This research demonstrates the design and development of a novel dual-targeting, pH-sensitive liposomal (pSL) formulation of 5-Fluorouracil (5-FU), i.e., (5-FU-iRGD-FA-pSL) to manage breast cancer (BC). The motivation to explore this formulation is to overcome the challenges of systemic toxicity and non-specific targeting of 5-FU, a conventional chemotherapeutic agent. The proposed formulation also combines folic acid (FA) and iRGD peptides as targeting ligands to enhance tumor cell specificity and penetration, while the pH-sensitive liposomes ensure the controlled drug release in the acidic tumor microenvironment. The physicochemical characterization revealed that 5-FU-iRGD-FA-pSL possesses optimal size, low polydispersity index, and favorable zeta potential, enhancing its stability and targeting capabilities. In vitro studies demonstrated significantly enhanced cellular uptake, cytotoxicity, and inhibition of cell migration in MCF-7 BC cells compared to free 5-FU and non-targeted liposomal formulations. DAPI staining revealed significant apoptotic features, including chromatin condensation (CC) and nuclear fragmentation (NF), with 5-FU-iRGD-FA-pSL inducing more pronounced apoptosis compared to 5-FU-pSL. Furthermore, in vivo analysis in a BC rat model showed superior anti-tumor efficacy, reduced systemic toxicity, and improved safety profile of the 5-FU-iRGD-FA-pSL formulation. This dual-targeting pSL system presents a promising approach for enhancing the therapeutic index of 5-FU, offering a potential strategy for more effective BC treatment.

Personalized treatment strategies have greatly improved the efficacy of anticancer drugs. Nanocarriers, especially liposomes, function as excellent platform for the delivery of both hydrophilic and hydrophobic agents. iRGD is a peptide composed of 9-amino acid denoted as (iRGDP), enhances selective and intratumoral delivery of anticancer drugs. Trastuzumab (TMAB), mainly targets HER2-positive advanced stage breast cancer is an FDA-approved monoclonal antibody. Gefitinib (GEB) is an anticancer drug, effective against metastatic breast cancer (MBC), while Lycorine hydrochloride (LCOH), a naturally derived compound, possess both anti-inflammatory and anticancer properties. This research is mainly emphasizing on the preparation of GEB and LCOH-entrapped TPGS-COOH coated-liposomes, camouflaged with an antibody (TMAB) and cyclic peptide (iRGDP) for targeted delivery in MBC therapy. The developed multifunctional liposomes were studied for extensive in vitro cell line studies on MCF-7 cells. The half-maximum inhibitory concentration (IC-50) values of GEB and LCOH co-loaded single functionalized liposome (SFL) (iRGDP-LiP, and TMAB-LiP) and dual-functionalized liposome (DFL) (iRGDP-TMAB-LiP) on MCF-7 cells were 1.04 ± 0.023 μg/mL, 0.71 ± 0.018 μg/mL, and 0.56 ± 0.028 μg/mL, respectively. Inverted confocal laser scanning microscopy (ICLSM) revealed enhanced cellular internalization in SFL and DFL-treated groups tagged with coumarin-6 and rhodamine-B dye as compared to conventional liposome. The scratch assay revealed a marked reduction in cell migration, while DAPI staining confirmed enhanced nuclear condensation (NC) and nuclear fragmentation (NF) in SFL and DFL-treated groups. Moreover, flow cytometry demonstrated enhanced early and late apoptosis in SFL and DFL groups. These findings indicate that GEB and LCOH co-loaded multifunctional liposome holds promise as a multifaceted therapeutic approach for MBC therapy. 

