Loaded Lipid Nanocarriers Research Articles

Telmisartan loaded lipid nanocarrier as a potential repurposing approach to treat glioma: characterization, apoptosis evaluation in U87MG cells, pharmacokinetic and molecular simulation study

The study explores anticancer potential of telmisartan (TS) loaded lipid nanocarriers (TLNs) in glioma cells as a potential repurposing nanomodality along with estimation of drug availability at rat brain. Experimental TLNs were produced by previously reported method and characterized. In vitro anticancer efficacy of experimental TLNs was estimated by MTT, confocal microscopy, and FACs analysis in glioma cells. Plasma and brain pharmacokinetic (PK) parameters were also analysed by LCMS/MS. Spherical, nanosized, homogenous, unilamellar, TLNs were reported having desirable drug loading (9.5% ± 0.6%), negative zeta potential and sustained TS release tendency. FITC-TLNs were sufficiently internalized into U87MG cells line within 0.5 h incubation period. IC50 for TLNs was considerably higher than free TS in the tested glioma cell lines. Further, TLNs induced superior apoptotic effect in U87MG cells than TS. PK (plasma/brain) data depicted higher AUC, V ss, MRT with lower Clt for TLNs suggesting improved bioavailability, in vivo residence and sustained drug availability than free TS administration. Docking studies rationalized in vitro/in vivo results as preferably higher binding affinity (docking score:12.4) was detected for TS with glioma proteins. Further, in vivo studies in glioma bearing xenograft model is underway for futuristic clinical validation of TLNs.

Quality by design (QbD) commended exploration of bosutinib loaded lipid nanocarriers for food effect attenuation and bioavailability enhancement in breast cancer

Bosutinib (BOS), a BCS class IV drug suffers from poor aqueous solubility and bioavailability along with significant food effect. Lipid nanocarriers (LNC) have the potential to circumvent bioavailability related issues associated with hydrophobic moieties. In this endeavor, we explore the potential of novel lipid nanocarriers to circumvent the bioavailability pitfalls, while minimizing food effect and pharmacokinetic variability. Quality by design and multi-variate analysis was adopted for the optimization of various process parameters during nanoparticle fabrication. The optimized particle size, polydispersity index (PDI) and zeta potential were found to be 131.7 nm, 0.105 and −9.29 mV respectively. Ex vivo studies revealed improved intestinal permeation of LNC. Enhancements in cytotoxicity, ROS generation and apoptosis were observed against MCF-7 cells that could be attributed to elevated intracellular drug accumulation using LNC. Pharmacokinetic studies revealed a 2.6-fold increase in the bioavailability of BOS during fasted state and a 1.36-fold increase during fed state when BOS was administered via LNC, indicating superior oral bioavailability. Cmax fast/fed was found to be 0.94 while, AUC fast/fed was 0.9258 which was close to 1, indicating attenuation of the food effect by BOS LNC. Therefore, LNCs can serve as promising delivery carriers for attenuation of food effect during breast cancer therapy.

Development and Validation of RP-HPLC Method for Quantification of Total, Free and Entrapped Ritonavir in Lipid Nanocarriers and Drug content of Film Coated Fixed Dose Formulation

Abstract: Aim: The current study was aimed to develop and validate a simple isocratic, precise, sensitive, accurate and robust reverse phase HPLC analytical method for the quantification of total, free and entrapped ritonavir in lipid nanocarriers and drug content of the film-coated fixed-dose formulation. Materials and Methods: The method was developed by using Inertsil ODS-3V C18 column as stationary phase, orthophosphoric acid (OPA) in water (pH 3.0) and acetonitrile as mobile phase. Further, the method was validated following ICH Q2(R1) guidelines. Ritonavir loaded lipid nanocarriers were developed using hot-emulsion and probe-sonication method. A solid phase extraction (SPE) method was developed for the separation of free and entrapped ritonavir. Total ritonavir was extracted from lipid nanocarriers (LNCs) and film-coated tablets using methanol and analyzed with validated method. Results: The responses were found to be linear and precise over a range of 0.25 μg/mL to 16 μg/mL. The limit of detection (LOD) and limit of quantification (LOQ) of the RP-HPLC method were found to be 14.06 ng/mL and 42.60 ng/mL, respectively which emphasizes the sensitivity of the method. The recovery of ritonavir from LNCs was found to be within 3% of the total drug present in LNCs. Similar, amount of drug recovery was found from assay of marketed formulation i.e., > 97%. Conclusion: The SPE method is capable of separating free and entrapped ritonavir from LNCs. The developed HPLC method is sensitive, robust, economical and gives high recovery. The developed HPLC method can also be employed for routine quantitative analysis of ritonavir in bulk formulation. Key words: HPLC method, Ritonavir, Validation, SPE, NLC, Bulk formulation.

