scholarly journals Lipid Systems for the Delivery of Amphotericin B in Antifungal Therapy

Pharmaceutics ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 29 ◽  
Author(s):  
Faustino ◽  
Pinheiro
Keyword(s):  
Side Effects ◽  
Amphotericin B ◽  
Targeted Delivery ◽  
Oral Delivery ◽  
Water Solubility ◽  
Therapeutic Potential ◽  
Fungal Infections ◽  
Cost Effective ◽  
Oral Formulation ◽  
Life Threatening

Amphotericin B (AmB), a broad-spectrum polyene antibiotic in the clinic for more than fifty years, remains the gold standard in the treatment of life-threatening invasive fungal infections and visceral leishmaniasis. Due to its poor water solubility and membrane permeability, AmB is conventionally formulated with deoxycholate as a micellar suspension for intravenous administration, but severe infusion-related side effects and nephrotoxicity hamper its therapeutic potential. Lipid-based formulations, such as liposomal AmB, have been developed which significantly reduce the toxic side effects of the drug. However, their high cost and the need for parenteral administration limit their widespread use. Therefore, delivery systems that can retain or even enhance antimicrobial efficacy while simultaneously reducing AmB adverse events are an active area of research. Among those, lipid systems have been extensively investigated due to the high affinity of AmB for binding lipids. The development of a safe and cost-effective oral formulation able to improve drug accessibility would be a major breakthrough, and several lipid systems for the oral delivery of AmB are currently under development. This review summarizes recent advances in lipid-based systems for targeted delivery of AmB focusing on non-parenteral nanoparticulate formulations mainly investigated over the last five years and highlighting those that are currently in clinical trials.

Development of an Oral Amphotericin B Formulation as an Alternative Approach to Parenteral Amphotericin B Administration in the Treatment of Blood-Borne Fungal Infections

2020 ◽  
Vol 26 (14) ◽  
pp. 1521-1523 ◽  
Author(s):  
Kishor M. Wasan
Keyword(s):  
Side Effects ◽  
Amphotericin B ◽  
Organ Transplantation ◽  
Fungal Infections ◽  
Chemical Properties ◽  
Cost Effective ◽  
Oral Formulation ◽  
Vancouver General Hospital ◽  
Alternative Approach ◽  
Pre Treatment

: In the Fall of 1999, we presented at medical “Grand Rounds” to a number of Infectious Diseases physicians at Vancouver General Hospital about the co-administration of several antifungal compounds in the treatment of blood-borne fungal infections to patients who were immunocompromised (i.e. cancer patients, patients waiting organ transplantation, HIV/AIDs patients, etc.). During the presentation, a physician from the back of the room called out “can you develop an oral formulation of amphotericin B which could be effective and not have the side-effects associated with the parenteral formulations of the drug”. The physician stated that an oral formulation would be a big step forward, improving patient compliance, helping in pre-treatment without admitting patients to the hospital prior to organ transplantation and it would be cost-effective. Initially, I responded to the physician, that it would not be possible to develop an oral amphotericin B formulation that could be absorbed from the gastrointestinal (GI) tract in a high enough concentration to be effective in treating blood-borne fungal infections and yet remains non-toxic due to the physical chemical properties of the drug. However, as I travelled back to my lab from the meeting, it struck me that our understanding of how lipids had been processed and orally absorbed from the GI had advanced to the point the maybe incorporating amphotericin B into such lipids might work. Within several years, our laboratory was able to develop a novel oral amphotericin B formulation that was indeed effective in treating systemic fungal infections without the side-effects associated with the drug in a variety of fungal animal models.

scholarly journals In Vitro Evaluation of Self-Nano-Emulsifying Drug Delivery Systems (SNEDDS) Containing Room Temperature Ionic Liquids (RTILs) for the Oral Delivery of Amphotericin B