Multidrug resistance (MDR) infectious wounds are a major concern due to drug resistance, leading to increased patient morbidity. Lichenysin (LCN), a lipopeptide and biosurfactant obtained from certain strains of Bacillus licheniformis, has demonstrated an excellent antimicrobial property. The present study focuses on the fabrication and comprehensive evaluation of LCN-incorporated poly(vinyl alcohol) (PVA)/polycaprolactone (PCL)-based nanofiber scaffolds using an electrospinning technique as a potential wound healing biomaterial for the treatment of MDR infectious wounds in diabetic rats. The LCN-loaded PVA–PCL nanofiber scaffolds were characterized for their physicochemical, antimicrobial, in vitro cell line on L-929, hemocompatibility, flow cytometry, in vivo infectious wound healing, and enzyme-linked immuno sorbent assay (ELISA). Morphological analysis via scanning electron microscopy (SEM) images confirmed smooth and porous nanofibers with diameters in the range 200–300 nm. Fourier transform infrared and X-ray diffraction (XRD) results demonstrated the structural integrity, chemical compatibility, and amorphous nature of developed scaffolds. The scaffolds loaded with LCN demonstrated excellent water retention, moderate biodegradability, and sustained release of LCN for up to 72 h. Mechanical characterization demonstrated a robust tensile strength conducive to wound healing applications. Antimicrobial activity against Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) showed substantial antibacterial and antibiofilm activity. In vitro cell line studies showed enhanced cell adhesion, proliferation, migration, and viability, signifying the cytocompatibility of these scaffolds. In vivo studies demonstrated exceptional infectious wound healing potential in diabetic rats. These findings indicate that LCN-enriched PVA–PCL scaffolds hold significant potential as a therapeutic strategy for the treatment of MDR infectious wounds in diabetic rats through a multifaceted approach. 

Electrospinning is emerging as a versatile technique nanofibers fabrication because due to their unique properties such as large surface area to volume ratio, porosity and maintaining moist wound environment, the nanofibers are able to deliver sustained drug release and oxygen to the wound for rapid healing of diabetic wound. The present work was aimed to prepare and evaluate silk fibroin-curcumin based nanofiber in combination with polycaprolactone (PCL) and polyvinyl alcohol (PVA) which helped to strengthen the wound healing properties of nanofiber. Silk fibroin is a naturally occurring polymer was selected one polymer for making nanofibrous mat due to its unique properties such as biodegradability, permeability, oxygen supply and maintain moisture content in the wound. SEM results showed diameters of fibers varied in the range between 200 and 350 nm and their tensile strength ranged from 12.41 to 16.80 MP. The nanofibers were causing sustained release of curcumin for many hours. The in-vivo wound healing studies in streptozotocin-induced diabetic mice showed rapid wound healing efficacy as compared to conventional formulations. Furthermore, the histopathological studies evidenced its ability to restore the normal skin structure and histological conditions of tissues. The silk fibroin-based nanofiber wound dressing, therefore appears to be an ideal preparation, in combination with curcumin, because it blends the anti-oxidant, anti-inflammatory properties of curcumin. Therefore, it was concluded that the silk fibroin-based nanofiber loaded with curcumin has great healing potential in diabetic wound. 

Diabetes mellitus is a chronic disease with a high mortality rate and many complications. A non-healing diabetic foot ulcer (DFU) is one the most serious complications, leading to lower-extremity amputation in 15% of diabetic patients. Nanofibers are emerging as versatile wound dressing due to their unique wound healing properties, such as a high surface area to volume ratio, porosity, and ability to maintain a moist wound environment capable of delivering sustained drug release and oxygen supply to a wound. The present study was aimed to prepare and evaluate a polyvinyl alcohol (PVA)–sodium alginate (SA)–silk fibroin (SF)-based multifunctional nanofibrous scaffold loaded with asiaticoside (AT) in diabetic rats. The SEM findings showed that fibers’ diameters ranged from 100–200 nm, and tensile strengths ranged from 12.41–16.80 MPa. The crosslinked nanofibers were sustained AT over an extended period. The MTT and scratch assay on HaCat cells confirmed low cytotoxicity and significant cell migration, respectively. Antimicrobial tests revealed an excellent anti-microbial efficacy against P. aeruginosa and S. aureus bacteria. In-vivo study demonstrated better wound healing efficacy in diabetic rats. In addition, the histopathological studies showed its ability to restore the normal structure of the skin. The present study concluded that developed multifunctional nanofibers have a great potential for diabetic wound healing applications. 