Mechanistic evaluation of lymphatic targeting efficiency of Atazanavir sulfate loaded lipid nanocarriers: In-vitro and in-vivo studies

In the present study, Atazanavir sulfate-loaded solid lipid nanoparticles (ATZ-SLNs) were developed and characterized for oral bioavailability enhancement and lymphatic absorption. ATZ-SLNs were formulated by emulsion-solvent evaporation technique using hydrogenated castor oil and sodium oleate. The optimized formulation had a mean particle size of 190.1 ± 2.45 nm, the zeta potential of −42.63 ± 2.46 mV and entrapment efficiency of 94.26 ± 2.12%. Transmission electron microscopy and Field emission-scanning electron microscopy morphology indicated discrete and round structures without aggregation. In-vitro drug release study showed controlled drug release of 80.36% in 12 h in simulated intestinal fluid. Cell-line study in Caco-2 cells showed increased permeability upon SLN formulation and mode of cellular uptake of SLN as clathrin and caveoli mediated endocytosis. In-vivo pharmacokinetic study in rats indicated increased oral bioavailability using ATZ-SLNs by 200% compared to suspension formulation. A lymphatic transport study revealed that SLNs were transported via lymphatic vessels. In organ biodistribution study, peyer's patch region showed a 4.5 fold higher uptake of ATZ through ATZ-SLNs formulation than non-peyer's patch region and high accumulation in spleen and brain. This delivery approach could maximize the drug concentrations to the lymphatic system leading to effective therapy for HIV.

Bioactive Loaded Lipid-based Nanostructures: A Novel Insight for Age-related Neurodegeneration.

Substantial affirmation suggested that oxidative stress remains an impelling target, contributing to initiate and exacerbate the multiple neurological complications in age-related neurodegeneration (ARN). Factors including gene and environmental toxins are now becoming the most threatening cause of oxidative stress, which leads to mitochondrial dysfunction of the neurons that ultimately causes permanent loss of their functionality. Clinical trials on antioxidants are still in the pipeline to access them as a potential therapeutic class. But this raised the generosity for not only to investigate the module of the antioxidant mechanism but also to justify the drug delivery and dose regimen. Biological barriers, predominantly, Blood-brain barrier (BBB) and rapid firstpass metabolism, are some of the potential obstacles for the effective targeting of the therapeutic agent. Bioactive drugs with antioxidant capacity, loaded with lipid-based Nano career system have revealed to be a novel therapeutic intervention for ARN. The review will deal with the comprehensive state-of-art methodology for the delivery of bioactive loaded lipid Nanocarriers to treat neurodegeneration. A systematic analysis of published reports will help the researchers to understand the role of natural compound loaded Nanoengineered system in the field of ARN as a potential Nano therapeutic intervention.

Influence of carrier oil on the physical stability and in vitro digestion of vitamin K lipid nanocarriers

The present study aimed to investigate the physical stability and in vitro digestion of vitamin K loaded lipid nanocarriers with different carrier oils. The incorporated vitamin K in nanocarriers was determined by the HPLC. The diameters of nanocarriers were 102.3–119.6 nm, and PDI and zeta-potential were lower than 0.3 and −40 mV, respectively, which means a stable dispersion system. The physical stability after heat, freeze (−18 °C) thaw, and salt treatments were maintained, but the size and PDI of nanocarriers with soybean oil significantly increased after freeze (−70 °C) thaw treatment. The destabilization of the dispersion by creaming was observed by turbidimetric measurements, which revealed that the nanocarrier prepared with coconut oil showed higher stability than others. The vitamin K retention after UV irradiation was higher in nanocarriers than in ethanolic solution. Moreover, nanocarriers with coconut oil were digested faster than others, due to their lower unsaturation degree and shorter chain length.

