Drug Delivery for Anti-Infective Agents

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Biopharmaceutics".

Deadline for manuscript submissions: closed (20 January 2021) | Viewed by 68730

Special Issue Editor


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Guest Editor
Department of Pharmaceutical Technology and Chemistry, Tropical Health Institute, University of Navarra, 31008 Pamplona, Spain
Interests: delivery strategies for the prevention and treatment of leishmaniasis with special focus in non-parenteral (oral or topical) administration routes for the chemo-and immunotherapy of cutaneous leishmaniasis

Special Issue Information

Dear Colleagues,

The high prevalence of infective diseases, antimicrobial resistance and biofilm-associated infections on implantable devices have fueled the research for new and more effective treatments. New delivery strategies/materials/vehicles perform a promising platform for addressing this challenge. Meanwhile the discovering of new drugs is falling behind. Such vehicles can increase drug bioavailability and site-specific delivery, optimizing therapeutic index and dose-effect relationship. It would decrease the treatment duration and thus, the chance to acquire drug resistance.

The main objective of this special issue is to provide a review on the potential of such materials and vehicles in the treatment of infections. The vehicles can exhibit intrinsic antimicrobial properties (i.e. metallic particles) or serve as a cargo for delivering the anti-infective agents alone or in combination. They can facilitate the access of drugs to hard-to-reach locations such as intracellular pathogens, granulomas (i.e. tuberculosis) or deep dermal infections (i.e. leishmaniasis). Nanomaterials can also provide a high coating surface for decorating medical devices and avoid biofilm-associated infections. Finally, PK/PD analysis of these delivery systems could optimize the posology of drugs while preserving their efficacy.

Dr. María Socorro Espuelas Millán
Guest Editor

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Keywords

  • anti-infective agents
  • micro- and nanoparticles (all materials)
  • antimicrobial resistance
  • biofilm
  • PK/PD
  • intracellular pathogens

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Published Papers (14 papers)