Electrospun nanofibers scaffolds show promising potential in wound healing applications. This work aims to fabricate nanofibrous wound dressing as a novel approach for a topical drug delivery system. Herein, the electrospinning technique is used to design and fabricate bioabsorbable nanofibrous scaffolds of Polyvinyl alcohol/ gelatin/poly (lactic-co-glycolic acid) enriched with thrombin (TMB) as hemostatic agent and vancomycin (VCM) as anti-bacterial agent for a multifunctional platform to control excessive blood loss, inhibit bacterial growth and enhance wound healing. SEM, FTIR, XRD, in vitro drug release, antimicrobial studies, biofilm, cell viability assay, and in vivo study in a rat model were used to assess nanofiber’s structural, mechanical, and biological aspects. SEM images confirms the diameter of nanofibers which falls within the range from 150 to 300 nm for all the batches. Excellent swelling index data makes it suitable to absorb wound exudates. In-vitro drug release data shows sustained release behavior of nanofiber. Nanofibers scaffolds showed biomimetic behavior and excellent biocompatibility. Moreover, scaffolds exhibited excellent antimicrobial and biofilm activity against Staphylococcus aureus. Nanofibrous scaffolds showed less bleeding time, rapid blood coagulation, and excellent wound closure in a rat model. ELISA study demonstrated the decreasing level of inflammatory markers, such as TNF, IL1β, and IL-6, making formulation promising for hemostatic wound healing applications. Finally, the study concludes that nanofibrous scaffolds loaded with TMB and VCM have promising potential as a dressing material for hemostatic wound healing applications. 

Introduction: Foot ulceration is one of the most severe and debilitating complications of diabetes, which leads to the cause of non-traumatic lower-extremity amputation in 15– 24% of affected individuals. The healing of diabetic foot (DF) is a significant therapeutic problem due to complications from the multifactorial healing process. Electrospun nanofibrous scaffold loaded with various wound dressing materials has excellent wound healing properties due to its multifunctional action.

Purpose: This work aimed to develop and characterize chitosan (CS)-polyvinyl alcohol (PVA) blended electrospun multifunctional nanofiber loaded with curcumin (CUR) and zinc oxide (ZnO) to accelerate diabetic wound healing in STZ-induced diabetic rats.

Results: In-vitro characterization results revealed that nanofiber was fabricated successfully using the electrospinning technique. SEM results confirmed the smooth surface with web-like fiber nanostructure diameter ranging from 200 – 250 nm. An in-vitro release study confirmed the sustained release of CUR and ZnO for a prolonged time. In-vitro cell-line studies demonstrated significantly low cytotoxicity of nanofiber in HaCaT cells. Anti-bacterial studies demonstrated good anti-bacterial and anti-biofilm activities of nanofiber. In-vivo animal studies demonstrated an excellent wound-healing efficiency of the nanofibers in STZ–induced diabetic rats. Furthermore, the ELISA assay revealed that the optimized nanofiber membrane terminated the inflammatory phases successfully by downregulating the pro-inflammatory cytokines (TNF-α, MMP-2, and MMP-9) in wound healing. In-vitro and in-vivo studies conclude that the developed nanofiber loaded with bioactive material can promote diabetic wound healing efficiently via multifunction action such as the sustained release of bioactive molecules for a prolonged time of duration, proving anti-bacterial/anti-biofilm properties and acceleration of cell migration and proliferation process during the wound healing.

Discussion: CUR-ZnO electrospun nanofibers could be a promising drug delivery platform with the potential to be scaled up to treat diabetic foot ulcers effectively. 

