External factors affecting the linear and nonlinear rheological behavior of oleogel-based emulsions.

This study reported oleogel-based emulsions (OGEs, W/O) stabilized by carnauba wax. The effects of different external factors (heating temperature, crystallization temperature, and shear application during crystallization) on the microstructure and linear/nonlinear rheological properties of OGEs were investigated. Microstructural observation suggested that the OGEs had a uniform droplet distribution, and the carnauba wax crystals trapped oil in the continuous phase. The gelatinized oil phase allowed the OGEs to have a solid appearance and typical yielding behavior. The small amplitude oscillation shear analysis showed that lower heating temperature, higher crystallization temperature, and suitable shear application resulted in a stronger, more stable, and tighter packed network structure and better resistance to deformation of the OGEs. For nonlinear behavior, the elastic dominant behavior of OGEs transformed into viscous dominant behavior at large strain amplitudes, accompanied by more energy dissipation, strain stiffening, and a transition from shear thickening to shear thinning.

Unleashing the Potential: Designing Antibody-Targeted Lipid Nanoparticles for Industrial Applications with CMC Considerations and Clinical Outlook.

Antibody-targeted lipid nanoparticles (Ab-LNPs) are rapidly gaining traction as multifaceted platforms in precision medicine, adept at delivering a diverse array of therapeutic agents, including nucleic acids and small molecules. This review provides an incisive overview of the latest developments in the field of Ab-LNP technology, with a special emphasis on pivotal design aspects such as antibody engineering, bioconjugation strategies, and advanced formulation techniques. Furthermore, it addresses critical chemistry, manufacturing, and controls (CMC) considerations and thoroughly examines the in vivo dynamics of Ab-LNPs, underscoring their promising potential for clinical application. By seamlessly blending scientific advancements with practical industrial perspectives, this review casts a spotlight on the burgeoning role of Ab-LNPs as an innovative and potent tool in the realm of targeted drug delivery.

Protocatechuic acid and gallic acid improve the emulsion and thermal stability of whey protein by covalent binding.

This study aimed to explore the impacts of gallic acid (GA)/protocatechuic acid (PA) on the structural and functional characteristics of whey proteins (WP) through covalent binding. To this purpose, the covalent complexes of WP-PA and WP-GA at different concentration gradients were prepared by the alkaline method. SDS-PAGE indicated that PA/GA was cross-linked by covalent bonds. The decreased contents of free amino and sulfhydryl groups suggested that WP formed covalent bonds with PA/GA by amino and sulfhydryl groups, and the structure of WP became slightly looser after covalent modification by PA/GA. When the concentration of GA was added up to 10 mM, the structure of WP was slightly loosened with a reduction of α-helix content by 2.3% and an increase in random coil content by 3.0%. The emulsion stability index of WP increased by 14.9 min after interaction with GA. Moreover, the binding of WP and 2-10 mM PA/GA increased the denaturation temperature by 1.95 to 19.87 °C, indicating the improved thermal stability of the PA/GA-WP covalent complex. Additionally, the antioxidant capacity of WP was increased with increasing GA/PA concentration. This work may offer worthful information for enhancing the functional properties of WP and the application of the PA/GA-WP covalent complexes in food emulsifiers.

Oleogel-structured emulsions: A review of formation, physicochemical properties and applications.

Oleogel-structured emulsion (OGE) is an emulsion in which the presence of oleogelator in the oil phase causes the oil phase to change from a liquid to a solid state. OGEs are increasingly being explored for their better stability, delivery efficiency, and adjustable rheological properties compared with conventional emulsions. However, many oleogelators are relatively unstable in the presence of water, and a good understanding of the relationship between emulsification and oleogelator as well as the synergistic or antagonistic effects on emulsion formation, structure, and functionality is required. Hence, the question arises whether different kinds of oleogelators are feasible in the preparation of OGEs. This review aims to assess the relationship between the oleogelator and emulsifiers or aqueous phases. Moreover, the fabrication methods, physicochemical properties, and applications are reviewed. It can be concluded that the food industry may have a great revolution with the development of OGEs.

Drug Stability and Minimized Acid-/Drug-Catalyzed Phospholipid Degradation in Liposomal Irinotecan.

