Unleashing the biomimetic targeting potential of platelet-derived nanocarriers on atherosclerosis.

Atherosclerosis, the primary mechanism underlying the development of many cardiovascular illnesses, continues to be one of the leading causes of mortality worldwide. Platelet (PLT), which are essential for maintaining body homeostasis, have been strongly linked to the onset of atherosclerosis at various stages due to their inherent tendency to bind to atherosclerotic lesions and show an affinity for plaques. Therefore, mimicking PLT's innate adhesive features may be necessary to effectively target plaques. PLT-derived nanocarriers have emerged as a promising biomimetic targeting strategy for treating atherosclerosis due to their numerous advantages. These advantages include excellent biocompatibility, minimal macrophage phagocytosis, prolonged circulation time, targeting capability for impaired vascular sites, and suitability as carriers for anti-atherosclerotic drugs. Herein, we discuss the role of PLT in atherogenesis and propose the design of nanocarriers based on PLT-membrane coating and PLT-derived vesicles. These nanocarriers can target multiple biological elements relevant to plaque development. The review also emphasizes the current challenges and future research directions for the effective utilization of PLT-derived nanocarriers in treating atherosclerosis.

T Cell and Natural Killer Cell Membrane-Camouflaged Nanoparticles for Cancer and Viral Therapies.

Extensive research has been conducted on the application of nanoparticles in the treatment of cancer and infectious diseases. Due to their exceptional characteristics and flexible structure, they are classified as highly efficient drug delivery systems, ensuring both safety and targeted delivery. Nevertheless, nanoparticles still encounter obstacles, such as biological instability, absence of selectivity, recognition as unfamiliar elements, and quick elimination, which restrict their remedial capacity. To surmount these drawbacks, biomimetic nanotechnology has been developed that utilizes T cell and natural killer (NK) cell membrane-encased nanoparticles as sophisticated methods of administering drugs. These nanoparticles can extend the duration of drug circulation and avoid immune system clearance. During the membrane extraction and coating procedure, the surface proteins of immunological cells are transferred to the biomimetic nanoparticles. Such proteins present on the surface of cells confer several benefits to nanoparticles, including prolonged circulation, enhanced targeting, controlled release, specific cellular contact, and reduced in vivo toxicity. This review focuses on biomimetic nanosystems that are derived from the membranes of T cells and NK cells and their comprehensive extraction procedure, manufacture, and applications in cancer treatment and viral infections. Furthermore, potential applications, prospects, and existing challenges in their medical implementation are highlighted.

Old drug, new tricks: polymer-based nanoscale systems for effective cytarabine delivery.

Cytarabine, an antimetabolite antineoplastic agent, has been utilized to treat various cancers. However, because of its short half-life, low stability, and limited bioavailability, achieving an optimal plasma concentration requires continuous intravenous administration, which can lead to toxicity in normal cells and tissues. Addressing these limitations is crucial to optimize the therapeutic efficacy of cytarabine while minimizing its adverse effects. The use of novel drug delivery systems, such as polymer-based nanocarriers have emerged as promising vehicles for targeted drug delivery due to their unique properties, including high stability, biocompatibility, and tunable release kinetics. In this review, we examine the application of various polymer-based nanocarriers, including polymeric nanoparticles, polymeric micelles, dendrimers, polymer-drug conjugates, and nano-hydrogels, for the delivery of cytarabine. The article highlights the limitations of conventional cytarabine administration which often lead to suboptimal therapeutic outcomes and systemic toxicity. The rationale for using polymer-based nanocarriers is discussed, highlighting their ability to overcome challenges by providing controlled drug release, improved stability, and enhanced targeting capabilities. In summary, this review offers a valuable resource for drug delivery scientists by providing insights into the design principles, formulation strategies, and potential applications of polymer-based nanocarriers that can enhance the therapeutic efficacy of cytarabine.

Biomimetic cell membrane-coated poly(lactic-co-glycolic acid) nanoparticles for biomedical applications.

Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are commonly used for drug delivery because of their favored biocompatibility and suitability for sustained and controlled drug release. To prolong NP circulation time, enable target-specific drug delivery and overcome physiological barriers, NPs camouflaged in cell membranes have been developed and evaluated to improve drug delivery. Here, we discuss recent advances in cell membrane-coated PLGA NPs, their preparation methods, and their application to cancer therapy, management of inflammation, treatment of cardiovascular disease and control of infection. We address the current challenges and highlight future research directions needed for effective use of cell membrane-camouflaged NPs.

Solid lipid-based nanoparticulate system for sustained release and enhanced in-vitro cytotoxic effect of 5-fluorouracil on skin Melanoma and squamous cell carcinoma.

The present study aimed to prepare solid lipid-based nanoparticles (SLNs) using Precirol® ATO 5 as solid lipid and Poloxamer 188 and Tween 80 as surfactant and co-surfactant respectively, and SLNs-derived gel for sustained delivery, enhanced in-vitro cytotoxicity, enhanced cellular uptake of 5-FU and enhanced permeation of 5-FU across the skin. The 5-FU-loaded SLNs were prepared by the hot melt encapsulation method and converted into SLN-derived gel using a gelling agent (Carbopol 940). The 5-FU-loaded SLNs had a particle size in the range of 76.82±1.48 to 327±4.46 nm, zeta potential between -11.3±2.11 and -28.4±2.40 mV, and entrapment efficiency (%) in range of 63.46±1.13 and 76.08±2.42. The FTIR analysis depicted that there was no chemical interaction between 5-FU and formulation components. Differential scanning calorimetric analysis showed thermal stability of 5-FU in the nanoparticles and powdered X-ray diffraction analysis revealed successful incorporation of 5-FU in nanoparticles. The in-vitro release study of 5-FU-loaded SLNs showed biphasic release behavior with initial burst release followed by sustained release over 48 hr. The 5-FU-loaded SLNs showed a greater cytotoxic effect on skin melanoma (B16F10 cells) and squamous cell carcinoma (A-431 cells) as compared to free 5-FU drug solution after 48 hr. Flow cytometry and fluorescence microscopy displayed enhanced quantitative and qualitative cellular uptake of SLNs. The SLNs formulation showed acceptable safety and biocompatible profile after an acute toxicity study in Wistar rats. Moreover, ex-vivo permeation studies depicted 2.13±0.076 folds enhanced flux of 5-FU-loaded SLN derived gel compared to 5-FU plain gel, and skin retention studies revealed target efficiency (%) 2.54±0.03 of 5-FU-loaded SLN derived gel compared to 5-FU plain gel.

Comprehensive Biological Potential, Phytochemical Profiling Using GC-MS and LC-ESI-MS, and In-Silico Assessment of Strobilanthes glutinosus Nees: An Important Medicinal Plant.

Plants of the genus Strobilanthes have notable use in folklore medicines as well as being used for pharmacological purposes. The present work explored the biological predispositions of Strobilanthes glutinosus and attempted to accomplish a comprehensive chemical profile through GC-MS of different fractions concerning polarity (chloroform and n-butanol) and LC-ESI-MS of methanolic extract by both positive and negative ionization modes. The biological characteristics such as antioxidant potential were assessed by applying six different methods. The potential for clinically relevant enzyme (α-amylase, α-glucosidase, and tyrosinase) inhibition was examined. The DPPH, ABTS, CUPRAC, and FRAP results revealed that the methanol fraction presented efficient results. The phosphomolybdenum assay revealed that the n-hexane fraction showed the most efficient results, while maximum metal chelation potential was observed for the chloroform fraction. The GC-MS profiling of n-butanol and chloroform fractions revealed the existence of several (110) important compounds presenting different classes (fatty acids, phenols, alkanes, monoterpenes, diterpenes, sesquiterpenoids, and sterols), while LC-ESI-MS tentatively identified the presence of 44 clinically important secondary metabolites. The n-hexane fraction exhibited the highest potential against α-amylase (497.98 mm ACAE/g extract) and α-glucosidase (605.85 mm ACAE/g extract). Significant inhibitory activity against tyrosinase enzyme was displayed by fraction. Six of the prevailing compounds from the GC-MS study (lupeol, beta-amyrin, stigmasterol, gamma sitosterol, 9,12-octadecadienoic acid, and n-hexadecanoic acid) were modelled against α-glucosidase and α-amylase enzymes along with a comparison of binding affinity to standard acarbose, while three compounds identified through LC-ESI-MS were docked to the mushroom tyrosinase enzyme and presented with significant biding affinities. Thus, it is assumed that S. glutinosus demonstrated effective antioxidant and enzyme inhibition prospects with effective bioactive molecules, potentially opening the door to a new application in the field of medicine.