Background: The healing of burn wounds is a complicated physiological process that involves several stages, including haemostasis, inflammation, proliferation, and remodeling to rebuild the skin and subcutaneous tissue integrity. Recent advancements in nanomaterials, especially nanofibers, have opened a new way for efficient healing of wounds due to burning or other injuries.

Methods: This study aims to develop and characterize collagen-decorated, bilayered electrospun nanofibrous mats composed of PVP and PVA loaded with Resveratrol (RSV) and Ampicillin (AMP) to accelerate burn wound healing and tissue repair.

Results: Nanofibers with smooth surfaces and web-like structures with diameters ranging from 200 to 400 nm were successfully produced by electrospinning. These fibres exhibited excellent in vitro properties, including the ability to absorb wound exudates and undergo biodegradation over a two-week period. Additionally, these nanofibers demonstrated sustained and controlled release of encapsulated Resveratrol (RSV) and Ampicillin (AMP) through in vitro release studies. The zone of inhibition (ZOI) of PVP-PVA-RSV-AMP nanofibers against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) was found 31±0.09 mm and 12±0.03, respectively, which was significantly higher as compared to positive control. Similarly, the biofilm study confirmed the significant reduction in the formation of biofilms in nanofiber-treated group against both S. aureus and E. coli. X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analysis proved the encapsulation of RSV and AMP successfully into nanofibers and their compatibility. Haemolysis assay (%) showed no significant haemolysis (less than 5%) in nanofiber-treated groups, confirmed their cytocompatibility with red blood cells (RBCs). Cell viability assay and cell adhesion on HaCaT cells showed increased cell proliferation, indicating its biocompatibility as well as non-toxic properties. Results of the in-vivo experiments on a burn wound model demonstrated potential burn wound healing in rats confirmed by H&E-stained images and also improved the collagen synthesis in nanofibers-treated groups evidenced by Masson-trichrome staining. The ELISA assay clearly indicated the efficient downregulation of TNF-alpha and IL-6 inflammatory biomarkers after treatment with nanofibers on day 10.

Conclusion: The RSV and AMP-loaded nanofiber mats, developed in this study, expedite burn wound healing through their multifaceted approach.

Current anticancer drug research includes tumor-targeted administration as a critical component because it is the best strategy to boost efficacy and decrease toxicity. Low drug concentration in cancer cells, nonspecific distribution, rapid clearance, multiple drug resistance, severe side effects, and other factors contribute to the disappointing results of traditional chemotherapy. As an innovative technique of treatments for hepatocellular carcinoma (HCC) in recent years, nanocarrier-mediated targeted drug delivery systems can overcome the aforesaid limitations via enhanced permeability and retention effect (EPR) and active targeting. Epidermal growth factor receptor (EGFR) inhibitor Gefitinib (Gefi) has dramatic effects on hepatocellular carcinoma. Herein, we developed and assessed an αvβ3 integrin receptor targeted c(RGDfK) surface modified liposomes for better targeting selectivity and therapeutic efficacy of Gefi on HCC cells. The conventional and modified Gefi loaded liposomes, i.e., denoted as Gefi-L and Gefi-c(RGDfK)-L, respectively, were prepared through the ethanol injection method and optimized via Box Behnken design (BBD). The FTIR and 1H NMR spectroscopy verified that the c(RGDfK) pentapeptides had formed an amide bond with the liposome surface. In addition, the particle size, Polydispersity index, zeta potential, encapsulation efficiency, and in-vitro Gefi release of the Gefi-L and Gefi-c(RGDfK)-L were measured and analyzed. As indicated by the MTT assay on HepG2 cells, Gefi-c(RGDfK)-L displayed considerably higher cytotoxicity than Gefi-L or Gefi alone. Throughout the incubation period, HepG2 cells took up significantly more Gefi-c(RGDfK)-L than Gefi-L. According to the in vivo biodistribution analysis, Gefi-c(RGDfK)-L accumulated more strongly at the tumor site than Gefi-L and free Gefi. Furthermore, HCC-bearing rats treated with Gefi-c(RGDfK)-L showed a substantial drop in liver marker enzymes (alanine transaminase, alkaline phosphatase, aspartate transaminase, and total bilirubin levels) compared to the disease control group. Gefi-c(RGDfK)-L suppresses tumour growth more effectively than Gefi-L and free Gefi, according to an in vivo analysis of their anticancer activities. Thus, c(RGDfK)-surface modified liposomes, i.e., Gefi-c(RGDfK)-L may serve as an efficient carrier for the targeted delivery of anticancer drugs. 