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Research

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14 pages, 1676 KiB  
Article
Film-Forming Systems for the Delivery of DNDI-0690 to Treat Cutaneous Leishmaniasis
by Katrien Van Bocxlaer, Kerri-Nicola McArthur, Andy Harris, Mo Alavijeh, Stéphanie Braillard, Charles E. Mowbray and Simon L. Croft
Pharmaceutics 2021, 13(4), 516; https://doi.org/10.3390/pharmaceutics13040516 - 8 Apr 2021
Cited by 12 | Viewed by 3173
Abstract
In cutaneous leishmaniasis (CL), parasites reside in the dermis, creating an opportunity for local drug administration potentially reducing adverse effects and improving treatment adherence compared to current therapies. Polymeric film-forming systems (FFSs) are directly applied to the skin and form a thin film [...] Read more.
In cutaneous leishmaniasis (CL), parasites reside in the dermis, creating an opportunity for local drug administration potentially reducing adverse effects and improving treatment adherence compared to current therapies. Polymeric film-forming systems (FFSs) are directly applied to the skin and form a thin film as the solvent evaporates. In contrast to conventional topical dosage forms, FFSs strongly adhere to the skin, favouring sustained drug delivery to the affected site, reducing the need for frequent applications, and enhancing patient compliance. This study reports the first investigation of the use of film-forming systems for the delivery of DNDI-0690, a nitroimidazole compound with potent activity against CL-causing Leishmania species. A total of seven polymers with or without plasticiser were evaluated for drying time, stickiness, film-flexibility, and cosmetic attributes; three FFSs yielded a positive evaluation for all test parameters. The impact of each of these FFSs on the permeation of the model skin permeant hydrocortisone (hydrocortisone, 1% (w/v) across the Strat-M membrane was evaluated, and the formulations resulting in the highest and lowest permeation flux (Klucel LF with triethyl citrate and Eudragit RS with dibutyl sebacate, respectively) were selected as the FFS vehicle for DNDI-0690. The release and skin distribution of the drug upon application to Leishmania-infected and uninfected BALB/c mouse skin were examined using Franz diffusion cells followed by an evaluation of the efficacy of both DNDI-0690 FFSs (1% (w/v)) in an experimental CL model. Whereas the Eudragit film resulted in a higher permeation of DNDI-0690, the Klucel film was able to deposit four times more drug into the skin, where the parasite resides. Of the FFSs formulations, only the Eudragit system resulted in a reduced parasite load, but not reduced lesion size, when compared to the vehicle only control. Whereas drug delivery into the skin was successfully modulated using different FFS systems, the FFS systems selected were not effective for the topical application of DNDI-0690. The convenience and aesthetic of FFS systems alongside their ability to modulate drug delivery to and into the skin merit further investigation using other promising antileishmanial drugs. Full article
(This article belongs to the Special Issue Drug Delivery for Anti-Infective Agents)
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25 pages, 29886 KiB  
Article
Liposomes as a Nanoplatform to Improve the Delivery of Antibiotics into Staphylococcus aureus Biofilms
by Magda Ferreira, Sandra N. Pinto, Frederico Aires-da-Silva, Ana Bettencourt, Sandra I. Aguiar and Maria Manuela Gaspar
Pharmaceutics 2021, 13(3), 321; https://doi.org/10.3390/pharmaceutics13030321 - 2 Mar 2021
Cited by 33 | Viewed by 4375
Abstract
Staphylococcus aureus biofilm-associated infections are a major public health concern. Current therapies are hampered by reduced penetration of antibiotics through biofilm and low accumulation levels at infected sites, requiring prolonged usage. To overcome these, repurposing antibiotics in combination with nanotechnological platforms is one [...] Read more.
Staphylococcus aureus biofilm-associated infections are a major public health concern. Current therapies are hampered by reduced penetration of antibiotics through biofilm and low accumulation levels at infected sites, requiring prolonged usage. To overcome these, repurposing antibiotics in combination with nanotechnological platforms is one of the most appealing fast-track and cost-effective approaches. In the present work, we assessed the potential therapeutic benefit of three antibiotics, vancomycin, levofloxacin and rifabutin (RFB), through their incorporation in liposomes. Free RFB displayed the utmost antibacterial effect with MIC and MBIC50 below 0.006 µg/mL towards a methicillin susceptible S. aureus (MSSA). RFB was selected for further in vitro studies and the influence of different lipid compositions on bacterial biofilm interactions was evaluated. Although positively charged RFB liposomes displayed the highest interaction with MSSA biofilms, RFB incorporated in negatively charged liposomes displayed lower MBIC50 values in comparison to the antibiotic in the free form. Preliminary safety assessment on all RFB formulations towards osteoblast and fibroblast cell lines demonstrated that a reduction on cell viability was only observed for the positively charged liposomes. Overall, negatively charged RFB liposomes are a promising approach against biofilm S. aureus infections and further in vivo studies should be performed. Full article
(This article belongs to the Special Issue Drug Delivery for Anti-Infective Agents)
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24 pages, 14063 KiB  