Topical creams of piperine loaded lipid nanocarriers for management of atopic dermatitis: development, characterization, and in vivo investigation using BALB/c mice model

The aim of the research work was to investigate the efficacy of cream loaded with lipid nanocarriers (ethosomes) of piperine for the management of atopic dermatitis (AD) in comparison to conventional cream. Ethosomes of piperine were formulated with varying concentration of phosphatidylcholine and ethanol; and evaluated for entrapment efficiency (EE), sedimentation behaviour, vesicle size, zeta potential, in vitro drug release, and shape. Creams loaded with optimized ethosomal dispersion of piperine were formulated and evaluated for physicochemical parameters, ex vivo permeation and drug retention in skin layers. Similarly, conventional creams of piperine in the same concentrations were formulated and evaluated. The optimized ethosomal a conventional cream was evaluated for cytotoxicity using HaCat cell lines and in vivo on BALB/c mice model. The EE (%) and vesicle size was 74.30 ± 3.88% and 318.1 nm, respectively, for optimized ethosomal dispersion. The zeta potential was −32.6 mV and vesicles were spherical in shape. The ethosomal cream showed higher deposition in the epidermis and dermis. The creams were non-cytotoxic to HaCat cell lines. In comparison to the negative control, the ethosomal (0.1%) and conventional (0.125%) cream, both significantly decreased the ear and skin thickness, skin severity; and WBC, granulocytes, and IgE antibodies level in the BALB/c mice model. The efficacy of ethosomal cream was significantly higher than conventional cream as compared to tacrolimus (0.1%). Ethosomal cream of piperine showed good potential for the management of AD in comparison to conventional cream.

Preparation, In Vitro characterization and stability studies of ropinirole lipid nanoparticles enriched hydrogel for treatment of neurodegeneration diseases

Ropinirole (RP), is a selective dopamine agonist that is used alone or with other medications to treat the symptoms of Parkinson’s disease (PD). RP has low bioavailability of only about 50% due to the first-pass metabolism, and it requires frequent dosing during oral administration. The objective of the current research was to develop RP loaded solid lipid nanoparticles (RP-SLNs), nanostructured lipid carriers (RP-NLCs), and their corresponding hydrogels (RP-SLN-C and RP-NLC-C) that might improve efficacy in PD treatment. RP nanoparticles were prepared by homogenization aided probe sonication method and optimized based on particle size, polydispersity index (PDI), zeta potential (ZP), assay, entrapment efficiency, and in vitro release studies. Optimized formulations were converted to hydrogel formulations using Carbopol 934 as a gelling polymer and optimized based on rheological and release characteristics. Optimized formulations were further evaluated using differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), scanning electron microscopy (SEM), freeze-drying, and stability study at refrigerated and room temperatures. The optimized RP-SLN formulation showed particle size and entrapment efficiency of 213.5±3.8 nm and 77.9±3.1% compared to 190.6±3.7 nm and 85.7±1.7% for optimized RP-NLC formulation. PXRD supplemented and confirmed DSC results, RP was entrapped in a molecularly dispersed state inside the core of the lipid nanocarrier. Furthermore, RP loaded lipid nanocarriers revealed a spherical shape in SEM images. In vitro release studies demonstrated sustained release profiles for RP from SLNs, NLCs, and their hydrogels over 24 h and were stable over three months at 4ºC and 25ºC storage conditions. Keywords: Parkinson’s disease, Ropinirole, Solid lipid nanoparticles, Nanostructured lipid carriers, Hydrogel.