The morbidity rate following a surgical procedure increasing rapidly in the cases associated with surgical site infections. Traditional sutures lack the ability to deliver drugs as the incorporation of the drug in their structure would hamper their mechanical properties. To prevent such infections, we developed an extracellular matrix mimicking electrospun nanofibrous yarns of poly-(D,L)-lactic acid and polyvinyl alcohol loaded with vancomycin and ferulic acid, prepared by uniaxial electrospinning technique. In-vitro characterization such as scanning electron microscopy, Fourier transform infrared spectroscopy, x-ray diffraction, tensile strength testing, degradation studies, and antimicrobial studies along with in-vivo evaluation done with help of incision wound healing rat model and simultaneous testing of microbial load in the incised tissue. The in-vitro studies indicated the nanofiber yarns have size range 200–300 nm with a tensile strength of 7.54 ± 0.58 MPa. The dual drug-loaded yarn showed sustained drug release over a period of 48 h. In-vitro water uptake and biodegradation data indicated optimum results suitable for suturing applications. Antimicrobial study showed excellent antimicrobial activity against both S. aureus and E. coli. Results obtained from in-vivo study suggested excellent wound healing potential of nanofiber yarns as compared with commercial silk sutures. The histopathological studies confirmed restoring ability of nanofiber yarn to the normal skin structure. Enzyme-linked immunosorbent assay (ELISA) study revealed the downregulation of inflammatory markers i.e. TNF-alpha and IL-6, making nanofibers sutures suitable for surgical wound healing applications. Overall, the present study may conclude that the developed dual drug-loaded nanofiber yarns have excellent potential in surgical wound healing applications. 

The advent of pH-sensitive liposomes (pHLips) has opened new opportunities for the improved and targeted delivery of antitumor drugs as well as gene therapeutics. Comprising fusogenic dioleylphosphatidylethanolamine (DOPE) and cholesteryl hemisuccinate (CHEMS), these nanosystems harness the acidification in the tumor microenvironment and endosomes to deliver drugs effectively. pH-responsive liposomes that are internalized through endocytosis encounter mildly acidic pH in the endosomes and thereafter fuse or destabilize the endosomal membrane, leading to subsequent cargo release into the cytoplasm. The extracellular tumor matrix also presents a slightly acidic environment that can lead to the enhanced drug release and improved targeting capabilities of the nano-delivery system. Recent studies have shown that folic acid (FA) and iRGD-coated nanocarriers, including pH-sensitive liposomes, can preferentially accumulate and deliver drugs to breast tumors that overexpress folate receptors and αvβ3 and αvβ5 integrins. This study focuses on the development and characterization of 5-Fluorouracil (5-FU)-loaded FA and iRGD surface-modified pHLips (FA-iRGD-5-FU-pHLips). The novelty of this research lies in the dual targeting mechanism utilizing FA and iRGD peptides, combined with the pH-sensitive properties of the liposomes, to enhance selective targeting and uptake by cancer cells and effective drug release in the acidic tumor environment. The prepared liposomes were small, with an average diameter of 152 ± 3.27 nm, uniform, and unilamellar, demonstrating efficient 5-FU encapsulation (93.1 ± 2.58%). Despite surface functionalization, the liposomes maintained their pH sensitivity and a neutral zeta potential, which also conferred stability and reduced aggregation. Effective pH responsiveness was demonstrated by the observation of enhanced drug release at pH 5.5 compared to physiological pH 7.4. (84.47% versus 46.41% release at pH 5.5 versus pH 7.4, respectively, in 72 h). The formulations exhibited stability for six months and were stable when subjected to simulated biological settings. Blood compatibility and cytotoxicity studies on MDA-MB-231 and SK-BR3 breast cancer cell lines revealed an enhanced cytotoxicity of the liposomal formulation that was modified with FA and iRGD compared to free 5-FU and minimal hemolysis. Collectively, these findings support the potential of FA and iRGD surface-camouflaged, pH-sensitive liposomes as a promising drug delivery strategy for breast cancer treatment. 

