pharmaceuticals, policy and law (Multidisciplinary Digital Publishing Institute)-Vol. 14, Iss: 3, pp 212
TL;DR: In this article, a solubility study based on the equilibrium method was performed; then, six ATRA-TPGS formulations were prepared by the solvent-casting method using different TPGS amounts.
Abstract: All-trans-retinoic acid (ATRA) represents the first-choice treatment for several skin diseases, including epithelial skin cancer and acne. However, ATRA’s cutaneous side effects, like redness and peeling, and its high instability limit its efficacy. To address these drawbacks and to improve ATRA solubilization, we prepared ATRA-loaded micelles (ATRA-TPGSs), by its encapsulation in D-α-tocopheryl-polyethylene-glycol-succinate (TPGS). First, to explore the feasibility of the project, a solubility study based on the equilibrium method was performed; then, six ATRA-TPGS formulations were prepared by the solvent-casting method using different TPGS amounts. ATRA-TPGSs showed small sizes (11–20 nm), low polydispersity, slightly negative zeta potential, and proved good encapsulation efficiency, confirmed by a chemometric-assisted Fourier transform infrared spectroscopy (FTIR) investigation. ATRA-TPGS stability was also investigated to choose the most stable formulation. Using Carbopol® 980 as gelling agent, ATRA-TPGS-loaded gels were obtained and analyzed for their rheological profiles. Ex vivo release studies from ATRA-TPGSs were performed by Franz cells, demonstrating a permeation after 24 h of 22 ± 4 µ cm−2. ATRA-TPGSs showed enhanced cytotoxic effects on melanoma cells, suggesting that these formulations may represent a valid alternative to improve patient compliance and to achieve more efficacious therapeutic outcomes.
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Journal ArticleDOI
TL;DR: In this article, the authors investigated the suitability of TPGS to encapsulate RES in micelles by means of a phase-solubility study, then RES-TPGS formulations were prepared via solvent casting and solvent diffusion evaporation methods.
Abstract: Children affected by chronic liver disease exhibit impaired neurocognitive development and growth due to the low absorption and digestion of nutrients. Furthermore, malnutrition is an adverse prognostic factor in liver transplantation as it is associated with an increase in morbidity and mortality. D-α-tocopheryl-polyethylene-glycol-succinate (TPGS) is currently administered per os as a vitamin E source to improve children’s survival and well-being; however, TPGS alone does not reverse spinocerebellar degeneration and lipid peroxidation. To potentiate the effects of TPGS, we loaded micelles with resveratrol (RES), a natural polyphenol, with antioxidant and antiinflammatory activities, which has demonstrated protective action in the liver. Firstly, we investigated the suitability of TPGS to encapsulate RES in micelles by means of a phase-solubility study, then RES-TPGS formulations were prepared via solvent casting and solvent diffusion evaporation methods. RES-TPGS colloidal dispersions showed small mean diameters (12 nm), low polydispersity, and quite neutral Zeta potentials. The formulations showed a sustained drug release and a good drug loading capacity, further confirmed by infrared spectroscopy and differential scanning calorimetry. RES-TPGSs exhibited unaltered antioxidant activity compared to pristine RES via the DPPH assay and a significant reduction in toxicity compared to empty TPGS on HaCaT cells. Thus, RES-TPGS micelles may overcome the challenges of current liver disease therapy by providing more protective effects thanks to the antioxidant activity of RES and by reducing the surfactant toxicity on normal cells.

20 citations

Journal ArticleDOI
TL;DR: In this paper, the authors summarized current evidence on retinoids' efficacy as antifungal agents and identified studies published in the English language and reference lists of respective articles from 1946 to today.
Abstract: Retinoids—a class of chemical compounds derived from vitamin A or chemically related to it—are used especially in dermatology, oncohematology and infectious diseases. It has been shown that retinoids—from their first generation—exert a potent antimicrobial activity against a wide range of pathogens, including bacteria, fungi and viruses. In this review, we summarize current evidence on retinoids’ efficacy as antifungal agents. Studies were identified by searching electronic databases (MEDLINE, EMBASE, PubMed, Cochrane, Trials.gov) and reference lists of respective articles from 1946 to today. Only articles published in the English language were included. A total of thirty-nine articles were found according to the criteria. In this regard, to date, In vitro and In vivo studies have demonstrated the efficacy of retinoids against a broad-spectrum of human opportunistic fungal pathogens, including yeast fungi that normally colonize the skin and mucosal surfaces of humans such as Candida spp., Rhodotorula mucilaginosa and Malassezia furfur, as well as environmental moulds such as Aspergillus spp., Fonsecae monofora and many species of dermatophytes associated with fungal infections both in humans and animals. Notwithstanding a lack of double-blind clinical trials, the efficacy, tolerability and safety profile of retinoids have been demonstrated against localized and systemic fungal infections.

