Prevention of chemotherapy-related bone loss with doxorubicin-loaded solid lipid nanoparticles.

Aim: Breast cancer and its metastases involve high mortality even with advances in chemotherapy. Solid lipid nanoparticles provide a platform for drug delivery, reducing side effects and treatment-induced bone loss. A solid nanoparticle containing doxorubicin was evaluated for its ability to prevent bone loss in a pre-clinical breast cancer model. Methods: We investigated the effects of SLNDox in an aggressive metastatic stage IV breast cancer model, which has some important features that are interesting for bone loss investigation. This study evaluates bone loss prevention potential from solid lipid nanoparticles containing doxorubicin breast cancer treatment, an evaluation of the attenuation of morphological changes in bone tissue caused by the treatment and the disease and an assessment of bone loss imaging using computed tomography and electron microscopy. Results: Chemotherapy-induced bone loss was also observed in tumor-free animals; a solid lipid nanoparticle containing doxorubicin prevented damage to the growth plate and to compact and cancellous bones in the femur of tumor-bearing and healthy animals. Conclusion: The association of solid lipid nanoparticles with chemotherapeutic drugs with proven efficacy promotes the prevention of serious consequences of chemotherapy, reducing tumor progression, increasing quality of life and improving prognosis and survival.

[Box: see text].

Formulation Optimization and Characterization of Solid Lipid Nanoparticles of Apixaban.

BACKGROUND: Unpredictable situations such as clotting of blood, deep vein thrombosis, and pulmonary embolism arise in the body, which is the leading cause of mortality. Such conditions generally arise after surgery as well as after treatment with oral anticoagulant agents. Apixaban is a novel oral anticoagulant widely recommended for the prevention and treatment of strokes and blood clots suffering from nonvalvular atrial fibrillation by suppressing factor Xa. Apixaban has a log P of 2.71 with poor solubility and reported maximum bioavailability of approximately 50%. OBJECTIVE: Hence, the current research mainly focused on the improvement of solubility, bioavailability, and therapeutic efficacy of Apixaban via solid lipid nanoparticles (SLN). METHODS: The SLN was developed using the hot-homogenization method using a high-pressure homogenizer. The drug-lipid compatibility study was assessed by the FTIR, and the thermal analysis was performed using differential scanning calorimetry (DSC). During the scrutiny of lipids, the highest solubility of Apixaban was estimated in the glyceryl monostearate, hence selected for the formulation. Moreover, the colloidal solution was stabilized by the polyethylene glycol 200. The Design of Expert software (Version 13, Stat-Ease) was implemented for the optimization analysis by considering the 3-independent factors and 2-dependent parameters. The Patents on the SLN are Indian 202321053691, U.S. Patent, 10,973,798B2, U.S. Patent, U.S. Patent 2021/0069121A1, U.S. Patent 2022/0151945A1. RESULTS: Box-Behnken design was applied along with ANOVA, which showed a p-value less than 0.05 for the dependent parameters such as particle size and entrapment efficiency (p-value: 0.0476 and 0.0379). The optimized batch F10 showed a particle size of 167.1 nm, -19.5 mV zeta potential, and an entrapment efficiency of 87.32%. The optimized batch F10 was lyophilized and analyzed by Scanning electron microscopy (SEM), which showed a particle size of 130 nm. The solid powder was filled into the capsule for oral delivery. CONCLUSION: The marked improvement in solubility and bioavailability was achieved with F10- loaded Apixaban via Solid lipid nanoparticles. Moreover, the sustained released profile also minimizes the unseen complications that occur due to the clotting of blood.

Nanoparticles and Their Applications in Lipid Signaling.

This chapter provides an overview of the diverse range of applications associated with nanoparticles. The application of nanoparticles in the medical field has garnered considerable attention due to their unique properties and versatile compositions. They have shown promise in the treatment of cancer, fungal and viral infections, and pain management. These systems provide numerous benefits, such as increased drug stability, improved bioavailability, and targeted delivery to specific tissues or cells. The objective of this chapter is to provide a brief analysis of the differences between nanoparticles and lipid particles, focusing particularly on the importance of nanoparticle size and composition in their interactions with lipids. Additionally, the applications of nanoparticles in lipid signaling will be discussed, considering the vital roles lipids play in cellular signaling pathways. Nanoparticles have shown immense potential in the regulation and control of medical pathways. In this case, we will focus on the manufacture of liposomes, a type of nanoparticle composed of lipids. The reason behind the extensive investigation into liposomes as drug delivery vehicles is their remarkable biocompatibility and adaptability. This section will provide insights into the methods and techniques employed for liposome formulation.