Therapeutics at or close to the nanoscale, such as liposomal irinotecan, offer significant promise for the treatment of solid tumors. Their potential advantage over the unencapsulated or free form of the drug is due in part to their altered biodistribution. For slow and sustained release, significant optimization of formulation is needed to achieve the required level of stability and allow long-term storage of the drug product. Gradient-based liposomal formulation of camptothecins such as irinotecan poses unique challenges owing to the camptothecin- and acid-catalyzed hydrolysis of phospholipid esters in the inner monolayer of the liposomal membrane. We demonstrated that a narrow set of conditions related to the external pH, temperature, intraliposomal concentration, identity of the drug-trapping agent, physical form of the drug inside the liposomes, and final drug load have a marked impact on the stability of the liposome phospholipid membrane. The physical form of the drug inside the liposome was shown to be an insoluble gel with an irinotecan-to-sulfate ratio approximating 1:1, reducing the potential for irinotecan-catalyzed phospholipid hydrolysis in the internal phospholipid monolayer. As a result of this work, a stable and active liposome formulation has been developed that maintains phospholipid chemical stability following long-term storage at 2-8°C.

Structure Identification and Functional Mechanism of Natural Active Components: A Special Issue.

The natural active components derived from plants have attracted widespread attention due to their abundant species and source advantages [...].

Microcapsules with slow-release characteristics prepared by soluble small molecular starch fractions through the spray drying method.

The utilization of starch in the food and medical industry can be facilitated by using new non-chemical methods to make starch the only wall material to encapsulate microcapsules. In this study, soluble small molecular fraction obtained from corn starch by gelatinization and centrifugation methods and commercial soluble starch were used independently to encapsulate oil under the condition that wall material and core material were 2:1. Molecular weight of these starch fractions was measured firstly. The peak molecular weight of the soluble small molecular fraction of corn starch and commercial soluble starch was 3.537 × 105 Da and 2.720 × 104 Da, respectively. Basic physicochemical characteristics and application characteristics of the microcapsules were then characterized and compared. The soluble small molecular fraction of corn starch encapsulated microcapsule and the commercial soluble starch encapsulated microcapsule had high encapsulation efficiency (higher than 88%), high boiling water solubility (higher than 74%), high rehydration stability (higher than 2 h). Most importantly, the encapsulated oil of these microcapsules could be slowly released under the action of α-amylase and amyloglucosidase. Overall, both the soluble small molecular fraction of corn starch and commercial soluble starch could be used as microcapsule wall materials and might have great application potential in food and medicine.

Liposomal encapsulation of trans-crocetin enhances oxygenation in patients with COVID-19-related ARDS receiving mechanical ventilation.

Current therapeutic treatments improving the impaired transportation of oxygen in acute respiratory distress syndrome (ARDS) have been found to be relevant and beneficial for the therapeutic treatment of COVID-19 patients suffering from severe respiratory complications. Hence, we report the preclinical and the preliminary results of the Phase I/II clinical trial of LEAF-4L6715, a liposomal nanocarrier encapsulating the kosmotropic agent trans-crocetin (TC), which, once injected, enhance the oxygenation of vascular tissue and therefore has the potential to improve the clinical outcomes of ARDS and COVID-19 in severely impacted patients. We demonstrated that the liposomal formulation enabled to increase from 30 min to 48 h the reoxygenation properties of free TCs in vitro in endothelial cells, but also to improve the half-life of TC by 6-fold in healthy mice. Furthermore, we identified 25 mg/kg as the maximum tolerated dose in mice. This determined concentration led to the validation of the therapeutic efficacy of LEAF-4 L6715 in a sepsis mouse model. Finally, we report the preliminary outcomes of an open-label multicenter Phase I/II clinical trial (EudraCT 2020-001393-30; NCT04378920), which was aimed to define the appropriate schedule and dosage of LEAF-4L6715 and to confirm its tolerability profile and preliminary clinical activity in COVID-19 patients treated in intensive care unit.

Fabrication and characterization of the W/O/W multiple emulsion through oleogelation of oil.

W/O/W emulsions were easily prepared by oleogelation of the oil phase using rice bran wax (RBX) and their microstructure, stability, rheology and protection of proanthocyanidins and ß-carotene were investigated. Formation of the W/O/W emulsion was confirmed using confocal laser scanning microscopy and staining of the inner aqueous phase by tartrazine. The average particle size and viscosity of the emulsion increased as the RBX concentration increased. Moreover, RBX increased the stability of the emulsion and the emulsion was the most stable when the RBX concentration was 8.0% or 10.0%. On the other hand, the W/O/W emulsions were used to simultaneously encapsulate proanthocyanidins and ß-carotene. Specifically, proanthocyanidins and ß-carotene in RBX-containing emulsions were more stable and had higher bioaccessibility than in the emulsion without RBX. Besides, both their chemical stability and bioaccessibility reached the maximum value when the RBX concentration was 8.0% or 10.0%. In summary, the optimal RBX concentration was 8.0%.