Background: Antitumor research aims to efficiently target hepatocarcinoma cells (HCC) for drug delivery. Nanostructured lipid carriers (NLCs) are promising for active tumour targeting. Cell-penetrating peptides are feasible ligands for targeted cancer treatment.

Methods: In this study, we optimized gefitinib-loaded NLCs (GF-NLC) for HCC treatment. The NLCs contained cholesterol, oleic acid, Pluronic F-68, and Phospholipon 90G. The NLC surface was functionalized to enhance targeting with the cRGDfK-pentapeptide, which binds to the αvβ3 integrin receptor overexpressed on hepatocarcinoma cells.

Results: GF-NLC formulation was thoroughly characterized for various parameters using differential scanning calorimetry and X-ray diffraction analysis. In-vitro and in-vivo studies on the HepG2 cell line showed cRGDfK@GF-NLC’s superiority over GF-NLC and free gefitinib. cRGDfK@GF-NLC exhibited significantly higher cytotoxicity, growth inhibition, and cellular internalization. Biodistribution studies demonstrated enhanced tumour site accumulation without organ toxicity. The findings highlight cRGDfK@GF-NLC as a highly efficient carrier for targeted drug delivery, surpassing non-functionalized NLCs. These functionalized NLCs offer promising prospects for improving hepatocarcinoma therapy outcomes by specifically targeting HCC cells. 

Conclusion: Based on these findings, cRGDfK@GF-NLC holds immense potential as a highly efficient carrier for targeted drug delivery of anticancer agents, surpassing the capabilities of non-functionalized NLCs. This research opens up new avenues for effective treatment strategies in hepatocarcinoma.

Myocardial infarction (MI) is a severe manifestation of ischemic heart disease (IHD) that impacts cardiac functions. Naringin is a bioflavonoid also known as 4-trihydroxy-flavonone-7-rhamnoglucoside, that offers numerous pharmacological benefits including antidiabetic, cardioprotective, and neuroprotective activities. Despite its benefits, the poor water solubility of naringin limits its drug delivery application. The objective of the investigation is to develop, optimize and evaluate the nanoparticles loaded with naringin (NR-LGNPs) by using lignin and Tween 80 as polymers and stabilizers, respectively. The NR-LGNPs were prepared using a modified phase separation technique while the composition as well as process variables of the NR-LGNPs were optimized using 23 factorial design of the experiment. The optimized formulation was subsequently characterized for various in vitro and in vivo parameters. The formulated optimized polymeric nanoparticles were spherical and had a size of 138.24 ± 1.36 nm with entrapment efficiency of 91.53 ± 0.84 %. The in vitro drug release was found to be 88.75 ± 1.54 % at the end of 24 h. The administration of LG-NPs at a dosage of 10 mg/kg through intravenous injection demonstrated a significant ability to mitigate the levels of creatine kinase-myoglobin binding (CK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), lipid peroxidation (MDA) following in vivo animal model. The tissue histopathology study indicated the significant potential for restoration of cardiac tissue damage upon treatment with NR-LGNPs. Additionally, it was observed that the treatment with LG-NPs improved the size of the cardiac infarction, indicating its potent cardioprotective activity to combat myocardial damage induced by ISO. Thus, the enhancement of NR bioactivity through nanotechnology could potentially mitigate cardiac damage due to myocarial infarction 