Functionalized solid lipid nanoparticles combining docetaxel and erlotinib synergize the anticancer efficacy against triple-negative breast cancer.

The goal of the study was to fabricate folic acid functionalized docetaxel (DOC)/erlotinib (ERL)-loaded solid lipid nanoparticles (SLNs) to synergistically increase the anticancer activity against triple-negative breast cancer. DOC/ERL-SLNs were prepared by the high shear homogenization - ultrasound dispersion method (0.1 % w/v for DOC, and 0.3 %w/v for ERL) and optimized using Plackett Burman Design (PBD) followed by Box Behnken Design (BBD). The optimized SLNs demonstrated particle size < 200 nm, PDI < 0.35, and negative zeta potential with entrapment and loading efficiency of ∼80 and ∼4 %, respectively. The SLNs and folic acid functionalized SLNs (FA-SLNs) showed sustained release for both drugs, followed by Higuchi and Korsemeyer-Peppas drug release models, respectively. Further, the in vitro pH-stat lipolysis model demonstrated an approximately 3-fold increase in the bioaccessibility of drugs from SLNs compared to suspension. The TEM images revealed the spherical morphology of the SLNs. DOC/ERL loaded SLNs showed dose- and time-dependent cytotoxicity and exhibited a synergism at a molar ratio of 1:3 in TNBC with a combination index of 0.35 and 0.37, respectively. FA-DOC/ERL-SLNs showed enhanced anticancer activity as evidenced by MMP and ROS assay and further inhibited the colony-forming ability and the migration capacity of TNBC cells. Conclusively, the study has shown that SLNs are encouraging systems to improve the pharmaceutical attributes of poorly bioavailable drugs.

Optimization of atorvastatin and quercetin-loaded solid lipid nanoparticles using Box-Behnken design.

Aim: The study explores the synergistic potential of atorvastatin (ATR) and quercetin (QUER)- loaded solid lipid nanoparticles (SLN) in combating breast cancer. Materials & methods: SLNs were synthesized using a high-shear homogenization method and optimized using Box-Behnken design. The SLNs were characterized and evaluated for their in vitro anticancer activity. Results: The optimized SLN exhibited narrow size distribution (PDI = 0.338 ± 0.034), a particle size of 72.5 ± 6.5 nm, higher entrapment efficiency (<90%), sustained release and spherical surface particles. The in vitro cytotoxicity studies showed a significant reduction in IC50 values on MDA-MB-231 cell lines. Conclusion: We report a novel strategy of repurposing well-known drugs and encapsulating them into SLNs as a promising drug-delivery system against breast cancer.

[Box: see text].

Solid Lipid Nanoparticles Loaded with Dexamethasone Palmitate for Pulmonary Inflammation Treatment by Nebulization Approach.

Pneumonia stands as the leading infectious cause of childhood mortality annually, underscoring its significant impact on pediatric health. Although dexamethasone (DXMS) is effective for treating pulmonary inflammation, its therapeutic potential is compromised by systemic side effects and suboptimal carrier systems. To address this issue, the current study introduces solid lipid nanoparticles encapsulating hydrophobic dexamethasone palmitate (DXMS-Pal-SLNs) as an anti-inflammatory nanoplatform to treat pneumonia. The specialized nanoparticle formulation is characterized by high drug loading efficiency, low drug leakage and excellent colloidal stability in particular during nebulization and is proficiently designed to target alveolar macrophages in deep lung regions via local delivery with the nebulization administration. In vitro analyses revealed substantial reductions in the secretions of tumor necrosis factor-α and interleukin-6 from alveolar macrophages, highlighting the potential efficacy of DXMS-Pal-SLNs in alleviating pneumonia-related inflammation. Similarly, in vivo experiments showed a significant reduction in the levels of these cytokines in the lungs of mice experiencing lipopolysaccharide-induced pulmonary inflammation after the administration of DXMS-Pal-SLNs via nebulization. Furthermore, the study demonstrated that DXMS-Pal-SLNs effectively control acute infections without causing pulmonary infiltration or excessive recruitment of immunocytes in lung tissues. These findings highlight the potential of nebulized DXMS-Pal-SLNs as a promising therapeutic strategy for mitigating pneumonia-related inflammations.