Targeting EphA2 in Bladder Cancer Using a Novel Antibody-Directed Nanotherapeutic.

Ephrin receptor A2 (EphA2) is a member of the Ephrin/Eph receptor cell-to-cell signaling family of molecules, and it plays a key role in cell proliferation, differentiation, and migration. EphA2 is overexpressed in a broad range of cancers, and its expression is in many cases associated with poor prognosis. We recently developed a novel EphA2-targeting antibody-directed nanotherapeutic encapsulating a labile prodrug of docetaxel (EphA2-ILs-DTXp) for the treatment of EphA2-expressing malignancies. Here, we characterized the expression of EphA2 in bladder cancer using immunohistochemistry in 177 human bladder cancer samples and determined the preclinical efficacy of EphA2-ILs-DTXp in four EphA2-positive patient-derived xenograft (PDX) models of the disease, either as a monotherapy, or in combination with gemcitabine. EphA2 expression was detected in 80-100% of bladder cancer samples and correlated with shorter patient survival. EphA2 was found to be expressed in tumor cells and/or tumor-associated blood vessels in both primary and metastatic lesions with a concordance rate of approximately 90%. The EphA2-targeted antibody-directed nanotherapeutic EphA2-ILs-DTXp controlled tumor growth, mediated greater regression, and was more active than free docetaxel at equitoxic dosing in all four EphA2-positive bladder cancer PDX models. Combination of EphA2-ILs-DTXp and gemcitabine in one PDX model led to improved tumor growth control compared to monotherapies or the combination of free docetaxel and gemcitabine. These data demonstrating the prevalence of EphA2 in bladder cancers and efficacy of EphA2-ILs-DTXp in PDX models support the clinical exploration of EphA2 targeting in bladder cancer.

Annealing treatment of amylose and amylopectin extracted from rice starch.

Annealing behavior of amylose and amylopectin was unclear. In this work, high purity amylose and amylopectin were extracted from rice starch, and structural properties of the retrograded rice starch, amylose, and amylopectin before and after annealing treatment were explored. It was found that the purity of the amylose and amylopectin was 95.64% ±â€¯2.69% and 94.98% ±â€¯0.97%, respectively. Their molecular weight was (2.93 ±â€¯0.21) × 106 Da and (5.90 ±â€¯0.13) × 107 Da, respectively. Besides, the relative crystallinities and ratios of 1047 cm-1/1022 cm-1 of the retrograded rice starch and amylose were significantly increased by annealing treatment, while that of retrograded amylopectin did not change. These results clarified that amylose was more sensitive to annealing treatment than amylopectin, and amylose was more responsible for annealing of starch than amylopectin. The findings contributed to a better understanding of the annealing behavior of starch.

Stabilization of peanut butter by rice bran wax.

To improve stability of peanut butter, rice bran wax (RBX) was added into peanut butter as a stabilizer by formation of organogel. Effects of addition of RBX, heating temperature, and cooling temperature on stabilization effect of peanut butter by RBX were investigated. The optimum conditions were as follow: addition of RBX at 4.0 wt%; heating temperature at 85 °C, and cooling temperature at 20 °C. Under the optimum conditions, the oil loss of peanut butter decreased from 12.19% to 4.04%, and the adhesiveness of peanut butter increased from 23.5 to 165.9 g·s. After storage for 25 weeks, the acid value (AV) of peanut butter prepared under the optimum conditions increased from 0.65  to 0.80 mg/g, and the peroxide value (PV) increased from 0.116 to 0.127 meq/kg. However, the AV of natural peanut butter increased to 1.73 mg/g, and PV increased to 0.178 meq/kg. The confocal laser scanning microscope images showed that the cooling temperature significantly affected crystallization of RBX and distribution of solid particles. When RBX formed needle-like crystals and peanut solid particles were evenly distributed in the oil phase, stable peanut butter was obtained. These results suggested that the RBX was an effective stabilizer for peanut butter. PRACTICAL APPLICATION: Oil separation often occurred to peanut butter during storage, which reduced the sensory quality of peanut butter and shortened its shelf life. This study stabilized peanut butter by addition of RBX based on the formation of organogel, which was of great practical significance to improve the shelf life of peanut butter.