Resveratrol entrapped food grade lipid nanocarriers as a potential antioxidant in a mayonnaise

Resveratrol (RES) loaded lipid nanocarriers (RES-NLC) were produced using an Ultra-Turrax with high shear force using cocoa butter (CB), corn oil (CO), and. Tween 80. Particle size, morphology, % encapsulation efficiency (EE%) and physical stability for 60 days were studied. A mayonnaise was fortified with RES-NLC. The results showed the particles had a smooth and spherical structure and particle size was 71.9 nm and EE% = 82.9%. Fourier transform infrared spectroscopy and X-ray diffraction analysis showed no chemical interaction between RES and NLC components, and RES was not crystallized. The peroxide content in the sample containing RES-NLC increased slightly and antioxidant activity was higher than in other samples. In general, the use of RES as a natural antioxidant prevented the lipid oxidation in the mayonnaise during storage and NLC can be a good system for RES coating to preserve its antioxidant properties.

Azelaic acid-willow bark extract-panthenol – Loaded lipid nanocarriers improve the hydration effect and antioxidant action of cosmetic formulations

The classic medication recommended in acne and atopic dermatitis comprises the administration of antibiotics, corticosteroids and topical steroids. To overcome some inconveniences of using synthetic antibiotics, e.g. irritation, inflammation and dryness, this study proposes a biotherapeutic strategy which is based on cosmetic formulations including nanostructured lipid carriers (NLCs) loaded with three actives, azelaic acid (AzA), white willow bark extract (WBE) and panthenol (Ph). The main objective was to obtain non-cytotoxic and hemocompatible NLCs with high entrapment efficiency for all actives, controlled release of these actives and enhanced hydration effect and antioxidant action. The large confinement space of developed NLCs prepared with echium oil has been proved by the appropriate encapsulation efficiencies for AzA, WBE and Ph actives, with values reaching 90 %. The NLC-AzA-WBE- Ph improved the reconstruction of epidermal cells, the cell viability of BJ human fibroblast line being up to 100 % at concentrations up to 62.5 μg/mL. The hemolytic tests revealed the protective effect of the WBE and AzA on the red blood cells; the hemolysis has been drastic reduced, the developed NLC manifesting a nonhemolytic action. The synergism of all actives led to an efficient antioxidant NLCs that inhibits 97 % of short-life radicals and 15 % of ABTS long-life radical cations. The incorporation of NLC-AzA-WBE- -Ph into a Carbopol gel resulted in an advanced cosmetic formulation that assures a high hydration effect. The degree of hydration in the cosmetic formulations ranges up to 84 % in the T-zone for type-III skin (predisposed in acne) and above 80 % in the body region for skin type-II (susceptible in dermatitis). By summarizing, the moisturizing nature of Ph, completed by the antioxidant activity and controlled release behaviour of WBE and AzA, significant enriched the final properties of the NLCs-based cosmetic formulations for a dual use in acne and atopic dermatitis therapy.

Lipid Nanoparticle Inclusion Prevents Capsaicin-Induced TRPV1 Defunctionalization.

Background: Capsaicin (CPS) is a highly selective agonist of the transient receptor potential vanilloid type 1 (TRPV1) with a nanomolar affinity. High doses or prolonged exposure to CPS induces TRPV1 defunctionalization and, although this effect is currently used for the treatment of thermal hyperalgesia in chronic pain conditions, it is responsible of detrimental effects, such as denervation of sensory fibers. The aim of the present study was to formulate CPS loaded lipid nanocarriers (CPS-LN) in order to optimize CPS release, thus preventing TRPV1 internalization and degradation. Methods: CPS-LNs were formulated and characterized by in vitro studies. The activation of TRPV1 receptors after CPS-LN administration was evaluated by measuring spontaneous pain that was induced by local injection into the plantar surface of the mouse hind-paw. Moreover, the expression of TRPV1 in the skin was evaluated by western blot analysis in CPS-LN injected mice and then compared to a standard CPS solution (CPS-STD). Results: CPS inclusion in LN induced a lower pain response when compared to CPS-STD; further, it prevented TRPV1 down-regulation in the skin, while CPS-STD induced a significant reduction of TRPV1 expression. Conclusions: Drug encapsulation in lipid nanoparticles produced an optimization of CPS release, thus reducing mice pain behavior and avoiding the effects that are caused by TRPV1 defunctionalization related to a prolonged activation of this receptor.