SLN and chitosan nano-delivery systems for antibacterial effect of black seed (Nigella sativa) oil against S. aureus.

Staphylococcus aureus with current universal importance represents a main carrier of emerging antimicrobial resistance determinatives of global health concerns that have developed drug resistance mechanisms to the various available antibiotics. On the other hand, due to the antimicrobial potential of Nigella Sativa oil (NSO), it was hypothesized that incorporation of nano-carriers (NS-SLN and NS-chitosan (CH) nanoparticles) can enhance its antibacterial effects. This study evaluated the physico-chemical and antibacterial characteristics of NS-SLN and NS-CH. TEM images revealed a round shape with clear edges for both nanoparticles, and the average sizes were reported to be 196.4 and 446.6 nm for NS-SLN and NS-CH, respectively. The zeta potential and encapsulation efficiency were -28.9 and 59.4 mV and 73.22% and 88% for NS-SLN and NS-CH, respectively. The Minimum Inhibitory Concentrations for NSO, NS-SLN, and NS-CH against S. aureus were 480, 200, and 80 µg/mL, respectively. The results confirm significantly stronger antibacterial influences of NSO when loaded into chitosan nanoparticles as a potential candidate for nano-delivery of antimicrobial agents.

Enhanced Skin Penetration and Efficacy: First and Second Generation Lipoidal Nanocarriers in Skin Cancer Therapy.

Skin carcinoma remains one of the most widespread forms of cancer, and its global impact continues to increase. Basal cell carcinoma, melanoma, and squamous cell carcinoma are three kinds of cutaneous carcinomas depending upon occurrence and severity. The invasive nature of skin cancer, the limited effectiveness of current therapy techniques, and constraints to efficient systems for drug delivery are difficulties linked with the treatment of skin carcinoma. In the present era, the delivery of drugs has found a new and exciting horizon in the realm of nanotechnology, which presents inventive solutions to the problems posed by traditional therapeutic procedures for skin cancer management. Lipid-based nanocarriers like solid lipid nanoparticles and nanostructured lipid carriers have attracted a substantial focus in recent years owing to their capability to improve the drug's site-specific delivery, enhancing systemic availability, and thus its effectiveness. Due to their distinct structural and functional characteristics, these nanocarriers can deliver a range of medications, such as peptides, nucleic acids, and chemotherapeutics, via different biological barriers, such as the skin. In this review, an effort was made to present the mechanism of lipid nanocarrier permeation via cancerous skin. In addition, recent research advances in lipid nanocarriers have also been discussed with the help of in vitro cell lines and preclinical studies. Being a nano size, their limitations and toxicity aspects in living systems have also been elaborated.

Evaluation of Gemcitabine and Epigallocatechin-3-Gallate Loaded Solid Lipid Nanoparticles on Benzopyrene Induced Lung Cancer Model Via Intranasal Route: Improved Pharmacokinetics and Safety Profile.

The objective of this study was to create a new treatment for lung cancer using solid lipid nanoparticles (SLNs) loaded with gemcitabine (GEM) and epigallocatechin-3-gallate (EGCG) that can be administered through the nose. We analyzed the formulation for its effectiveness in terms of micromeritics, drug release, and anti-cancer activity in the benzopyrene-induced Swiss albino mice lung cancer model. We also assessed the pharmacokinetics, biodistribution, biocompatibility, and hemocompatibility of GEM-EGCG SLNs. The GEM-EGCG SLNs had an average particle size of 93.54 ± 11.02 nm, a polydispersity index of 0.146 ± 0.05, and a zeta potential of -34.7 ± 0.4 mV. The entrapment efficiency of GEM and EGCG was 93.39 ± 4.2% and 89.49 ± 5.1%, respectively, with a sustained release profile for both drugs. GEM-EGCG SLNs had better pharmacokinetics than other treatments, and a high drug targeting index value of 17.605 for GEM and 2.118 for EGCG, indicating their effectiveness in targeting the lungs. Blank SLNs showed no pathological lesions in the liver, kidney, and nasal region validating the safety of SLNs. GEM-EGCG SLNs also showed fewer pathological lesions than other treatments and a lower hemolysis rate of 1.62 ± 0.10%. These results suggest that GEM-EGCG SLNs could effectively treat lung cancer.