20 citations

Journal ArticleDOI
TL;DR: In this paper , the role of various inorganic, polymer, and lipid-based nanoparticles in skin cancer therapy with subsequent descriptions of their patents and clinical trials is discussed, followed by their current treatment modalities and associated drawbacks.
Abstract: Abstract Skin cancer has emerged as the fifth most commonly reported cancer in the world, causing a burden on global health and the economy. The enormously rising environmental changes, industrialization, and genetic modification have further exacerbated skin cancer statistics. Current treatment modalities such as surgery, radiotherapy, conventional chemotherapy, targeted therapy, and immunotherapy are facing several issues related to cost, toxicity, and bioavailability thereby leading to declined anti-skin cancer therapeutic efficacy and poor patient compliance. In the context of overcoming this limitation, several nanotechnological advancements have been witnessed so far. Among various nanomaterials, nanoparticles have endowed exorbitant advantages by acting as both therapeutic agents and drug carriers for the remarkable treatment of skin cancer. The small size and large surface area to volume ratio of nanoparticles escalate the skin tumor uptake through their leaky vasculature resulting in enhanced therapeutic efficacy. In this context, the present review provides up to date information about different types and pathology of skin cancer, followed by their current treatment modalities and associated drawbacks. Furthermore, it meticulously discusses the role of numerous inorganic, polymer, and lipid-based nanoparticles in skin cancer therapy with subsequent descriptions of their patents and clinical trials. Graphical Abstract

20 citations

Journal ArticleDOI
TL;DR: Water-soluble formulations of the pyrazole derivative 3-(4-chlorophenyl)-5-nitrophenylamino)-1H-pyrazole-4-carbonitrile (CR232), which were proven to have in vitro antiproliferative effects on different cancer cell lines, were prepared by two diverse nanotechnological approaches.
Abstract: Water-soluble formulations of the pyrazole derivative 3-(4-chlorophenyl)-5-(4-nitrophenylamino)-1H-pyrazole-4-carbonitrile (CR232), which were proven to have in vitro antiproliferative effects on different cancer cell lines, were prepared by two diverse nanotechnological approaches. Importantly, without using harmful organic solvents or additives potentially toxic to humans, CR232 was firstly entrapped in a biodegradable fifth-generation dendrimer containing lysine (G5K). CR232-G5K nanoparticles (CR232-G5K NPs) were obtained with high loading (DL%) and encapsulation efficiency (EE%), which showed a complex but quantitative release profile governed by Weibull kinetics. Secondly, starting from hydrogenated soy phosphatidylcholine and cholesterol, we prepared biocompatible CR232-loaded liposomes (CR232-SUVs), which displayed DL% and EE% values increasing with the increase in the lipids/CR232 ratio initially adopted and showed a constant prolonged release profile ruled by zero-order kinetics. When relevant, attenuated total reflectance Fourier transformed infrared spectroscopy (ATR-FTIR) and nuclear magnetic resonance (NMR) spectroscopy, scanning electron microscopy (SEM) and dynamic light scattering (DLS) experiments, as well as potentiometric titrations completed the characterization of the prepared NPs. CR232-G5K NPs were 2311-fold more water-soluble than the pristine CR232, and the CR232-SUVs with the highest DL% were 1764-fold more soluble than the untreated CR232, thus establishing the success of both our strategies.