Human epidermal growth factor receptor-2 (HER2)-positive breast cancer metastasis remains the primary cause of mortality among women globally. Targeted therapies have revolutionized treatment efficacy, with Trastuzumab (Trast), a monoclonal antibody, targeting HER2-positive advanced breast cancer. The tumor-homing peptide iRGD enhances the intratumoral accumulation and penetration of therapeutic agents. Liposomes serve as versatile nanocarriers for both hydrophilic and hydrophobic drugs. Gefitinib (GFB) is a potential anticancer drug against HER2-positive breast cancer, while Lycorine hydrochloride (LCH) is a natural compound with anticancer and anti-inflammatory properties. This study developed TPGS-COOH-coated liposomes co-loaded with GFB and LCH, prepared by the solvent injection method, and surface-functionalized with Trast and iRGD. The dual surface-decorated liposomes (DSDLs) were characterized for their particle size (PS), polydispersity index (PDI), zeta potential (ZP), surface chemistry, surface morphology, and their crystallinity during in-vitro drug release, drug encapsulation, and in-vitro cell line studies on SK-BR-3 and MDA-MB-231 breast cancer cells. The half-maximum inhibitory concentration (IC-50) values of single decorated liposomes (SDLs), iRGD-LP, and Trast-LP, as well as DSDLs (iRGD-Trast-LP) on SK-BR-3 cells, were 6.10 ± 0.42, 4.98 ± 0.36, and 4.34 ± 0.32 μg/mL, respectively. Moreover, the IC-50 values of SDLs and DSDLs on MDA-MB-231 cells were 15.12 ± 0.68, 13.09 ± 0.59, and 11.08 ± 0.48 μg/mL, respectively. Cellular uptake studies using confocal laser scanning microscopy (CLSM) showed that iRGD and Trast functionalization significantly enhanced cellular uptake in both cell lines. The wound-healing assay demonstrated a significant reduction in SDL and DSDL-treated MDA-MB-231 cell migration compared to the control. Additionally, the blood compatibility study showed minimal hemolysis (less than 5% RBC lysis), indicating good biocompatibility and biosafety. Overall, these findings suggest that TPGS-COOH-coated, GFB and LCH co-loaded, dual-ligand (iRGD and Trast) functionalized, multifunctional liposomes could be a promising therapeutic strategy for treating HER2-positive metastatic breast cancer.

Cardiotoxicity (CT) is a severe condition that negatively impacts heart function. β-sitosterol (BS) is a group of phytosterols and known for various pharmacological benefits, such as managing diabetes, cardiac protection, and neuroprotection. This study aims to develop niosomes (NS) containing BS, utilizing cholesterol as the lipid and Tween 80 as the stabilizer. The research focuses on designing and evaluating both conventional BS-NS and hyaluronic acid (HA) modified NS (BS-HA-NS) to enhance the specificity and efficacy of BS within cardiac tissue. The resulting niosomal formulation was spherical, with a size of about 158.51 ± 0.57 nm, an entrapment efficiency of 93.56 ± 1.48 %, and a drug loading of 8.07 ± 1.62 %. To evaluate cytotoxicity on H9c2 heart cells, the MTT assay was used. The cellular uptake of BS-NS and BS-HA-NS was confirmed by confocal microscopy on H9c2 cardiac cells. Administering BS-NS and BS-HA-NS intravenously at a dose of 10 mg/kg showed the ability to significantly decrease the levels of cardiac troponin-I (cTn-I), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and lipid peroxidation (MDA). Tissue histopathology indicated a substantial potential for repairing cardiac tissue after treatment with BS-NS and BS-HA-NS and strong cardioprotection against ISO induced myocardial tissue damages. Thus, enhancing BS's therapeutic effectiveness through niosome surface modification holds promise for mitigating cardiac damage resulting from CT.