Article
Solid Lipid Nanoparticles as Formulative Strategy to Increase Oral Permeation of a Molecule Active in Multidrug-Resistant Tuberculosis Management
by Antonella Obinu, Elena Piera Porcu, Sandra Piras, Roberta Ibba, Antonio Carta, Paola Molicotti, Rossana Migheli, Alessandro Dalpiaz, Luca Ferraro, Giovanna Rassu, Elisabetta Gavini and Paolo Giunchedi
Pharmaceutics 2020, 12(12), 1132; https://doi.org/10.3390/pharmaceutics12121132 - 24 Nov 2020
Cited by 22 | Viewed by 3003
Abstract
The role of mycobacterial efflux pumps in drug-resistant tuberculosis has been widely reported. Recently, a new compound, named SS13, has been synthesized, and its activity as a potential efflux inhibitor has been demonstrated. In this work, the chemical–physical properties of the SS13 were [...] Read more.
The role of mycobacterial efflux pumps in drug-resistant tuberculosis has been widely reported. Recently, a new compound, named SS13, has been synthesized, and its activity as a potential efflux inhibitor has been demonstrated. In this work, the chemical–physical properties of the SS13 were investigated; furthermore, a formulative study aimed to develop a formulation suitable for oral administration was performed. SS13 shows nonintrinsic antitubercular activity, but it increases the antitubercular activity of all the tested drugs on several strains. SS13 is insoluble in different simulated gastrointestinal media; thus, its oral absorption could be limited. Solid lipid nanoparticles (SLNs) were, therefore, developed by using two different lipids, Witepsol and/or Gelucire. Nanoparticles, having a particle size (range of 200–450 nm with regards to the formulation composition) suitable for intestinal absorption, are able to load SS13 and to improve its permeation through the intestinal mucosa compared to the pure compound. The cytotoxicity is influenced by the concentration of nanoparticles administered. These promising results support the potential application of these nanocarriers for increasing the oral permeation of SS13 in multidrug-resistant tuberculosis management. Full article
(This article belongs to the Special Issue Drug Delivery for Anti-Infective Agents)
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18 pages, 1158 KiB  
Article
Berberine-Loaded Liposomes for the Treatment of Leishmania infantum-Infected BALB/c Mice
by Alba Calvo, Esther Moreno, Esther Larrea, Carmen Sanmartín, Juan Manuel Irache and Socorro Espuelas
Pharmaceutics 2020, 12(9), 858; https://doi.org/10.3390/pharmaceutics12090858 - 9 Sep 2020
Cited by 37 | Viewed by 3994
Abstract
Berberine (BER)—an anti-inflammatory quaternary isoquinoline alkaloid extracted from plants—has been reported to have a variety of biologic properties, including antileishmanial activity. This work addresses the preparation of BER-loaded liposomes with the aim to prevent its rapid liver metabolism and improve the drug selective [...] Read more.
Berberine (BER)—an anti-inflammatory quaternary isoquinoline alkaloid extracted from plants—has been reported to have a variety of biologic properties, including antileishmanial activity. This work addresses the preparation of BER-loaded liposomes with the aim to prevent its rapid liver metabolism and improve the drug selective delivery to the infected organs in visceral leishmaniasis (VL). BER liposomes (LP-BER) displayed a mean size of 120 nm, negative Z-potential of −38 mV and loaded 6 nmol/μmol lipid. In vitro, the loading of BER in liposomes enhanced its selectivity index more than 7-fold by decreasing its cytotoxicity to macrophages. In mice, LP-BER enhanced drug accumulation in the liver and the spleen. Consequently, the liposomal delivery of the drug reduced parasite burden in the liver and spleen by three and one logarithms (99.2 and 93.5%), whereas the free drug only decreased the infection in the liver by 1-log. The organ drug concentrations—far from IC50 values— indicate that BER immunomodulatory activity or drug metabolites also contribute to the efficacy. Although LP-BER decreased 10-fold—an extremely rapid clearance of the free drug in mice—the value remains very high. Moreover, LP-BER reduced plasma triglycerides levels. Full article
(This article belongs to the Special Issue Drug Delivery for Anti-Infective Agents)
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13 pages, 1780 KiB  
Article
Itaconic Acid Increases the Efficacy of Tobramycin against Pseudomonas aeruginosa Biofilms
by Duy-Khiet Ho, Chiara De Rossi, Brigitta Loretz, Xabier Murgia and Claus-Michael Lehr
Pharmaceutics 2020, 12(8), 691; https://doi.org/10.3390/pharmaceutics12080691 - 22 Jul 2020
Cited by 7 | Viewed by 3260
Abstract
The search for novel therapeutics against pulmonary infections, in particular Pseudomonas aeruginosa (PA) biofilm infections, has been intense to deal with the emergent rise of antimicrobial resistance. Despite the numerous achievements in drug discovery and delivery strategies, only a limited number of therapeutics [...] Read more.