Preparation and characterization of octenyl succinate ß-limit dextrin.

Waxy rice starch was hydrolyzed by ß-amylase and then modified by octenyl succinic anhydride (OSA) to prepare octenyl succinate ß-limit dextrin (OSA ß-limit dextrin). Subsequently, structure, digestibility and emulsifying capacity of OSA ß-limit dextrin were measured. The FT-IR analysis confirmed formation of OSA ß-limit dextrin. When the addition of OSA was 1.0%, 2.0% and 3.0%, the DS of OSA ß-limit dextrin was 0.006, 0.011 and 0.019, respectively. The molecular weight, resistant starch content and emulsifying capacity of OSA ß-limit dextrin was higher than ß-limit dextrin and increased with the increasing of DS. In addition, the solubility of OSA ß-limit dextrin reached 100%. The emulsion prepared by OSA ß-limit dextrin was stable at pH 3.0-7.0 and became unstable at pH 8.0-11.0 or after addition of NaCl. These results suggested that OSA ß-limit dextrin was safe soluble resistant dextrin with emulsifying ability, which might be used in functional food and beverage products.

Synergy between EphA2-ILs-DTXp, a Novel EphA2-Targeted Nanoliposomal Taxane, and PD-1 Inhibitors in Preclinical Tumor Models.

Combinations of chemotherapy with immunotherapy have seen recent clinical success, including two approvals of anti-PD-1/L1 agents in combination with taxane-based chemotherapy in non-small cell lung cancer and triple-negative breast cancer. Here, we present a study on the combination activity and mechanistic rationale of a novel EphA2-targeted liposomal taxane (EphA2-ILs-DTXp) and anti-PD-1. This combination was highly active in mouse syngeneic tumor models, with complete responses observed in 3 of 5 models. In the EMT-6 tumor model, combination of EphA2-ILs-DTXp with anti-PD-1 resulted in a 60% complete response rate, with durable responses that were resistant to rechallenge. These responses were not observed in the absence of CD8+ T cells. Characterization of the immune infiltrates in EMT-6 tumors reveals increased CD8+ T cells, increased CD8+ IFNγ+ CTLs, and an increased CD8/regulatory T-cell (Treg) ratio. These immunomodulatory effects were not observed in mice treated with a combination of docetaxel and anti-PD-1. Pharmacokinetic analysis revealed that the AUC of docetaxel was increased 15 times, from 52.1 to 785 ng/mL/hour, when delivered by EphA2-ILs-DTXp. A dose reduction study of EphA2-ILs-DTXp showed a dose-response relationship for both tumor growth inhibition and the CD8/Treg ratio. Our data indicate that synergism between docetaxel and anti-PD-1 is achievable with nanoliposomal delivery.

Formulation optimization of an ephrin A2 targeted immunoliposome encapsulating reversibly modified taxane prodrugs.

Ephrin A2 targeted immunoliposomes incorporating pH-sensitive taxane prodrugs were developed for sustained delivery of active drug to solid tumors. Here we describe the systematic formulation development and characterization of these immunoliposomes. We synthesized both paclitaxel and docetaxel prodrugs to formulate as ephrin A2-targeted liposomes stabilized in the aqueous core with sucroseoctasulfate (SOS). The optimized lipid formulation was comprised of egg-sphingomyelin, cholesterol, and polyethylene glycol distearoyl glycerol (PEG-DSG). The formulations examined had a high efficiency of prodrug encapsulation (as high as 114 mol% taxane per mole phospholipid) and subsequent stability (>3 years at 2-8 °C). The taxane prodrug was stabilized with extraliposomal citric acid and subsequently loaded into liposomes containing a gradient of SOS, resulting in highly stable SOS-drug complexes being formed inside the liposome. The internal prodrug and SOS concentrations were optimized for their impact on in vivo drug release and drug degradation. Cryo-electron microscope images revealed dense prodrug-SOS complex in the aqueous core of the immunoliposomes. Ephrin A2-targeted taxane liposomes exhibited sub-nanomolar (0.69 nM) apparent equilibrium dissociation constant toward the extracellular domain of the ephrin A2 receptor, long circulation half-life (8-12 h) in mouse plasma, a release rate dependent on intraliposomal drug concentration and stable long-term storage. At an equitoxic dose of 50 mg taxane/kg, ephrin A2-targeted liposomal prodrug showed greater antitumor activity than 10 mg/kg of docetaxel in A549 non-small cell lung, as well as MDA-MB-436 and SUM149 triple negative breast cancer xenograft models. The lead molecule entered a Phase I clinical trial in patients with solid tumors (NCT03076372).