Development of BSA conjugated on modified surface of quercetin- loaded lipid nanocarriers for breast cancer treatment

Multiple drug resistance is a key limitation for the clinical administration of chemotherapeutic drugs, apart from this their major limitations with free drugs are poor solubility, physiochemical and pharmaceutical behavior. These limitations with free drugs can be overcome by nanoformulations using natural biopolymer. In this study, successful utilization of P-glycoprotein receptor for the delivery of anticancer drug quercetin (Q), encapsulated inside the lipid nanocarriers (LNs) was introduced for the treatment of breast cancer. Bovine serum albumin (BSA) was conjugated on the Q-loaded LNs( BSA-Q-LNs) for targeting to receptor. Q-loaded LNs were prepared using a single emulsion solvent evaporation method, followed by surface modification of Q-loaded LNs using charge interaction. Finally, surface modified Q-loaded LNs were conjugated with BSA using thiol reaction. The formulated nano construct was a spherical structure with a shell size of 530 nm. Encapsulation of Q inside the matrix of LNs is confirmed from shift in FT-IR, XRD peak. The release kinetic of Q- loaded LNs formulation was best fitted in a first-order kinetic model suggesting early burst of Q followed by slow release. The entrapment efficiency and drug loading efficiency were found to be 76 ± 0.3% and 15.72 ± 0.7% respectively. The Q-loaded LNs and BSA-Q-LNs displayed the improved cytotoxicity in drug resistance human breast cancer cell line (MCF-7) as compared to free Q.

Synergism of essential oils with lipid based nanocarriers: emerging trends in preservation of grains and related food products

Abstract Grains are one of the major food staples in the world. The cereal grains are easily susceptible to damage by moisture content, flour beetles and food pathogens during storage, harvesting and post harvesting. Food preservative techniques namely drying, freezing, and dehydration, acquire little advantages. However, they cause few undesirable alterations in the organoleptic and nutritional properties of the preserved food items. Therefore, there is a continuous search for new preservation techniques in food industries, to satisfy the customer demands on the addition of natural food preservatives, devoid of pathogenic contaminants and without changes in organoleptic properties. Essential oils (EOs) have been predicted as “natural food additives” in the preservative process. The synergistic potential of EOs with various nanocarriers plays an emerging role in the food industry. Therefore, the present review has focused on the lipid based nanocarriers, and the methods used for the functionalization or encapsulation of EOs and applications in the preservation of food items such as cooked rice, rice flour, grains, sliced breads have also been discussed. The present review ascertains the antimicrobial significance of active EOs loaded lipid nanocarriers in the form of nano emulsions, solid lipid nanoparticles and liposomes for preserving grains and flours.

Superparamagnetic Iron Oxide–Loaded Lipid Nanocarriers Incorporated in Thermosensitive In Situ Gel for Magnetic Brain Targeting of Clonazepam

The objective of the study was to target clonazepam to the brain through the intranasal olfactory mucosa using nanolipid carriers loaded with superparamagnetic iron oxide nanoparticles (SPIONs) to allow nanocarrier guidance and retention with an external magnetic field. For improved delivery, the nanolipid carriers were incorporated in a thermosensitive mucoadhesive in situ gel. Different nanolipid carriers including solid lipid nanoparticles and nanostructured lipid carriers (NLC) were prepared and characterized with respect to particle size, zeta potential, entrapment efficiency, and in vitro release. The NLC composed of 3 solid lipids (Compritol® 888, stearic acid, and glyceryl monostearate) and 2 liquid oils (oleic acid and glyceryl monooleate) showed the most satisfactory characteristics and was loaded with SPION (NLC/SPION). Both formulae (NLC and NLC/SPION) were incorporated in an optimized thermosensitive mucoadhesive in situ system composed of 15% pluronic 127 and 0.75% sodium alginate and evaluated for the anticonvulsant action in chemically induced convulsive Swiss Albino mice. The treatment of animals with NLC/SPION significantly prolonged the onset times for convulsion and considerably protected the animals from death. One can thus hope for the emergence of a new intranasal treatment of epilepsy with consequent decrease in peripheral side effects of clonazepam.