The search for novel therapeutics against pulmonary infections, in particular Pseudomonas aeruginosa (PA) biofilm infections, has been intense to deal with the emergent rise of antimicrobial resistance. Despite the numerous achievements in drug discovery and delivery strategies, only a limited number of therapeutics reach the clinic. To allow a timely preclinical development, a formulation should be highly effective, safe, and most importantly facile to produce. Thus, a simple combination of known actives that enhances the therapeutic efficacy would be a preferential choice compared to advanced drug delivery systems. In this study, we propose a novel combination of an anti-inflammatory agent—itaconic acid (itaconate, IA)—and an approved antibiotic—tobramycin (Tob) or ciprofloxacin (Cipro). The combination of Tob and IA at a molar ratio of 1:5 increased the biofilm eradicating efficacy in the strain PA14 wild type (wt) by ~4-fold compared to Tob alone. In contrast, such effect was not observed for the combination of IA with Cipro. Subsequent studies on the influence of IA on bacterial growth, pyocyanin production, and Tob biofilm penetration indicated that complexation with IA enhanced the transport of Tob through the biofilm. We recommend the simple and effective combination of Tob:IA for further testing in advanced preclinical models of PA biofilm infections. Full article
(This article belongs to the Special Issue Drug Delivery for Anti-Infective Agents)
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17 pages, 4663 KiB  
Article
Comparison between Colistin Sulfate Dry Powder and Solution for Pulmonary Delivery
by Frédéric Tewes, Julien Brillault, Nicolas Gregoire, Jean-Christophe Olivier, Isabelle Lamarche, Christophe Adier, Anne-Marie Healy and Sandrine Marchand
Pharmaceutics 2020, 12(6), 557; https://doi.org/10.3390/pharmaceutics12060557 - 17 Jun 2020
Cited by 7 | Viewed by 4415
Abstract
To assess the difference in the fate of the antibiotic colistin (COLI) after its pulmonary delivery as a powder or a solution, we developed a COLI powder and evaluated the COLI pharmacokinetic properties in rats after pulmonary administration of the powder or the [...] Read more.
To assess the difference in the fate of the antibiotic colistin (COLI) after its pulmonary delivery as a powder or a solution, we developed a COLI powder and evaluated the COLI pharmacokinetic properties in rats after pulmonary administration of the powder or the solution. The amorphous COLI powder prepared by spray drying was characterized by a mass median aerodynamic diameter and fine particle fraction of 2.68 ± 0.07 µm and 59.5 ± 5.4%, respectively, when emitted from a Handihaler®. After intratracheal administration, the average pulmonary epithelial lining fluid (ELF): plasma area under the concentration versus time curves (AUC) ratios were 570 and 95 for the COLI solution and powder, respectively. However, the same COLI plasma concentration profiles were obtained with the two formulations. According to our pharmacokinetic model, this difference in ELF COLI concentration could be due to faster systemic absorption of COLI after the powder inhalation than for the solution. In addition, the COLI apparent permeability (Papp) across a Calu-3 epithelium model increased 10-fold when its concentration changed from 100 to 4000 mg/L. Based on this last result, we propose that the difference observed in vivo between the COLI solution and powder could be due to a high local ELF COLI concentration being obtained at the site where the dry particles impact the lung. This high local COLI concentration can lead to a local increase in COLI Papp, which is associated with a high concentration gradient and could produce a high local transfer of COLI across the epithelium and a consequent increase in the overall absorption rate of COLI. Full article
(This article belongs to the Special Issue Drug Delivery for Anti-Infective Agents)
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19 pages, 1891 KiB  
Article
Evaluation of Skin Permeation and Retention of Topical Dapsone in Murine Cutaneous Leishmaniasis Lesions
by Esther Moreno, Alba Calvo, Juana Schwartz, Iñigo Navarro-Blasco, Elena González-Peñas, Carmen Sanmartín, Juan Manuel Irache and Socorro Espuelas
Pharmaceutics 2019, 11(11), 607; https://doi.org/10.3390/pharmaceutics11110607 - 13 Nov 2019
Cited by 14 | Viewed by 3700
Abstract
The oral administration of dapsone (DAP) for the treatment of cutaneous leishmaniasis (CL) is effective, although serious hematological side effects limit its use. In this study, we evaluated this drug for the topical treatment of CL. As efficacy depends on potency and skin [...] Read more.
The oral administration of dapsone (DAP) for the treatment of cutaneous leishmaniasis (CL) is effective, although serious hematological side effects limit its use. In this study, we evaluated this drug for the topical treatment of CL. As efficacy depends on potency and skin penetration, we first determined its antileishmanial activity (IC50 = 100 μM) and selectivity index in vitro against Leishmania major-infected macrophages. In order to evaluate the skin penetration ex vivo, we compared an O/W cream containing DAP that had been micronized with a pluronic lecithin emulgel, in which the drug was solubilized with diethylene glycol monoethyl ether. For both formulations we obtained similar low flux values that increased when the stratum corneum and the epidermis were removed. In vivo efficacy studies performed on L. major-infected BALB/c mice revealed that treatment not only failed to cure the lesions but made their evolution and appearance worse. High plasma drug levels were detected and were concomitant with anemia and iron accumulation in the spleen. This side effect was correlated with a reduction of parasite burden in this organ. Our results evidenced that DAP in these formulations does not have an adequate safety index for use in the topical therapy of CL. Full article
(This article belongs to the Special Issue Drug Delivery for Anti-Infective Agents)
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Review

