A review on liposomal amphotericin b in antifungal therapy

To reduce the in-vivo toxicity of the broad-spectrum antifungal drug amphotericin B, various lipid formulations of amphotericin B, ranging from lipid complexes to small unilamellar liposomes, have been developed and subsequently commercialized. These structurally diverse formulations differ in their serum pharmacokinetics as well as their tissue localization, tissue retention, and toxicity. This difference can affect the choice of formulation for a given infection, the time of initiation of treatment, and the dosing regimen. Although preclinical studies have shown similarities in the in-vitro and in-vivo antifungal activity of the formulations with comparable dosing, their acute, and chronic toxicity. Profiles are not the same, and this has a significant impact on their therapeutic indices, especially in high-risk, immunosuppressed patients. With the recent introduction of new antifungal drugs to treat the increasing numbers of infected patients, the amphotericin B lipid formulations are now being studied to evaluate their potential in combinational drug regimens. With proven efficacy demonstrated during the past decade, it is expected that amphotericin B lipid formulations will remain an important part of antifungal drug therapy.

A 3D-Printed Polymer–Lipid-Hybrid Tablet towards the Development of Bespoke SMEDDS Formulations

3D printing is a rapidly growing area of interest within pharmaceutical science thanks to its versatility in creating different dose form geometries and drug doses to enable the personalisation of medicines. Research in this area has been dominated by polymer-based materials; however, for poorly water-soluble lipophilic drugs, lipid formulations present advantages in improving bioavailability. This study progresses the area of 3D-printed solid lipid formulations by providing a 3D-printed dissolvable polymer scaffold to compartmentalise solid lipid formulations within a single dosage form. This allows the versatility of different drugs in different lipid formulations, loaded into different compartments to generate wide versatility in drug release, and specific control over release geometry to tune release rates. Application to a range of drug molecules was demonstrated by incorporating the model lipophilic drugs; halofantrine, lumefantrine and clofazimine into the multicompartmental scaffolded tablets. Fenofibrate was used as the model drug in the single compartment scaffolded tablets for comparison with previous studies. The formulation-laden scaffolds were characterised using X-ray CT and dispersion of the formulation was studied using nephelometry, while release of a range of poorly water-soluble drugs into different gastrointestinal media was studied using HPLC. The studies show that dispersion and drug release are predictably dependent on the exposed surface area-to-volume ratio (SA:V) and independent of the drug. At the extremes of SA:V studied here, within 20 min of dissolution time, formulations with an SA:V of 0.8 had dispersed to between 90 and 110%, and completely released the drug, where as an SA:V of 0 yielded 0% dispersion and drug release. Therefore, this study presents opportunities to develop new dose forms with advantages in a polypharmacy context.

Mucormycosis: the black fungus maiming COVID-19 patients in India

The COVID-19 infection caused by the novel SARS-CoV-2 may be associated with a wide range of disease patterns, ranging from mild to life-threatening pneumonia. Mucormycosis is an emerging angioinvasive fungal infection caused by the ubiquitous filamentous fungi of the Mucorales order of the class of Zygomycetes. The prevalence of mucormycosis in India is about 80 times the prevalence in developed countries. Mucorales invade deep tissues via inhalation of airborne spores, percutaneous inoculation or ingestion. Rhino-orbito-cerebral form of mucormycosis is a relatively fatal infection and mortality rate rises to 50-85%. Extensive use of corticosteroids/monoclonal antibodies/broad-spectrum antibiotics may lead to the development/exacerbation of a preexisting fungal disease. Only amphotericin B and its lipid formulations and recently isavuconazole have been studied as first-line therapy for mucormycosis. On the contrary, posaconazole has been mainly studied as salvage therapy.

Nanocarriers for Biomedicine: From Lipid Formulations to Inorganic and Hybrid Nanoparticles

Encapsulation of cargoes in nanocontainers is widely used in different fields to solve the problems of their solubility, homogeneity, stability, protection from unwanted chemical and biological destructive effects, and functional activity improvement. This approach is of special importance in biomedicine, since this makes it possible to reduce the limitations of drug delivery related to the toxicity and side effects of therapeutics, their low bioavailability and biocompatibility. This review highlights current progress in the use of lipid systems to deliver active substances to the human body. Various lipid compositions modified with amphiphilic open-chain and macrocyclic compounds, peptide molecules and alternative target ligands are discussed. Liposome modification also evolves by creating new hybrid structures consisting of organic and inorganic parts. Such nanohybrid platforms include cerasomes, which are considered as alternative nanocarriers allowing to reduce inherent limitations of lipid nanoparticles. Compositions based on mesoporous silica are beginning to acquire no less relevance due to their unique features, such as advanced porous properties, well-proven drug delivery efficiency and their versatility for creating highly efficient nanomaterials. The types of silica nanoparticles, their efficacy in biomedical applications and hybrid inorganic-polymer platforms are the subject of discussion in this review, with current challenges emphasized.

Nanotechnology approaches for delivery and targeting of Amphotericin B in fungal and parasitic diseases

Amphotericin B (AMB), with widespread antifungal and anti-parasitic activities and low cross-resistance with other drugs, has long been identified as a potent antimicrobial drug. However, its clinical toxicities, especially nephrotoxicity, have limited its use in clinical practice. Lately, nano-based systems have been the subject of serious research and becoming an effective strategy to improve toxicity and antimicrobial potency. Commercial AMB lipid formulations have been developed in order to improve the therapeutic index and nephrotoxicity, while limited use is mainly due to their high cost. The review aimed to highlight the updated information on nanotechnology-based approaches to the development of AMB delivery and targeting systems for treatment of fungal diseases and leishmaniasis, regarding therapeutic challenges and achievements of various delivery systems.

Lipid Formulations and Bioconjugation Strategies for Indomethacin Therapeutic Advances

Indomethacin (IND) is a drug which after successful clinical trials became available for general prescription in 1965 and from that time is one of the most widely used anti-inflammatory drug with the highest potencies in the in vitro and in vivo models. However, despite its high therapeutic efficacy in relieving the symptoms of certain arthritis and in treating gout or collagen diseases, administration of IND causes a number of adverse effects, such as gastrointestinal ulceration, frequent central nervous system disorders and renal toxicity. These obstacles significantly limit the practical applications of IND and make that 10–20% of patients discontinue its use. Therefore, during the last three decades many attempts have been made to design novel formulations of IND aimed to increase its therapeutic benefits minimizing its adverse effects. In this review we summarize pharmacological information about IND and analyze its new lipid formulations and lipid bioconjugates as well as discuss their efficacy and potential application.