Novel two-chain fatty acid-based lipids for development of vancomycin pH-responsive liposomes against <i>Staphylococcus aureus</i> and methicillin-resistant <i>Staphylococcus aureus</i> (MRSA)

Makhathini, Sifiso S.; Kalhapure, Rahul S.; Jadhav, Mahantesh; Waddad, Ayman Y.; Gannimani, Ramesh; Omolo, Calvin A.; Rambharose, Sanjeev; Mocktar, Chunderika; Govender, Thirumala

doi:10.1080/1061186x.2019.1599380

Cited by 27 publications

(9 citation statements)

References 57 publications

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“…reversal from being positively to negatively charged. Zwitterionic lipids have both acidic and alkaline functional groups (Figure 5; Hu et al, 2019;Makhathini et al, 2019) that allow full charge reversal below and above their iso-electric point (Figure 8A; Vila-Caballer et al, 2016;Liu et al, 2018). This feature allows the fabrication of liposomes that are negatively-charged under physiological pH conditions and become positivelycharged under more acidic conditions, such as poly(methacryloyl sulfadimethoxine) (PSD) liposomes (Figure 8B; Couffin-Hoarau and Leroux, 2004;Ghattas and Leroux, 2009;Lu et al, 2018).…”

Section: Zwitterionic Liposomesmentioning

confidence: 99%

Lipid-Based Antimicrobial Delivery-Systems for the Treatment of Bacterial Infections

et al. 2020

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Many nanotechnology-based antimicrobials and antimicrobial-delivery-systems have been developed over the past decades with the aim to provide alternatives to antibiotic treatment of infectious-biofilms across the human body. Antimicrobials can be loaded into nanocarriers to protect them against de-activation, and to reduce their toxicity and potential, harmful side-effects. Moreover, antimicrobial nanocarriers such as micelles, can be equipped with stealth and pH-responsive features that allow self-targeting and accumulation in infectious-biofilms at high concentrations. Micellar and liposomal nanocarriers differ in hydrophilicity of their outer-surface and inner-core. Micelles are self-assembled, spherical core-shell structures composed of single layers of surfactants, with hydrophilic head-groups and hydrophobic tail-groups pointing to the micellar core. Liposomes are composed of lipids, self-assembled into bilayers. The hydrophilic head of the lipids determines the surface properties of liposomes, while the hydrophobic tail, internal to the bilayer, determines the fluidity of liposomal-membranes. Therefore, whereas micelles can only be loaded with hydrophobic antimicrobials, hydrophilic antimicrobials can be encapsulated in the hydrophilic, aqueous core of liposomes and hydrophobic or amphiphilic antimicrobials can be inserted in the phospholipid bilayer. Nanotechnology-derived liposomes can be prepared with diameters <100-200 nm, required to prevent reticulo-endothelial rejection and allow penetration into infectious-biofilms. However, surface-functionalization of liposomes is considerably more difficult than of micelles, which explains while self-targeting, pH-responsive liposomes that find their way through the blood circulation toward infectious-biofilms are still challenging to prepare. Equally, development of liposomes that penetrate over the entire thickness of biofilms to provide deep killing of biofilm inhabitants still provides a challenge. The liposomal phospholipid bilayer easily fuses with bacterial cell membranes to release high antimicrobial-doses directly inside bacteria. Arguably, protection against de-activation of antibiotics in liposomal nanocarriers and their fusogenicity constitute the biggest advantage of liposomal antimicrobial carriers over antimicrobials free in solution. Many Gram-negative and Gram-positive bacterial strains, resistant to specific antibiotics, Wang et al. Lipid-Based Antimicrobial Delivery-Systems have been demonstrated to be susceptible to these antibiotics when encapsulated in liposomal nanocarriers. Recently, also progress has been made concerning large-scale production and long-term storage of liposomes. Therewith, the remaining challenges to develop self-targeting liposomes that penetrate, accumulate and kill deeply in infectious-biofilms remain worthwhile to pursue.