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32 pages, 1594 KiB  
Review
A Comprehensive Insight into the Role of Exosomes in Viral Infection: Dual Faces Bearing Different Functions
by Mabroka H. Saad, Raied Badierah, Elrashdy M. Redwan and Esmail M. El-Fakharany
Pharmaceutics 2021, 13(9), 1405; https://doi.org/10.3390/pharmaceutics13091405 - 4 Sep 2021
Cited by 44 | Viewed by 4081
Abstract
Extracellular vesicles (EVs) subtype, exosome is an extracellular nano-vesicle that sheds from cells’ surface and originates as intraluminal vesicles during endocytosis. Firstly, it was thought to be a way for the cell to get rid of unwanted materials as it loaded selectively with [...] Read more.
Extracellular vesicles (EVs) subtype, exosome is an extracellular nano-vesicle that sheds from cells’ surface and originates as intraluminal vesicles during endocytosis. Firstly, it was thought to be a way for the cell to get rid of unwanted materials as it loaded selectively with a variety of cellular molecules, including RNAs, proteins, and lipids. However, it has been found to play a crucial role in several biological processes such as immune modulation, cellular communication, and their role as vehicles to transport biologically active molecules. The latest discoveries have revealed that many viruses export their viral elements within cellular factors using exosomes. Hijacking the exosomal pathway by viruses influences downstream processes such as viral propagation and cellular immunity and modulates the cellular microenvironment. In this manuscript, we reviewed exosomes biogenesis and their role in the immune response to viral infection. In addition, we provided a summary of how some pathogenic viruses hijacked this normal physiological process. Viral components are harbored in exosomes and the role of these exosomes in viral infection is discussed. Understanding the nature of exosomes and their role in viral infections is fundamental for future development for them to be used as a vaccine or as a non-classical therapeutic strategy to control several viral infections. Full article
(This article belongs to the Special Issue Drug Delivery for Anti-Infective Agents)
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19 pages, 7439 KiB  
Review
Novel Strategy to Combat Antibiotic Resistance: A Sight into the Combination of CRISPR/Cas9 and Nanoparticles
by Fen Wan, Mohamed S. Draz, Mengjie Gu, Wei Yu, Zhi Ruan and Qixia Luo
Pharmaceutics 2021, 13(3), 352; https://doi.org/10.3390/pharmaceutics13030352 - 8 Mar 2021
Cited by 51 | Viewed by 8313
Abstract
Antibiotic resistance is a significant crisis that threatens human health and safety worldwide. There is an urgent need for new strategies to control multidrug-resistant (MDR) bacterial infections. The latest breakthrough in gene-editing tools based on CRISPR/Cas9 has potential application in combating MDR bacterial [...] Read more.
Antibiotic resistance is a significant crisis that threatens human health and safety worldwide. There is an urgent need for new strategies to control multidrug-resistant (MDR) bacterial infections. The latest breakthrough in gene-editing tools based on CRISPR/Cas9 has potential application in combating MDR bacterial infections because of their high targeting ability to specifically disrupt the drug resistance genes that microbes use for infection or to kill the pathogen directly. Despite the potential that CRISPR/Cas9 showed, its further utilization has been hampered by undesirable delivery efficiency in vivo. Nanotechnology offers an alternative way to overcome the shortcomings of traditional delivery methods of therapeutic agents. Advances in nanotechnology can improve the efficacy and safety of CRISPR/Cas9 components by using customized nanoparticle delivery systems. The combination of CRISPR/Cas9 and nanotechnology has the potential to open new avenues in the therapy of MDR bacterial infections. This review describes the recent advances related to CRISPR/Cas9 and nanoparticles for antimicrobial therapy and gene delivery, including the improvement in the packaging and localizing efficiency of the CRISPR/Cas9 components in the NP (nanoparticle)/CRISPR system. We pay particular attention to the strengths and limitations of the nanotechnology-based CRISPR/Cas9 delivery system to fight nosocomial pathogens.We highlight the need for more scientific research to explore the combinatorial efficacy of various nanoparticles and CRISPR technology to control and prevent antimicrobial resistance. Full article
(This article belongs to the Special Issue Drug Delivery for Anti-Infective Agents)
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15 pages, 1228 KiB  
Review
Bacteriocins in the Era of Antibiotic Resistance: Rising to the Challenge
by Gratiela Gradisteanu Pircalabioru, Laura Ioana Popa, Luminita Marutescu, Irina Gheorghe, Marcela Popa, Ilda Czobor Barbu, Rodica Cristescu and Mariana-Carmen Chifiriuc