Pharmaceutics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 699 ◽  
Author(s):  
Eleni Kontogiannidou ◽  
Thomas Meikopoulos ◽  
Helen Gika ◽  
Emmanuel Panteris ◽  
Ioannis S. Vizirianakis ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Ionic Liquids ◽  
Amphotericin B ◽  
Oral Bioavailability ◽  
Oral Delivery ◽  
Room Temperature ◽  
Fungal Infections ◽  
Oral Formulation ◽  
Room Temperature Ionic Liquids

Amphotericin B (AmpB), one of the most commonly used agents in the treatment of severe fungal infections and life-threatening parasitic diseases such as visceral Leishmaniasis, has a negligible oral bioavailability, primarily due to a low solubility and permeability. To develop an oral formulation, medium chain triglycerides and nonionic surfactants in a self-nano-emulsifying drug delivery system (SNEDDS) containing AmpB were combined with room temperature ionic liquids (RTILs) of imidazolium. The presence of ionic liquids significantly enhanced the solubility of AmpB, exhibited a low toxicity and increased the transport of AmpB across Caco-2 cell monolayers. The combination of RTILs with a lipid formulation might be a promising strategy to improve the oral bioavailability of AmpB.

scholarly journals Black and white teas as potential agents to combine with amphotericin B and protect red blood cells from amphotericin B-mediated toxicity

2018 ◽  
Vol 78 (4) ◽  
pp. 673-678 ◽  
Author(s):  
V. M. Oliveira ◽  
N. M. Khalil ◽  
E. Carraro
Keyword(s):  
Side Effects ◽  
Red Blood Cells ◽  
Amphotericin B ◽  
Blood Cells ◽  
Fungal Infections ◽  
Black Tea ◽  
Additive Effects ◽  
Antifungal Effect ◽  
Black And White ◽  
Fungicidal Substance

Abstract Amphotericin B is a fungicidal substance that is treatment of choice for most systemic fungal infections affecting immunocompromised patients. However, severe side effects have limited the utility of this drug. The aim of this study was to evaluate the antifungal effect of the combination of amphotericin B with black tea or white tea and protective of citotoxic effect. The present study shows that white and black teas have additive effects with amphotericin B against some species Candida. In addition, the combination of white and black tea with amphotericin B may reduce the toxicity of amphotericin B to red blood cells. Our results suggest that white and black tea is a potential agent to combine with amphotericin for antifungal efficacy and to reduce the amphotericin dose to lessen side effects.

scholarly journals Preclinical Evaluation of UDCA-Containing Oral Formulation in Mice for the Treatment of Wet Age-Related Macular Degeneration

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 561 ◽  
Author(s):  
Maharjan ◽  
Kim ◽  
Jin ◽  
Ko ◽  
Song ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Oral Delivery ◽  
Water Solubility ◽  
Vision Loss ◽  
Oral Absorption ◽  
Aqueous Solubility ◽  
Oral Formulation ◽  
Preclinical Study ◽  
Age Related Macular Degeneration ◽  
Age Related

As a posterior ocular disease, wet age-related macular degeneration (WAMD) has been known to be related to vision loss, accompanying ocular complications. The intravitreous injection of VEGF antibodies has been reported to be an effective treatment to relieve symptoms of WAMD. However, the limitations of this treatment are high costs and invasiveness. For this reason, oral delivery route can be considered as a cost-effective way and the safest method to deliver drug molecules to the eyes. Accordingly, ursodeoxycholic acid (UDCA) was included in the oral formulation as the potential substance for the cure of WAMD in the animal model. Various pharmacological activities, such as antioxidant or anti-inflammatory effects, have been reported for UDCA and recent reports support the effects of UDCA in ocular treatment. However, due to poor water solubility and low pKa (around 5.0), it has been challenging to formulate aqueous solution of UDCA in the neutral pH range. In the present study, we confirmed the aqueous solubility of the oral UDCA formulation and performed a preclinical study, including pharmacokinetic profiling and WAMD model efficacy study in mice after oral administration of the drug solution. The results demonstrated that the formulation improved bioavailability of UDCA and efficiently delivered UDCA to the eye tissues after oral absorption. UDCA formulation was found to have inhibitory effects of choroidal neovascularization with a functional recovery in mice retinas. Taken together, our results suggest that the oral UDCA formulation could be used as a potent supplement for the cure of WAMD and related retinal diseases.