[One-stage debridement and two-stage Ilizarov bone transport technology for post-traumatic lateral malleolus defect].

OBJECTIVE: To explore the effectiveness of one-stage debridement and two-stage Ilizarov bone transport technology in repairing post-traumatic lateral malleolus defect. METHODS: Between June 2013 and December 2016, 7 patients with bone defect of lateral malleolus were treated. There were 5 males and 2 females with an average age of 45.9 years (range, 35-60 years). There were 6 cases of traffic accident injury and 1 case of strangulation injury. All patients had extensive soft tissue injury and lateral malleolus bone exposure. There were 4 cases of Gustilo type ⅢB and 3 case of Gustilo type ⅢC. The time from injury to admission was 3-10 hours (mean, 6.3 hours). Through one-stage thorough debridement, exploration and repair of vessels and nerves, external fixation of scaffolds and coverage of wounds, free fibulas were removed in 3 cases at one-stage and fibulas were resected in 4 cases after expansion. The bone defects ranged from 4.5 to 15.0 cm in length (mean, 8.2 cm). The Ilizarov circular external fixators were used to transport with fibula osteotomy for repairing bone defect of lateral malleolus when the wound healing. RESULTS: During fibular osteotomy, the stents were adjusted 2-4 times (mean, 2.8 times) and the external fixators were removed after 10-16 months (mean, 12.8 months). The nail tract infection occurred in 2 cases during transporting and was controlled after symptomatic treatment. All patients were followed up 24-48 months (mean, 32.9 months). The shape of lateral malleolus was close to normal without obvious varus or valgus deformity. American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hind foot score was 86-92 (mean, 90.3), and 5 cases were excellent and 2 cases were good. X-ray film showed that there was no obvious widening of the gap between the ankle points and no sign of absorption of the lateral malleolus. CONCLUSION: The one-stage debridement combined with two-stage Ilizarov bone transport technology can maintain the stability of ankle joint structure and obtain better effectiveness in repairing post-traumatic lateral malleolus defect.

Antitumour activity and tolerability of an EphA2-targeted nanotherapeutic in multiple mouse models.

Antibody-mediated tumour targeting and nanoparticle-mediated encapsulation can reduce the toxicity of antitumour drugs and improve their efficacy. Here, we describe the performance of a nanotherapeutic encapsulating a hydrolytically sensitive docetaxel prodrug and conjugated to an antibody specific for EphA2-a receptor overexpressed in many tumours. Administration of the nanotherapeutic in mice led to slow and sustained release of the prodrug, reduced exposure of active docetaxel in the circulation (compared with administration of the free drug) and maintenance of optimal exposure of the drug in tumour tissue. We also show that administration of the nanotherapeutic in rats and dogs resulted in minimal haematological toxicity, as well as the absence of neutropenia and improved overall tolerability in multiple rodent models. Targeting of the nanotherapeutic to EphA2 improved tumour penetration and resulted in markedly enhanced antitumour activity (compared with administration of free docetaxel and non-targeted nanotherapeutic controls) in multiple tumour-xenografted mice. This nanomedicine could become a potent and safe therapeutic alternative for cancer patients undergoing chemotherapy.

Microbial community evolution and fate of antibiotic resistance genes along six different full-scale municipal wastewater treatment processes.

The evolution of microbial community and the fate of ARGs along different full-scale wastewater treatment processes (i.e., Anaerobic-Anoxic-Oxic, Oxidation Ditch, and Cyclic Activated Sludge System) were investigated in this study. We found that the sludges of bioreactors treating similar influent showed the similar microbial communities, independent of the treatment technologies. The horizontal gene transfer (HGT) mainly occurred in aeration tank rather that anaerobic/anoxic tank. More co-occurrence of potential pathogens and ARGs was found in wastewater than in sludge. Microbial biomass was the key driver for the fate of ARGs in wastewater, while mobile genetic elements (MGEs) was the key factor for the fate of ARGs in sludge. Combination of wastewater characteristics, microbial diversity, microbial biomass, and MGEs contributed to the variation of ARGs. Finally, it was found that enhanced nutrients removal process and tertiary treatment would benefit ARGs removal.