Pharmaceutics 2021, 13(2), 196; https://doi.org/10.3390/pharmaceutics13020196 - 2 Feb 2021
Cited by 69 | Viewed by 7286
Abstract
Decades of antibiotic misuse in clinical settings, animal feed, and within the food industry have led to a concerning rise in antibiotic-resistant bacteria. Every year, antimicrobial-resistant infections cause 700,000 deaths, with 10 million casualties expected by 2050, if this trend continues. Hence, innovative [...] Read more.
Decades of antibiotic misuse in clinical settings, animal feed, and within the food industry have led to a concerning rise in antibiotic-resistant bacteria. Every year, antimicrobial-resistant infections cause 700,000 deaths, with 10 million casualties expected by 2050, if this trend continues. Hence, innovative solutions are imperative to curb antibiotic resistance. Bacteria produce a potent arsenal of drugs with remarkable diversity that are all distinct from those of current antibiotics. Bacteriocins are potent small antimicrobial peptides synthetized by certain bacteria that may be appointed as alternatives to traditional antibiotics. These molecules are strategically employed by commensals, mostly Firmicutes, to colonize and persist in the human gut. Bacteriocins form channels in the target cell membrane, leading to leakage of low-molecular-weight, causing the disruption of the proton motive force. The objective of this review was to list and discuss the potential of bacteriocins as antimicrobial therapeutics for infections produced mainly by resistant pathogens. Full article
(This article belongs to the Special Issue Drug Delivery for Anti-Infective Agents)
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15 pages, 1603 KiB  
Review
Potential Novel Food-Related and Biomedical Applications of Nanomaterials Combined with Bacteriocins
by Atanu Naskar and Kwang-sun Kim
Pharmaceutics 2021, 13(1), 86; https://doi.org/10.3390/pharmaceutics13010086 - 11 Jan 2021
Cited by 37 | Viewed by 3961
Abstract
Bacteriocins are antimicrobial peptides or proteinaceous materials produced by bacteria against pathogens. These molecules have high efficiency and specificity and are equipped with many properties useful in food-related applications, such as food preservatives and additives, as well as biomedical applications, such as serving [...] Read more.
Bacteriocins are antimicrobial peptides or proteinaceous materials produced by bacteria against pathogens. These molecules have high efficiency and specificity and are equipped with many properties useful in food-related applications, such as food preservatives and additives, as well as biomedical applications, such as serving as alternatives to current antibacterial, antiviral, anticancer, and antibiofilm agents. Despite their advantages as alternative therapeutics over existing strategies, several limitations of bacteriocins, such as the high cost of isolation and purification, narrow spectrum of activity, low stability and solubility, and easy enzymatic degradation, need to be improved. Nanomaterials are promising agents in many biological applications. They are widely used in the conjugation or decoration of bacteriocins to augment the activity of bacteriocins or reduce problems related to their use in biomedical applications. Therefore, bacteriocins combined with nanomaterials have emerged as promising molecules that can be used in various biomedical applications. This review highlights the features of bacteriocins and their limitations in biomedical applications and provides a detailed overview of the uses of different nanomaterials in improving the limitations. Our review focuses on the potential applications of nanomaterials combined with bacteriocins as new designer molecules for use in future therapeutic strategies. Full article
(This article belongs to the Special Issue Drug Delivery for Anti-Infective Agents)
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47 pages, 2530 KiB  
Review
A Critical Review on Emerging Trends in Dry Powder Inhaler Formulation for the Treatment of Pulmonary Aspergillosis
by Shen Nam Cheng, Zhi Guang Tan, Manisha Pandey, Teerapol Srichana, Mallikarjuna Rao Pichika, Bapi Gorain and Hira Choudhury
Pharmaceutics 2020, 12(12), 1161; https://doi.org/10.3390/pharmaceutics12121161 - 28 Nov 2020
Cited by 10 | Viewed by 4016
Abstract
Pulmonary aspergillosis (PA), a pulmonary fungal infection caused by Aspergillus spp., is a concern for immunocompromised populations. Despite substantial research efforts, conventional treatments of PA using antifungal agents are associated with limitations such as excessive systemic exposure, serious side effects and limited availability [...] Read more.