scholarly journals Formulation of Liver-Specific PLGA-DY-635 Nanoparticles Loaded with the Protein Kinase C Inhibitor Bisindolylmaleimide I

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1110
Author(s):  
Blerina Shkodra ◽  
Adrian T. Press ◽  
Antje Vollrath ◽  
Ivo Nischang ◽  
Stephanie Schubert ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Targeted Delivery ◽  
Near Infrared ◽  
Water Solubility ◽  
Analytical Ultracentrifugation ◽  
Therapeutic Potential ◽  
Kinase C ◽  
Protein Kinase C Inhibitor

Bisindolylmaleimide I (BIM-I) is a competitive pan protein kinase C inhibitor with anti-inflammatory and anti-metastatic properties, suggested to treat inflammatory diseases and various cancer entities. However, despite its therapeutic potential, BIM-I has two major drawbacks, i.e., it has a poor water solubility, and it binds the human ether-à-go-go-related gene (hERG) ion channels, potentially causing deadly arrhythmias. In this case, a targeted delivery of BIM-I is imperative to minimize peripheral side effects. To circumvent these drawbacks BIM-I was encapsulated into nanoparticles prepared from poly(lactic-co-glycolic acid) (PLGA) functionalized by the near-infrared dye DY-635. DY-635 served as an active targeting moiety since it selectively binds the OATP1B1 and OATP1B3 transporters that are highly expressed in liver and cancer cells. PLGA-DY-635 (BIM-I) nanoparticles were produced by nanoprecipitation and characterized using dynamic light scattering, analytical ultracentrifugation, and cryogenic transmission electron microscopy. Particle sizes were found to be in the range of 20 to 70 nm, while a difference in sizes between the drug-loaded and unloaded particles was observed by all analytical techniques. In vitro studies demonstrated that PLGA-DY-635 (BIM-I) NPs prevent the PKC activation efficiently, proving the efficacy of the inhibitor after its encapsulation, and suggesting that BIM-I is released from the PLGA-NPs. Ultimately, our results present a feasible formulation strategy that improved the cytotoxicity profile of BIM-I and showed a high cellular uptake in the liver as demonstrated in vivo by intravital microscopy investigations.

scholarly journals Curcumin micelles entrapped in eudragit S-100 matrix: a synergistic strategy for enhanced oral delivery

2021 ◽  
pp. FSO677
Author(s):  
Helmy Yusuf ◽  
Rizka Arifa Rahmawati ◽  
M Agus Syamsur Rijal ◽  
Dewi Isadiartuti
Keyword(s):  
Oral Delivery ◽  
Water Solubility ◽  
Amorphous State ◽  
Amorphous Solid ◽  
Oral Formulation ◽  
Poloxamer 407 ◽  
Dispersion Matrix ◽  
Gi Tract ◽  
S 100 ◽  
High Fraction

Background: Therapeutic activities of curcumin (CUR) via oral administration are hampered by the lack of bioavailability due to its poor water solubility and rapid degradation in GI tract. Materials & methods: This preliminary study developed CUR micelle-eudragit S100 (EUD) dry powder (CM-EDP) spray-dried formulations. Poloxamer 407 was used as a micelle-forming agent and EUD as an entrapping matrix for protection over hydrolysis and enzymes in the GI tract. Results: The morphology of CM-EDP showed agglomeration with cratering on the surface of particles. Differential thermal analysis and x-ray diffractometry data exhibited evidence that CUR was converted into amorphous solid. An increased concentration of micelle-forming and dispersion matrix polymers resulted in a high fraction of drug being converted into the amorphous state. A significant increase in dissolution by 7–10 times was achieved compared with that of raw CUR. Conclusion: The present study disclosed the CM-EDP potency for future development of CUR oral formulation.