A Physiochemical, In Vitro, and In Vivo Comparative Analysis of Verteporfin-Lipid Conjugate Formulations: Solid Lipid Nanoparticles and Liposomes.

VisudyneⓇ, a liposomal formulation of verteporfin (benzoporphyrin derivative; BPD), is the only nanomedicine approved to date for photodynamic therapy (PDT). We have previously demonstrated that BPD conjugated to the lysophospholipid 1-arachidoyl-2-hydroxy-sn-glycero-3-phosphocholine (BPD-PC) exhibits the greatest physical stability in liposomes, while maintaining cancer cell phototoxicity, from a panel of BPD lipid conjugates evaluated. In this study, we prepared 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)-based solid lipid nanoparticles (LNPs) that stably entrap BPD-PC, which resemble the composition of the SpikevaxⓇ Moderna COVID-19 vaccine, and compared them to a DPPC based liposomal formulation (Lipo BPD-PC). We evaluated the photochemical, optical, and phototherapeutic properties of both formulations. We also investigated the in vivo distribution and tumor microdistribution of both formulations. Our results demonstrated that Lipo BPD-PC is able to generate 17% more singlet oxygen than LNP BPD-PC, while interestingly, LNP BPD-PC is able to produce 76% more hydroxyl radicals and/or peroxynitrite anion. Importantly, only 28% of BPD-PC leaches out of the LNP BPD-PC formulation during 7 days of incubation in serum at 37 °C, while 100% of BPD-PC leaches out of the Lipo BPD-PC formulation under the same conditions. Despite these differences, there was no significant difference in cellular uptake of BPD-PC or phototoxicity in CT1BA5 murine pancreatic cancer cells (derived from a genetically engineered mouse model). Interestingly, PDT using LNP BPD-PC was more efficient at inducing immunogenic cell death (calreticulin membrane translocation) than Lipo BPD-PC when using IC25 and IC50 PDT doses. In vivo studies revealed that CT1BA5 tumor fluorescence signals from BPD-PC were 2.41-fold higher with Lipo BPD-PC than with LNP BPD-PC; however, no significant difference was observed in tumor tissue selectivity or tumor penetration. As such, we present LNP BPD-PC as a unique and more stable nanoplatform to carry BPD lipid conjugates, such as BPD-PC, with a potential for future photodynamic immune priming studies and multiagent drug delivery.

Combination of Etoposide and quercetin-loaded solid lipid nanoparticles Potentiates apoptotic effects on MDA-MB-231 breast cancer cells.

Background: Breast cancer is a major global cancer, for which radiation and chemotherapy are the main treatments. Natural remedies are being studied to reduce the side effects. Etoposide (ETO), a chemo-drug, and quercetin (QC), a phytochemical, are considered potential factors for adaptation to conventional treatments. Objectives: The anticancer effect of the synergy between ETO and Quercetin-loaded solid lipid nanoparticles (QC-SLNs), was investigated in MDA-MB-231 cells. Methods: We developed QC-SLNs for efficient cellular delivery, characterizing their morphology, particle size, and zeta potential. We assessed the cytotoxicity of QC-SLNs and ETO on breast cancer cells via the MTT assay. Effects on apoptosis intensity in MDA-MB-231 cells have been detected utilizing annexin V-FITC, PI, and caspase activities. Real-time PCR assessed Bax gene and Bcl-2 gene fold change expression, while Western blot analysis determined p53 and p21 protein levels. Results: Spherical, negatively charged QC-SLNs, when combined with ETO, significantly enhanced inhibition of MDA-MB-231 cell proliferation compared to ETO or QC-SLNs alone. The combined treatment also notably increased the apoptosis pathway. QC-SLNs + ETO increased the Bax/Bcl-2 gene ratio, elevated p53 and p21 proteins, and activated caspase 3 and 9 enzymes. These results indicate the potential for QC-SLNs + ETO as a strategy for breast cancer treatment, potentially overcoming ETO-resistant breast cancer chemoresistance. Conclusion: These results suggest that QC-SLN has the potential to have a substantial impact on the breast cancer cure by improving the efficacy of ETO. This enhancement could potentially help overcome chemoresistance observed in ETO-resistant breast cancer.