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Section: Zwitterionic Liposomesmentioning

confidence: 99%

Lipid-Based Antimicrobial Delivery-Systems for the Treatment of Bacterial Infections

et al. 2020

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“…Liposomes deliver higher concentration of vancomycin to lung tissue while reducing accumulation in kidney tissue 133 ; surface PEGylation augments this effect 134 . Novel fatty acid‐based zwitterionic lipids have been used to develop pH‐responsive liposomes for the targeted delivery of vancomycin to acidic environments 135 . Bacteria thrive in these conditions whereas antibiotics often lose their activity.…”

Section: Potential Strategies For Preventionmentioning

confidence: 99%

Vancomycin‐Induced Kidney Injury: Animal Models of Toxicodynamics, Mechanisms of Injury, Human Translation, and Potential Strategies for Prevention

et al. 2020

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Vancomycin is a recommended therapy in multiple national guidelines. Despite the common use, there is a poor understanding of the mechanistic drivers and potential modifiers of vancomycin-mediated kidney injury. In this review, historic and contemporary rates of vancomycin-induced kidney injury (VIKI) are described, and toxicodynamic models and mechanisms of toxicity from preclinical studies are reviewed. Aside from known clinical covariates that worsen VIKI, preclinical models have demonstrated that various factors impact VIKI, including dose, route of administration, and thresholds for pharmacokinetic parameters. The degree of acute kidney injury (AKI) is greatest with the intravenous route and higher doses that produce larger maximal concentrations and areas under the concentration curve. Troughs (i.e., minimum concentrations) have less of an impact. Mechanistically, preclinical studies have identified that VIKI is a result of drug accumulation in proximal tubule cells, which triggers cellular oxidative stress and apoptosis. Yet, there are several gaps in the knowledge that may represent viable targets to make vancomycin therapy less toxic. Potential strategies include prolonging infusions and lowering maximal concentrations, administration of antioxidants, administering agents that decrease cellular accumulation, and reformulating vancomycin to alter the renal clearance mechanism. Based on preclinical models and mechanisms of toxicity, we propose potential strategies to lessen VIKI.

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“…This was the first report of designed PSLs for the enhancement of antibiotic efficacy through targeting of the bacterial infection site. The same research group reported another very similar study a year later, using a new class of two chain fatty acid‐derived lipids incorporating amino acid head groups for the formulation of targeted pH‐sensitive vancomycin‐loaded antibacterial liposomes (Makhathini et al, 2019). The fatty acids are the same as those used in the previous study, producing four different pH‐sensitive lipids using a 2‐amino‐1,3‐propanediol as a linker (DSAPA, DOAPA, DLAPA, and DLLAPA) (Table 5).…”

Section: Intrinsic Stimuli‐responsive Nanocarriers For Antibacterial mentioning

confidence: 97%

Intrinsic stimuli‐responsive nanocarriers for smart drug delivery of antibacterial agents—An in‐depth review of the last two decades

Devnarain

Osman

Fasiku

et al. 2020

WIREs Nanomed Nanobiotechnol

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Antibiotic resistance due to suboptimal targeting and inconsistent antibiotic release at bacterial infection sites has driven the formulation of stimuli‐responsive nanocarriers for antibacterial therapy. Unlike conventional nanocarriers, stimuli‐responsive nanocarriers have the ability to specifically enhance targeting and drug release profiles. There has been a significant escalation in the design and development of novel nanomaterials worldwide; in particular, intrinsic stimuli‐responsive antibiotic nanocarriers, due to their enhanced activity, improved targeted delivery, and superior potential for bacterial penetration and eradication. Herein, we provide an extensive and critical review of pH‐, enzyme‐, redox‐, and ionic microenvironment‐responsive nanocarriers that have been reported in literature to date, with an emphasis on the mechanisms of drug release, the nanomaterials used, the nanosystems constructed and the antibacterial efficacy of the nanocarriers. The review also highlights further avenues of research for optimizing their potential and commercialization. This review confirms the potential of intrinsic stimuli‐responsive nanocarriers for enhanced drug delivery and antibacterial killing. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

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Novel two-chain fatty acid-based lipids for development of vancomycin pH-responsive liposomes against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA)

Cited by 27 publications

References 57 publications

Lipid-Based Antimicrobial Delivery-Systems for the Treatment of Bacterial Infections

Lipid-Based Antimicrobial Delivery-Systems for the Treatment of Bacterial Infections

Vancomycin‐Induced Kidney Injury: Animal Models of Toxicodynamics, Mechanisms of Injury, Human Translation, and Potential Strategies for Prevention

Intrinsic stimuli‐responsive nanocarriers for smart drug delivery of antibacterial agents—An in‐depth review of the last two decades

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