Constrained Versus Free Cholesterol in DPPC Membranes: A Comparison of Chain Ordering Ability Using Deuterium NMR.

We report here the first exploration of the nature of the hydrophobic region of bilayer membranes formed from sterol-modified phospholipids [Huang, Z.; Szoka, F. C., Sterol-Modified Phospholipids: Cholesterol and Phospholipid Chimeras with Improved Biomembrane Properties. J. Am. Chem. Soc. 2008, 130 (46), 15702-15712] & [Ding, J.; Starling, A. P.; East, J. M.; Lee, A. G., Binding Sites for Cholesterol on Ca(2+)-ATPase Studied by Using a Cholesterol-Containing Phospholipid. Biochemistry 1994, 33 (16), 4974-4979]. Using 2H NMR spectroscopy, we present our results for the phase behavior and acyl chain ordering of multilamellar vesicles (MLVs) of a sterol-modified phospholipid, 1-cholesterylhemisuccinoyl-2-palmitoyl(d31)-sn-glycero-3-phosphocholine (hereafter referred to as CholPPC-d31). We compared our results with the conformational order induced by cholesterol at various concentrations in 1-palmitoyl,2-palmitoyl(d31)-sn-glycero-3-phosphocholine (DPPC-d31)/cholesterol membranes. On the basis of the existing literature [Foglia, F.; Barlow, D. J.; Szoka, F. C.; Huang, Z.; Rogers, S. E.; Lawrence, M. J., Structural Studies of the Monolayers and Bilayers Formed by a Novel Cholesterol-Phospholipid Chimera. Langmuir 2011, 27 (13), 8275-8281], we expected to find that the deuterated palmitoyl chain in CholPPC-d31 membranes had an order parameter profile similar to the deuterated palmitoyl chain of sn-2 labeled DPPC-d31 in MLVs of a mixture of DPPC-d31 with 40 mol % unconstrained cholesterol. Our data indicate that the ordering ability of cholesterol in CholPPC is significantly reduced compared to free cholesterol in DPPC. This result emphasizes that cholesterol molecules must be free to move in the bilayers to reach their maximum ordering ability. In other words, when compared to unconstrained cholesterol, the constrained cholesterol moiety in CholPPC causes nonoptimal chain packing.

Biodistribution and In Vivo Antileishmanial Activity of 1,2-Distigmasterylhemisuccinoyl-sn-Glycero-3-Phosphocholine Liposome-Intercalated Amphotericin B.

1,2-Distigmasterylhemisuccinoyl-sn-glycero-3-phosphocholine (DSHemsPC) is a new lipid in which two molecules of stigmasterol (an inexpensive plant sterol) are covalently linked via a succinic acid to glycerophosphocholine. Our previous study revealed that liposome (Lip)-intercalated amphotericin B (AMB) prepared from DSHemsPC (DSHemsPC-AMB-Lip) possesses excellent colloidal properties and in vitro antifungal and antileishmanial activities similar to those of the liposomal AMB preparation AmBisome. The aim of this study was to determine the biodistribution and evaluate the antileishmanial effects of DSHemsPC-AMB-Lip in Leishmania major-infected BALB/c mice. The serum profile and tissue concentrations of AMB were similar in DSHemsPC-AMB-Lip- and AmBisome-treated mice after intravenous (i.v.) injection. Multiple i.v. doses of the micellar formulation of AMB (Fungizone; 1 mg/kg of body weight), DSHemsPC-AMB-Lip (5 mg/kg), and AmBisome (5 mg/kg) were used in L. major-infected BALB/c mouse models of early and established lesions. In a model of the early lesions of cutaneous leishmaniasis (CL), the results indicated that the level of footpad inflammation was significantly (P < 0.001) lower in mice treated with DSHemsPC-AMB-Lip and AmBisome than mice treated with empty liposomes or 5% dextrose. The splenic and footpad parasite load was also significantly (P < 0.001) lower in these groups of mice than in control mice that received 5% DW or free liposome. The in vivo activity of DSHemsPC-AMB-Lip was comparable to that of AmBisome, and both provided improved results compared to those achieved with Fungizone at the designated doses. The results suggest that systemic DSHemsPC-AMB-Lip administration may be useful for the treatment of leishmaniasis, and because it costs less to produce DSHemsPC-AMB-Lip than AmBisome, DSHemsPC-AMB-Lip merits further investigation.