Preclinical Safety Assessment of Lepidium sativum L. Seed Extract and its Nanoparticles via Acute and Subacute Oral Administration.

BACKGROUND: Lepidium sativum (LS) seed extract has various pharmacological properties, such as antioxidant, hepatoprotective, and anticancer activities. However, the translation of L. sativum seed extract to the clinical phase is still tedious due to its bioavailability and stability issues. This problem can be solved by encapsulating it in a nanodelivery system to improve its therapeutic potency. METHODS: In this study, we have determined and compared the in vivo toxicity of ethanolic extracts of L. sativum seeds (EELS) and solid lipid nanoparticles (SLNs). To conduct toxicity (acute and subacute toxicity) assessments, EELS and SLNs were orally administered to Swiss albino mice. Animal survival, body weight, the weight of vital organs in relation to body weight, haematological profile, biochemistry profile, and histopathological alterations were examined. RESULTS: Animals administered with 2000 mg/kg and 5000 mg/kg in an acute toxicity study exhibited no toxicological symptoms regarding behaviour, gross pathology, and body weight. As per a study on acute toxicity, the LD50 (lethal dose) for SLNs and EELS was over 400 mg/kg and over 5000 mg/kg, respectively. When animals were given SLNs (50 and 100 mg/kg, orally) and EELS (250, 500, and 1000 mg/kg, orally) for 28 days, subacute toxicity study did not exhibit any clinical changes. There were no differences in weight gain, haematological parameters, or biochemical parameters compared to the control groups (p > 0.05). The organs of the treated animals showed no abnormalities in the histological analysis (liver, heart, kidney, and spleen). CONCLUSION: The result confirms ethanolic extracts of L. sativum seeds and their SLNs to not have harmful effects following acute and subacute administration to mice. For further studies, patents available on Lepidium may be referred for its preclinical and clinical applications.

Weaponizing chitosan and its derivatives in the battle against lung cancer.

Lung cancer (LC) is a crisis of catastrophic proportions. It is a global problem and urgently requires a solution. The classic chemo drugs are lagging behind as they lack selectivity, where their side effects are spilled all over the body, and these adverse effects would be terribly tragic for LC patients. Therefore, they could make a bad situation worse, inflict damage on normal cells, and inflict pain on patients. Since our confidence in classic drugs is eroding, chitosan can offer a major leap forward in LC therapy. It can provide the backbone and the vehicle that enable chemo drugs to penetrate the hard shell of LC. It could be functionalized in a variety of ways to deliver a deadly payload of toxins to kill the bad guys. It is implemented in formulation of polymeric NPs, lipidic NPs, nanocomposites, multiwalled carbon nanotubes, and phototherapeutic agents. This review is a pretty clear proof of chitosan's utility as a weapon in battling LC. Chitosan-based formulations could work effectively to kill LC cells. If a researcher is looking for a vehicle for medication for LC therapy, chitosan can be an appropriate choice.

The mechanistic insights of essential oil of Mentha piperita to control Botrytis cinerea and the prospection of lipid nanoparticles to its application.