Pulmonary aspergillosis (PA), a pulmonary fungal infection caused by Aspergillus spp., is a concern for immunocompromised populations. Despite substantial research efforts, conventional treatments of PA using antifungal agents are associated with limitations such as excessive systemic exposure, serious side effects and limited availability of the therapeutics in the lungs for an adequate duration. To overcome the limitations associated with the conventional regimens, pulmonary delivery of antifungal agents has become a focal point of research because of the superiority of local and targeted drug delivery. Dry powder inhalers and nebulized formulations of antifungal agents have been developed and evaluated for their capability to effectively deliver antifungal agents to the lungs. Moreover, progress in nanotechnology and the utilization of nanocarriers in the development of pulmonary delivery formulations has allowed further augmentation of treatment capability and efficiency. Thus, the following review provides an insight into the advantages and therapeutic potential of the utilization of nanocarriers in pulmonary delivery of antifungal agents for the treatment of PA. In addition, discussions on formulation aspects and safety concerns together with the clinical and regulatory aspects of the formulations are presented, which suggest the possibility and desirability of utilization of nanocarriers in the treatment of PA. Full article
(This article belongs to the Special Issue Drug Delivery for Anti-Infective Agents)
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17 pages, 2164 KiB  
Review
Engineered Cationic Antimicrobial Peptides (eCAPs) to Combat Multidrug-Resistant Bacteria
by Berthony Deslouches, Ronald C. Montelaro, Ken L. Urish and Yuanpu P. Di
Pharmaceutics 2020, 12(6), 501; https://doi.org/10.3390/pharmaceutics12060501 - 30 May 2020
Cited by 43 | Viewed by 6073
Abstract
The increasing rate of antibiotic resistance constitutes a global health crisis. Antimicrobial peptides (AMPs) have the property to selectively kill bacteria regardless of resistance to traditional antibiotics. However, several challenges (e.g., reduced activity in the presence of serum and lack of efficacy in [...] Read more.
The increasing rate of antibiotic resistance constitutes a global health crisis. Antimicrobial peptides (AMPs) have the property to selectively kill bacteria regardless of resistance to traditional antibiotics. However, several challenges (e.g., reduced activity in the presence of serum and lack of efficacy in vivo) to clinical development need to be overcome. In the last two decades, we have addressed many of those challenges by engineering cationic AMPs de novo for optimization under test conditions that typically inhibit the activities of natural AMPs, including systemic efficacy. We reviewed some of the most promising data of the last two decades in the context of the advancement of the field of helical AMPs toward clinical development. Full article
(This article belongs to the Special Issue Drug Delivery for Anti-Infective Agents)
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20 pages, 768 KiB  
Review
Recent Advances in Nanomaterial-Based Wound-Healing Therapeutics
by Atanu Naskar and Kwang-sun Kim
Pharmaceutics 2020, 12(6), 499; https://doi.org/10.3390/pharmaceutics12060499 - 30 May 2020
Cited by 155 | Viewed by 7638
Abstract
Nanomaterial-based wound healing has tremendous potential for treating and preventing wound infections with its multiple benefits compared with traditional treatment approaches. In this regard, the physiochemical properties of nanomaterials enable researchers to conduct extensive studies on wound-healing applications. Nonetheless, issues concerning the use [...] Read more.
Nanomaterial-based wound healing has tremendous potential for treating and preventing wound infections with its multiple benefits compared with traditional treatment approaches. In this regard, the physiochemical properties of nanomaterials enable researchers to conduct extensive studies on wound-healing applications. Nonetheless, issues concerning the use of nanomaterials in accelerating the efficacy of existing medical treatments remain unresolved. The present review highlights novel approaches focusing on the recent innovative strategies for wound healing and infection controls based on nanomaterials, including nanoparticles, nanocomposites, and scaffolds, which are elucidated in detail. In addition, the efficacy of nanomaterials as carriers for therapeutic agents associated with wound-healing applications has been addressed. Finally, nanomaterial-based scaffolds and their premise for future studies have been described. We believe that the in-depth analytical review, future insights, and potential challenges described herein will provide researchers an up-to-date reference on the use of nanomedicine and its innovative approaches that can enhance wound-healing applications. Full article
(This article belongs to the Special Issue Drug Delivery for Anti-Infective Agents)
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