Resveratrol-Loaded Lipid Nanocarriers: Correlation between In Vitro Occlusion Factor and In Vivo Skin Hydrating Effect.

Lipid nanocarriers show occlusive properties that may be related to their ability to improve skin hydration. The aim of this work was to evaluate the relationship between in vitro occlusion factor and in vivo skin hydration for three types of lipid nanocarriers: nanoemulsions (NEs), solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). These lipid nanocarriers were loaded with trans-resveratrol (RSV) and incorporated in gel vehicles. In vitro occlusion factor was in the order SLNs > NLCs > NEs. Gels containing unloaded or RSV loaded lipid nanocarriers were applied on the back of a hand of 12 healthy volunteers twice a day for one week, recording skin hydration changes using the instrument Soft Plus. An increase of skin hydration was observed for all lipid nanocarriers (SLNs > NLCs > NEs). RSV loading into these nanocarriers did not affect in vitro and in vivo lipid nanocarriers effects. A linear relationship (r2 = 0.969) was observed between occlusion factor and in vivo increase of skin hydration. Therefore, the results of this study showed the feasibility of using the occlusion factor to predict in vivo skin hydration resulting from topical application of different lipid nanocarriers loading an active ingredient with no inherent hydrating activity.

Influence of sonophoresis on transdermal drug delivery of hydrophilic compound-loaded lipid nanocarriers

The effect of sonophoresis on the transdermal drug delivery of sodium fluorescein (NaFI)-loaded lipid nanocarriers such as liposomes (LI), niosomes (NI) and solid lipid nanoparticles (SLN) was investigated by confocal laser scanning microscopy (CLSM), fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The results showed that SN decreased the skin penetration of NaFI-loaded SLN (6.32-fold) and NI (1.79-fold), while it increased the penetration of NaFI-loaded LI (5.36-fold). CLSM images showed the red fluorescence of the LI and NI bilayer on the superficial layer of the stratum corneum. However, the red fluorescent probe of the SLN was not visualized in the skin. FTIR results of the LI and NI with SN showed no effect on lipid stratum corneum ordering, suggesting that the fragment of bilayer vesicles might repair the damaged skin. For SLN, the strengthening of stratum corneum by covering the disrupted skin with solid lipids was shown. SEM images show disrupted carriers of all the formulations adsorbed onto the damaged skin. In conclusion, the SN changed the properties of both the skin surface and lipid nanocarrier, demonstrating that disrupted skin might be repaired by a disrupted nanocarrier.

Brain delivery of baclofen as a hydrophilic drug by nanolipid carriers: Characteristics and pharmacokinetics evaluation

Formulation of baclofen in lipid-based nanoparticles may be helpful to overcome its difficulties in order to reach the site of action in the CNS. This study reports production, characterization and pharmacokinetics evaluation of baclofen loaded lipid nano-carriers. Lipid nano-carriers containing baclofen were prepared by using double emulsion solvent evaporation method and physicochemical characteristics of prepared nanoparticles were evaluated. The selected formulation was administered on rat model to be compared with an aqueous drug solution. Plasma and brain concentrations of drug and pharmacokinetics parameters were compared. Nanostructured lipid carriers (NLC) formulation showed better physicochemical properties than solid lipid nanoparticles (SLNs). Also, the formulation of baclofen by NLC increased the half-life of drug in plasma and brain up to 10 and 1.5 times respectively compared to the solution formulation. Results revealed a more significant and prolonged effect of baclofen-NLC in comparison with baclofen solution in both plasma and brain mediums that emphasize and prove theories on the formulation of hydrophilic drug in NLCs can be a solution for target drug delivery to the brain.