Botrytis cinerea is the phytopathogenic fungus responsible for the gray mold disease that affects crops worldwide. Essential oils (EOs) have emerged as a sustainable tool to reduce the adverse impact of synthetic fungicides. Nevertheless, the scarce information about the physiological mechanism action and the limitations to applying EOs has restricted its use. This study focused on elucidating the physiological action mechanisms and prospection of lipid nanoparticles to apply EO of Mentha piperita. The results showed that the EO of M. piperita at 500, 700, and 900 µL L-1 inhibited the mycelial growth at 100 %. The inhibition of spore germination of B. cinerea reached 31.43 % at 900 µL L-1. The EO of M. piperita decreased the dry weight and increased pH, electrical conductivity, and cellular material absorbing OD260 nm of cultures of B. cinerea. The fluorescence technique revealed that EO reduced hyphae width, mitochondrial activity, and viability, and increased ROS production. The formulation of EO of M. piperita loaded- solid lipid nanoparticles (SLN) at 500, 700, and 900 µL L-1 had particle size ∼ 200 nm, polydispersity index < 0.2, and stability. Also, the thermogravimetric analysis indicated that the EO of M. piperita-loaded SLN has great thermal stability at 50 °C. EO of M. piperita-loaded SLN reduced the mycelial growth of B. cinerea by 70 %, while SLN formulation (without EO) reached 42 % inhibition. These results supported that EO of M. piperita-loaded SLN is a sustainable tool for reducing the disease produced by B. cinerea.

Solid Lipid Nanoparticles Based on Babassu Oil and Copaiba Oleoresin: A Promising Approach for Prostate Cancer Therapy.

Solid lipid nanoparticles (SLNs) represent promising nanostructures for drug delivery systems. This study successfully synthesized SLNs containing different proportions of babassu oil (BBS) and copaiba oleoresin (COPA) via the emulsification-ultrasonication method. Before SLN synthesis, the identification and quantification of methyl esters, such as lauric acid and ß-caryophyllene, were performed via GC-MS analysis. These methyl esters were used as chemical markers and assisted in encapsulation efficiency experiments. A 22 factorial design with a center point was employed to assess the impact of stearic acid and Tween 80 on particle hydrodynamic diameter (HD) and polydispersity index (PDI). Additionally, the effects of temperature (8 ± 0.5 °C and 25 ± 1.0 °C) and time (0, 7, 15, 30, 40, and 60 days) on HD and PDI values were investigated. Zeta potential (ZP) measurements were utilized to evaluate nanoparticle stability, while transmission electron microscopy provided insights into the morphology and nanometric dimensions of the SLNs. The in vitro cytotoxic activity of the SLNs (10 µg/mL, 30 µg/mL, 40 µg/mL, and 80 µg/mL) was evaluated using the MTT assay with PC-3 and DU-145 prostate cancer cell lines. Results demonstrated that SLNs containing BBS and COPA in a 1:1 ratio exhibited a promising cytotoxic effect against prostate cancer cells, with a percentage of viable cells of 68.5% for PC-3 at a concentration of 30 µg/mL and 48% for DU-145 at a concentration of 80 µg/mL. These findings underscore the potential therapeutic applications of SLNs loaded with BBS and COPA for prostate cancer treatment.

Enzyme-Linked Lipid Nanocarriers for Coping Pseudomonal Pulmonary Infection. Would Nanocarriers Complement Biofilm Disruption or Pave Its Road?

Introduction: Cystic fibrosis (CF) is associated with pulmonary Pseudomonas aeruginosa infections persistent to antibiotics. Methods: To eradicate pseudomonal biofilms, solid lipid nanoparticles (SLNs) loaded with quorum-sensing-inhibitor (QSI, disrupting bacterial crosstalk), coated with chitosan (CS, improving internalization) and immobilized with alginate lyase (AL, destroying alginate biofilms) were developed. Results: SLNs (140-205 nm) showed prolonged release of QSI with no sign of acute toxicity to A549 and Calu-3 cells. The CS coating improved uptake, whereas immobilized-AL ensured >1.5-fold higher uptake and doubled SLN diffusion across the artificial biofilm sputum model. Respirable microparticles comprising SLNs in carbohydrate matrix elicited aerodynamic diameters MMAD (3.54, 2.48 µm) and fine-particle-fraction FPF (65, 48%) for anionic and cationic SLNs, respectively. The antimicrobial and/or antibiofilm activity of SLNs was explored in Pseudomonas aeruginosa reference mucoid/nonmucoid strains as well as clinical isolates. The full growth inhibition of planktonic bacteria was dependent on SLN type, concentration, growth medium, and strain. OD measurements and live/dead staining proved that anionic SLNs efficiently ceased biofilm formation and eradicated established biofilms, whereas cationic SLNs unexpectedly promoted biofilm progression. AL immobilization increased biofilm vulnerability; instead, CS coating increased biofilm formation confirmed by 3D-time lapse confocal imaging. Incubation of SLNs with mature biofilms of P. aeruginosa isolates increased biofilm density by an average of 1.5-fold. CLSM further confirmed the binding and uptake of the labeled SLNs in P. aeruginosa biofilms. Considerable uptake of CS-coated SLNs in non-mucoid strains could be observed presumably due to interaction of chitosan with LPS glycolipids in the outer cell membrane of P. aeruginosa. Conclusion: The biofilm-destructive potential of QSI/SLNs/AL inhalation is promising for site-specific biofilm-targeted interventional CF therapy. Nevertheless, the intrinsic/extrinsic fundamentals of nanocarrier-biofilm interactions require further investigation.

