Nanotechnological approaches for pentamidine delivery

Andreana, Ilaria; Bincoletto, Valeria; Milla, Paola; Dosio, Franco; Stella, Barbara; Arpicco, Silvia Maria

doi:10.1007/s13346-022-01127-4

Cited by 11 publications

(6 citation statements)

References 135 publications

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“…However, some nebulized drug may not reach the deeper airways, since a small portion of larger droplets can be produced by the nebulizer, which will interact with the upper part of the respiratory tree where are mainly located the parasites responsible for MCL, the most difficult form of the disease to treat [9]. The nebulization of pentamidine-loaded liposomes is an undemanding methodology and a patient-friendly strategy for the treatment of leishmaniasis, and it is less aggressive than intravenous, intramuscular or subcutaneous administration [84]. The pulmonary delivery of pentamidine can target the drug to Leishmania parasites via uptake by the macrophages, reducing toxic systemic effects and limiting the emergence of resistance in the pathogen.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Evaluation of Aerosol Therapy with Pentamidine-Loaded Liposomes Coated with Chondroitin Sulfate or Heparin for the Treatment of Leishmaniasis

et al. 2023

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The second-line antileishmanial compound pentamidine is administered intramuscularly or, preferably, by intravenous infusion, with its use limited by severe adverse effects, including diabetes, severe hypoglycemia, myocarditis and renal toxicity. We sought to test the potential of phospholipid vesicles to improve the patient compliance and efficacy of this drug for the treatment of leishmaniasis by means of aerosol therapy. The targeting to macrophages of pentamidine-loaded liposomes coated with chondroitin sulfate or heparin increased about twofold (up to ca. 90%) relative to noncoated liposomes. The encapsulation of pentamidine in liposomes ameliorated its activity on the amastigote and promastigote forms of Leishmania infantum and Leishmania pifanoi, and it significantly reduced cytotoxicity on human umbilical endothelial cells, for which the concentration inhibiting 50% of cell viability was 144.2 ± 12.7 µM for pentamidine-containing heparin-coated liposomes vs. 59.3 ± 4.9 µM for free pentamidine. The deposition of liposome dispersions after nebulization was evaluated with the Next Generation Impactor, which mimics human airways. Approximately 53% of total initial pentamidine in solution reached the deeper stages of the impactor, with a median aerodynamic diameter of ~2.8 µm, supporting a partial deposition on the lung alveoli. Upon loading pentamidine in phospholipid vesicles, its deposition in the deeper stages significantly increased up to ~68%, and the median aerodynamic diameter decreased to a range between 1.4 and 1.8 µm, suggesting a better aptitude to reach the deeper lung airways in higher amounts. In all, nebulization of liposome-encapsulated pentamidine improved the bioavailability of this neglected drug by a patient-friendly delivery route amenable to self-administration, paving the way for the treatment of leishmaniasis and other infections where pentamidine is active.

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Section: Discussionmentioning

confidence: 99%

In Vitro Evaluation of Aerosol Therapy with Pentamidine-Loaded Liposomes Coated with Chondroitin Sulfate or Heparin for the Treatment of Leishmaniasis

et al. 2023

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“…The downside of this review is that it does not address the toxicity issues surrounding the administration of free-form diarylamidines; although, in retrospect, this was addressed more than a decade ago [ 87 ] with the advent of micro- (slow-release liposomal formulations and thermo hydrogel preparations), and nano-encapsulation-targeted therapies [ 167 , 168 ].…”

Section: Discussionmentioning

confidence: 99%

COVID-19 and Diarylamidines: The Parasitic Connection

Hulme

2023

IJMS

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As emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants (Omicron) continue to outpace and negate combinatorial vaccines and monoclonal antibody therapies targeting the spike protein (S) receptor binding domain (RBD), the appetite for developing similar COVID-19 treatments has significantly diminished, with the attention of the scientific community switching to long COVID treatments. However, treatments that reduce the risk of “post-COVID-19 syndrome” and associated sequelae remain in their infancy, particularly as no established criteria for diagnosis currently exist. Thus, alternative therapies that reduce infection and prevent the broad range of symptoms associated with ‘post-COVID-19 syndrome’ require investigation. This review begins with an overview of the parasitic–diarylamidine connection, followed by the renin-angiotensin system (RAS) and associated angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSSR2) involved in SARS-CoV-2 infection. Subsequently, the ability of diarylamidines to inhibit S-protein binding and various membrane serine proteases associated with SARS-CoV-2 and parasitic infections are discussed. Finally, the roles of diarylamidines (primarily DIZE) in vaccine efficacy, epigenetics, and the potential amelioration of long COVID sequelae are highlighted.

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“…Therefore, a deeper analysis of the in vivo behavior of the PTM-loaded nanocarrier is required. Particularly using suitable animal models for which PTM has been repurposed [ 102 , 103 ].…”

Section: Future Perspectivesmentioning

confidence: 99%

Nanomedicine for Treating Muscle Dystrophies: Opportunities, Challenges, and Future Perspectives

Ahmed

Qaisar

2022

IJMS

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Muscular dystrophies are a group of genetic muscular diseases characterized by impaired muscle regeneration, which leads to pathological inflammation that drives muscle wasting and eventually results in weakness, functional dependency, and premature death. The most known causes of death include respiratory muscle failure due to diaphragm muscle decay. There is no definitive treatment for muscular dystrophies, and conventional therapies aim to ameliorate muscle wasting by promoting physiological muscle regeneration and growth. However, their effects on muscle function remain limited, illustrating the requirement for major advancements in novel approaches to treatments, such as nanomedicine. Nanomedicine is a rapidly evolving field that seeks to optimize drug delivery to target tissues by merging pharmaceutical and biomedical sciences. However, the therapeutic potential of nanomedicine in muscular dystrophies is poorly understood. This review highlights recent work in the application of nanomedicine in treating muscular dystrophies. First, we discuss the history and applications of nanomedicine from a broader perspective. Second, we address the use of nanoparticles for drug delivery, gene regulation, and editing to target Duchenne muscular dystrophy and myotonic dystrophy. Next, we highlight the potential hindrances and limitations of using nanomedicine in the context of cell culture and animal models. Finally, the future perspectives for using nanomedicine in clinics are summarized with relevance to muscular dystrophies.

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Nanotechnological approaches for pentamidine delivery

Cited by 11 publications

References 135 publications

In Vitro Evaluation of Aerosol Therapy with Pentamidine-Loaded Liposomes Coated with Chondroitin Sulfate or Heparin for the Treatment of Leishmaniasis

In Vitro Evaluation of Aerosol Therapy with Pentamidine-Loaded Liposomes Coated with Chondroitin Sulfate or Heparin for the Treatment of Leishmaniasis

COVID-19 and Diarylamidines: The Parasitic Connection

Nanomedicine for Treating Muscle Dystrophies: Opportunities, Challenges, and Future Perspectives

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