Folic acid loaded lipid nanocarriers with promoted skin antiaging and antioxidant efficacy

Ageing is the progressive deterioration of physiological functions in organisms. Folic acid (FA) can be used as antiaging. The objective of this research is the feasibility of topical delivery of FA using nanostructured lipid carriers (NLCs) to offer sustained antioxidant and antiaging effects. FA NLCS were prepared by hot high pressure homogenization. Encapsulation efficiency (EE), in vitro release, ex vivo permeation and skin targeting were evaluated. Characterization of selected formulations was assessed, together with stability and water occlusion. Further, histology and antioxidant potential were evaluated. EE exceeded 95%. Formulations with 30% oil showed maximum skin targeting, water occlusion and high efficiency of hydration and antioxidant potential. Incorporation of oil into solid lipids causes more imperfections in the crystal lattice, providing high drug encapsulation. The small particle size leads to forming a depot in the skin providing efficient skin targeting, water occlusion, antiaging and antioxidant effects especially for the 30% oil containing formula; F11. The results emphasize the success of topical application of FA NLCs. F11 represents a promising, stable preparation, achieving remarkable long acting skin hydration, in vitro and ex vivo antioxidant potential lasting for >4 days.

Simvastatin nanolipid carriers decreased hypercholesterolemia induced cholesterol inclusion and phosphatidylserine exposure on human erythrocytes

This study aimed to develop simvastatin (SV) loaded lipid nanocarriers as solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) and lipid nanoemulsion (LNE) and to estimate their in vitro erythrocyte uptake to reduce the cholesterol level. Therefore, numerous SLNs were prepared using Imwitor 900K, Stearic acid, Softisan 154 and Dynasan 118. For NLC, 30% w/v of Miglyol 812 was added to the previous lipids and LNE consisting 100% w/v of Miglyol 812 was also prepared for comparison. These lipid nanocarriers exhibited spherical-shapes with negative charges and particle size lower than 400nm (PDI<0.3). Moreover, the optimized formulations were LNE (Miglyol 812), NLC (Stearic acid and Miglyol 812) and SLN (Stearic acid), which showed the highest entrapment efficiency and drug release. In addition, the percent of erythrocyte uptake of SV from free SV solution, optimized SLN, NLC and LNE was 28%, 78%, 85% and 72%, respectively. Furthermore, incubation of erythrocytes with cholesterol enriched plasma resulted in a significant increase in the percent of cholesterol inclusion, hemolysis and eryptosis compared to control. In contrast, the incubation of erythrocytes with cholesterol rich plasma in the presence of the optimized nanocarriers resulted in a significant decrease percent of cholesterol inclusion, hemolysis and eryptosis. However, effect of the lipid nanocarriers on the measured parameters was more pronounced than that of the free drug. Thus, these results suggested that the lipid nanocarriers might be a promising nanocarrier for SV to maintain the native erythrocyte function in hypercholesterolemia.

Sodium colistimethate loaded lipid nanocarriers for the treatment of Pseudomonas aeruginosa infections associated with cystic fibrosis

Lung impairment is the most life-threatening factor for cystic fibrosis patients. Indeed, Pseudomonas aeruginosa is the main pathogen in the pulmonary infection of these patients. In this work, we developed sodium colistimethate loaded lipid nanoparticles, namely, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), as a strategy to enhance the antimicrobial therapy against P. aeruginosa in cystic fibrosis patients. The nanoparticles obtained displayed a 200–400nm size, high drug entrapment (79–94%) and a sustained drug release profile. Moreover, both SLN and NLC presented antimicrobial activity against clinically isolated P. aeruginosa. The integrity of the nanoparticles was not affected by nebulization through a mesh vibrating nebulizer. Moreover, lipid nanoparticles appeared to be less toxic than free sodium colistimethate in cell culture. Finally, an in vivo distribution experiment showed that nanoparticles spread homogenously through the lung and there was no migration of lipid nanoparticles to other organs, such as liver, spleen or kidneys.