16 citations

Journal ArticleDOI
TL;DR: In this article, a new water-soluble BBB4-based nano-formulation was developed by its physical entrapment in a biodegradable non-cytotoxic cationic dendrimer (G4K), without recovering harmful solvents as DMSO or surfactants.
Abstract: 2-(4-Bromo-3,5-diphenyl-pyrazol-1-yl)-ethanol (BBB4) was synthetized and successfully evaluated concerning numerous biological activities, except for antimicrobial and cytotoxic effects. Due to the antimicrobial effects possessed by pyrazole nucleus, which have been widely reported, and the worldwide need for new antimicrobial agents, we thought it would be interesting to test BBB4 and to evaluate its possible antibacterial effects. Nevertheless, since it is water-insoluble, the future clinical application of BBB4 will remain utopic unless water-soluble BBB4 formulations are developed. To this end, before implementing biological evaluations, BBB4 was herein re-synthetized and characterized, and a new water-soluble BBB4-based nano-formulation was developed by its physical entrapment in a biodegradable non-cytotoxic cationic dendrimer (G4K), without recovering harmful solvents as DMSO or surfactants. The obtained BBB4 nanoparticles (BBB4-G4K NPs) showed good drug loading (DL%), satisfying encapsulation efficiency (EE%), and a biphasic quantitative release profile governed by first-order kinetics after 24 h. Additionally, BBB4-G4K was characterized by ATR-FTIR spectroscopy, NMR, SEM, dynamic light scattering analysis (DLS), and potentiometric titration experiments. While, before the nanotechnological manipulation, BBB4 was completely water-insoluble, in the form of BBB4-G4K NPs, its water-solubility resulted in being 105-fold higher than that of the pristine form, thus establishing the feasibility of its clinical application.

16 citations

References
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Journal ArticleDOI
TL;DR: TPGS properties as a P-gp inhibitor, solubilizer/absorption and permeation enhancer in drug delivery and TPGS-related formulations such as nanocrystals, nanosuspensions, tablets/solid dispersions, adjuvant in vaccine systems, nutrition supplement, plasticizer of film, anticancer reagent and so on are discussed.

437 citations

Journal ArticleDOI
TL;DR: Results showed that negatively charged liposomes strongly improved newborn pig skin hydration and TRA retention, though no evidence of intact vesicle penetration was found, and may be an interesting carrier for tretinoin in skin disease treatment, when appropriate formulations are used.

283 citations

Journal ArticleDOI
TL;DR: The recent advances of TPGS in drug delivery including T PGS based prodrugs, nitric oxide donor and polymers, and unmodified TPGs based formulations are discussed, focused on enhancing delivery efficiency as well as the therapeutic effect of agents.
Abstract: D-ɑ-tocopheryl polyethylene glycol succinate (Vitamin E TPGS or TPGS) has been approved by FDA as a safe adjuvant and widely used in drug delivery systems. The biological and physicochemical properties of TPGS provide multiple advantages for its applications in drug delivery like high biocompatibility, enhancement of drug solubility, improvement of drug permeation and selective antitumor activity. Notably, TPGS can inhibit the activity of ATP dependent P-glycoprotein and act as a potent excipient for overcoming multi-drug resistance (MDR) in tumor. In this review, we aim to discuss the recent advances of TPGS in drug delivery including TPGS based prodrugs, nitric oxide donor and polymers, and unmodified TPGS based formulations. These potential applications are focused on enhancing delivery efficiency as well as the therapeutic effect of agents, especially on overcoming MDR of tumors. It also demonstrates that the clinical translation of TPGS based nanomedicines is still faced with many challenges, which requires more detailed study on TPGS properties and based delivery system in the future.

262 citations

Journal ArticleDOI
D. Giron1
TL;DR: The current use of thermal analysis and combined techniques in research and development and in production is reviewed and the advantage of commercially coupled techniques to thermogravimetry is emphasized with some examples.
Abstract: Thermal analysis methods are well-established techniques in research laboratories of pharmaceutical industry. The robustness and sensitivity of instrumentation, the introduction of automation and of reliable software according to the industrial needs widened considerably the areas of applications inthe last decade. Calibration of instruments and validation of results follow the state of the art of cGMP as for other analytical techniques. Thermal analysis techniques are especially useful for the study of the behavior of the poly-phasic systems drug substances and excipients and find a unique place for new delivery systems. Since change of temperature and moisture occur by processing and storage, changes of the solid state may have a considerable effect on activity, toxicity and stability of compounds. Current requirements of the International Conference of Harmonisation for the characterization and the quantitation of polymorphism in new entities re-enforce the position of thermal analysis techniques. This challenging task needs the use of complementary methods. Combined techniques and microcalorimetry demonstrate their advantages. This article reviews the current use of thermal analysis and combined techniques in research and development and in production. The advantage of commercially coupled techniques to thermogravimetry is emphasized with some examples.

241 citations

Journal ArticleDOI
TL;DR: This review aims to highlight the development of novel vitamin E conjugates for the vectorization of active pharmaceutical ingredients through nanotechnologies, and describes the biology and the metabolic functions of vitamin E.

211 citations