Co-delivery of paclitaxel and curcumin loaded solid lipid nanoparticles for improved targeting of lung cancer: In vitro and in vivo investigation.

The objective of this study was to develop nanotechnology-mediated paclitaxel (PAC) and curcumin (CUR) co-loaded solid lipid nanoparticles (PAC-CUR-SLNs) for the treatment of lung cancer, which is a leading cause of death worldwide. Around 85 % cases of lungs cancer constitute non-small cell lung cancer (NSCLC). PAC-CUR-SLNs were prepared via high pressure homogenization. The in vitro drug release of PAC-CUR-SLNs was checked followed by their in vitro cytotoxic investigation using adenocarcinomic human alveolar basal epithelial cells (A549) cell lines. Anticancer effects along with side effects of the synergistic delivery of PAC-CUR-SLNs were studied in vivo, using BALB/c mice. PAC-CUR-SLNs were nano sized (190 nm), homogeneously disseminated particles with %IE of both PAC and CUR above 94 %. PAC-CUR-SLNs released PAC and CUR in a controlled fashion when compared with free drug suspensions. The cytotoxicity of PAC-CUR-SLNs was higher than individual drug-loaded SLNs and pure drugs. Moreover, the co-delivery displayed synergistic effect, indicating potential of PAC-CUR-SLNs in lung cancer treatment. In vivo tumor investigation of PAC-CUR-SLNs exhibited 12-fold reduced tumor volume and almost no change in body weight of BALB/c mice, when compared with the experimental groups including control group. The inhibition of tumor rate on day 28 was 82.7 % in the PAC-CUR-SLNs group, which was significantly higher than the pure drugs and monotherapies. It can be concluded that, encapsulating the co-loaded antitumor drugs like PAC-CUR in SLNs may help in improved targeting of the tumor with enhanced anticancer effect.

Anti-Toxoplasma gondii activity of rose hip oil-solid lipid nanoparticles.

Toxoplasma gondii is a highly prevalent pathogen, reported from almost all geographical regions of the world. Current anti-T. gondii drugs are not effective enough in immunocompromised patients, encephalitis, chorioretinitis, and congenital toxoplasmosis. Therefore, the prescription of these drugs has been limited. Rose hip oil (RhO) is a natural plant compound, which shows antibacterial, anticancer, and anti-inflammatory activities. In the current study, the anti-T. gondii and cell toxicity effects of solid lipid nanoparticles (SLNs) loaded by RhO (RhO-SLNs) were evaluated. Emulsification sonicated-homogenization method was used to prepare SLNs. RhO-SLNs were characterized, and their anti-T. gondii and cell toxicity effects were evaluated using in vitro analyses. The particle size and the zeta potential of the nanoparticles were 152.09 nm and -15.3 mV nm, respectively. The entrapment efficiency percentage was 79.1%. In the present study, the inhibitory concentration (IC)50 against T. gondii was >1 µg/mL (p-value <.0001). The cell toxicity assay showed cytotoxicity concentration (CC)50 >10 mg/mL (p-value = .017). In addition, at least 75% of T. gondii-infected Vero cells remained alive at concentrations >10 mg/mL. The concentration of 1 mg/mL showed highest anti-Toxoplasma activity and lowest cell toxicity against the Vero cell. Our findings suggest that carrying natural plant compounds with SLNs could be considered an effective option for treatment strategies against T. gondii infections.