scholarly journals Biomarker-guided antifungal stewardship policies for patients with invasive candidiasis

2019 ◽  
Author(s):  
Behnam Honarvar ◽  
Kamran Bagheri Lankarani ◽  
Mehdi Taghavi ◽  
Ghasem Vahedi ◽  
Esmaeil Mortaz
Keyword(s):  
Early Diagnosis ◽  
Invasive Candidiasis ◽  
Fungal Infections ◽  
National Health System ◽  
Cost Effective ◽  
Diagnostic Methods ◽  
Antifungal Stewardship ◽  
National Healthcare ◽  
Life Threatening ◽  
Effective Use

Invasive fungal infections (IFIs) are among the life-threatening issues in patients with impaired immune system. High administration of antifungals in these patients imposes a heavy economic burden on the national health system. In addition, despite the usually expensive antifungal regimens, the mortality rate due to fungal infections is still high, resulting in the loss of hundreds of lives per year.Survival rate is an indicator of the success of national healthcare policies. Early diagnosis of IFI is critical because any delays may be fatal. The weakness of the old-fashioned culture-based diagnostic methods lies in their time-consuming laboratory procedures. To overcome this problem, several diagnostic approaches have been developed to facilitate the early diagnosis of invasive candidiasis as the most prevalent IFI.These methods are based on the detection of serologic and molecular footprints. However, nowadays, antibiotic resistance and proper and cost-effective use of antibiotics are given special attention in national healthcare policies. The instructions for controlling these indices have been collected under the name of antibiotic stewardship. The present review study was targeted toward providing insight into novel diagnostic biomarkers and antifungal stewardship programs. The simultaneous investigation of these two issues facilitates the achievement of a novel health policy for the treatment of systemic candidiasis in immunocompromised patients.

Colloidal Nanocarriers as Versatile Targeted Delivery Systems for Cervical Cancer

2020 ◽  
Vol 26 (40) ◽  
pp. 5174-5187 ◽  
Author(s):  
Abimanyu Sugumaran ◽  
Vishali Mathialagan
Keyword(s):  
Cervical Cancer ◽  
Side Effects ◽  
Anticancer Agents ◽  
Targeted Delivery ◽  
Metallic Nanoparticles ◽  
Polymeric Nanoparticles ◽  
Survival Rates ◽  
Cost Effective ◽  
Current Treatment ◽  
Normal Tissues

Background: The second most common malignant cancer of the uterus is cervical cancer, which is present worldwide, has a rising death rate and is predominant in developing countries. Different classes of anticancer agents are used to treat cervical carcinoma. The use of these agents results in severe untoward side-effects, toxicity, and multidrug resistance (MDR) with higher chances of recurrence and spread beyond the pelvic region. Moreover, the resulting clinical outcome remains very poor even after surgical procedures and treatment with conventional chemotherapy. Because of the nonspecificity of their use, the agents wipe out both cancerous and normal tissues. Colloidal nano dispersions have now been focusing on site-specific delivery for cervical cancer, and there has been much advancement. Methods: This review aims to highlight the problems in the current treatment of cervical cancer and explore the potential of colloidal nanocarriers for selective delivery of anticancer drugs using available literature. Results: In this study, we surveyed the role and potential of different colloidal nanocarriers in cervical cancer, such as nanoemulsion, nanodispersions, polymeric nanoparticles, and metallic nanoparticles and photothermal and photodynamic therapy. We found significant advancement in colloidal nanocarrier-based cervical cancer treatment. Conclusion: Cervical cancer-targeted treatment with colloidal nanocarriers would hopefully result in minimal toxic side effects, reduced dosage frequency, and lower MDR incidence and enhance the patient survival rates. The future direction of the study should be focused more on the regulatory barrier of nanocarriers based on clinical outcomes for cervical cancer targeting with cost-effective analysis.

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