Evaluation of Silybin Nanoparticles against Liver Damage in Murine Schistosomiasis mansoni Infection.

Silybin (SIB) is a hepatoprotective drug known for its poor oral bioavailability, attributed to its classification as a class IV drug with significant metabolism during the first-pass effect. This study explored the potential of solid lipid nanoparticles with (SLN-SIB-U) or without (SLN-SIB) ursodeoxycholic acid and polymeric nanoparticles (PN-SIB) as delivery systems for SIB. The efficacy of these nanosystems was assessed through in vitro studies using the GRX and Caco-2 cell lines for permeability and proliferation assays, respectively, as well as in vivo experiments employing a murine model of Schistosomiasis mansoni infection in BALB/c mice. The mean diameter and encapsulation efficiency of the nanosystems were as follows: SLN-SIB (252.8 ± 4.4 nm, 90.28 ± 2.2%), SLN-SIB-U (252.9 ± 14.4 nm, 77.05 ± 2.8%), and PN-SIB (241.8 ± 4.1 nm, 98.0 ± 0.2%). In the proliferation assay with the GRX cell line, SLN-SIB and SLN-SIB-U exhibited inhibitory effects of 43.09 ± 5.74% and 38.78 ± 3.78%, respectively, compared to PN-SIB, which showed no inhibitory effect. Moreover, SLN-SIB-U demonstrated a greater apparent permeability coefficient (25.82 ± 2.2) than PN-SIB (20.76 ± 0.1), which was twice as high as that of SLN-SIB (11.32 ± 4.6) and pure SIB (11.28 ± 0.2). These findings suggest that solid lipid nanosystems hold promise for further in vivo investigations. In the murine model of acute-phase Schistosomiasis mansoni infection, both SLN-SIB and SLN-SIB-U displayed hepatoprotective effects, as evidenced by lower alanine amino transferase values (22.89 ± 1.6 and 23.93 ± 2.4 U/L, respectively) than those in control groups I (29.55 ± 0.7 U/L) and I+SIB (34.29 ± 0.3 U/L). Among the prepared nanosystems, SLN-SIB-U emerges as a promising candidate for enhancing the pharmacokinetic properties of SIB.

Enhanced efficacy of ß-carotene loaded solid lipid nanoparticles optimized and developed via central composite design on breast cancer cell lines.

ß-carotene is obtained from both plants and animals and has been the subject of intense research because of its provitamin-A, antioxidant, and anticancer effects. Its limited absorption and oxidative degradation significantly reduce its antitumor efficacy when taken orally. In our study, we utilize a central composite design to develop "bio-safe and highly bio-compatible" solid lipid nanoparticles (SLNs) by using only the combination of palmitic acid and poloxamer-407, a block co-polymer as a surfactant. The current research aim to develop and characterize SLNs loaded with ß-carotene to improve their bioavailability and therapeutic efficacy. In addition, the improved cytotoxicity of solid lipid nanoparticles loaded with ß-carotene was screened in-vitro in human breast cancer cell lines (MCF-7). The nanoparticles exhibits good stability, as indicated by their mean zeta potential of -26.3 ± 1.3 mV. The particles demonstrated high drug loading and entrapment capabilities. The fabricated nanoparticle's prolonged release potential was shown by the in-vitro release kinetics, which showed a first-order release pattern that adhered to the Higuchi model and showed a slow, linear, and steady release over 48 h. Moreover, a diffusion-type release mechanism was used to liberate ß-carotene from the nanoparticles. For six months, the nanoparticles also showed a notable degree of physical stability. Lastly, using the MTT assay, the anti-cancer properties of ß-carotene-loaded solid lipid nanoparticles were compared with intact ß-carotene on MCF-7 cell lines. The cytotoxicity tests have shown that the encapsulation of ß-carotene in the lipid bilayers of the optimized formulation does not interfere with the anti-cancer activity of the drug. When compared to standard ß-carotene, ß-carotene loaded SLNs showed enhanced anticancer efficacy and it is a plausible therapeutic candidate for enhancing the solubility of water-insoluble and degradation-sensitive biotherapeutics like ß-carotene.