Folate decorated lipid chitosan hybrid nanoparticles of 5-fluorouracil for enhanced anticancer efficacy against colon cancer.

The study aimed to develop folate decorated lipid chitosan hybrid nanoparticles for targeted delivery of 5-fluorouracil in colon cancer by utilizing the overexpressed folate receptors on the surface of HT-29 and HCT 116 cancer cell lines. The developed formulations were prepared by the ionic gelation method with slight modifications. The developed formulations exhibited spherical morphology, smaller particle size (158 to 225 nm), zeta potential (32.24 to 35.95 mV), PDI (0.19 to 0.35), and high encapsulation efficiency (85.3 % to 94.2 %) with optimal physicochemical characteristics. The in vitro release showed a biphasic release pattern with an initial burst release followed by a sustained release for 48 h. Moreover, the in vitro cell line study revealed that FA-CLPN-2 exhibited an enhanced cellular uptake and greater cytotoxic effect in HT-29 and HCT 116 cell lines compared to non-targeted CLPN-2 and free drug solution due to the folate receptor facilitated endocytosis process. The in vivo toxicity study revealed the safety and biocompatibility of the developed formulations in biological systems. The stability study demonstrates the stability of the developed formulations. Overall, these results suggest that the folate decorated lipid chitosan hybrid nanoparticles could be used as a potential delivery system for tumor-targeted therapy with reduced side effects.

pH-Responsive Liposomes of Dioleoyl Phosphatidylethanolamine and Cholesteryl Hemisuccinate for the Enhanced Anticancer Efficacy of Cisplatin.

The current study aimed to develop pH-responsive cisplatin-loaded liposomes (CDDP@PLs) via the thin film hydration method. Formulations with varied ratios of dioleoyl phosphatidylethanolamine (DOPE) to cholesteryl hemisuccinate (CHEMS) were investigated to obtain the optimal particle size, zeta potential, entrapment efficiency, in vitro release profile, and stability. The particle size of the CDDP@PLs was in the range of 153.2 ± 3.08-206.4 ± 2.26 nm, zeta potential was -17.8 ± 1.26 to -24.6 ± 1.72, and PDI displayed an acceptable size distribution. Transmission electron microscopy revealed a spherical shape with ~200 nm size. Fourier transform infrared spectroscopic analysis showed the physicochemical stability of CDDP@PLs, and differential scanning calorimetry analysis showed the loss of the crystalline nature of cisplatin in liposomes. In vitro release study of CDDP@PLs at pH 7.4 depicted the lower release rate of cisplatin (less than 40%), and at a pH of 6.5, an almost 65% release rate was achieved compared to the release rate at pH 5.5 (more than 80%) showing the tumor-specific drug release. The cytotoxicity study showed the improved cytotoxicity of CDDP@PLs compared to cisplatin solution in MDA-MB-231 and SK-OV-3 cell lines, and fluorescence microscopy also showed enhanced cellular internalization. The acute toxicity study showed the safety and biocompatibility of the developed carrier system for the potential delivery of chemotherapeutic agents. These studies suggest that CDDP@PLs could be utilized as an efficient delivery system for the enhancement of therapeutic efficacy and to minimize the side effects of chemotherapy by releasing cisplatin at the tumor site.

Fabrication, in vitro and ex vivo evaluation of proliposomes and liposomal derived gel for enhanced solubility and permeability of diacerein.

The present study is associated with the development of proliposomes and liposomal derived gel for enhanced solubility and permeability of diacerein. Proliposomes were developed by thin film hydration method and converted into the liposomal derived gel using carbopol-934 as a gelling agent. Formulations with varied lecithin to cholesterol ratios were investigated to obtain the optimal size, entrapment efficiency, and enhanced in vitro dissolution. Dynamic light scattering analysis revealed the particle size and zeta potential in the range of 385.1±2.45-762.8±2.05 nm and -22.4±0.55-31.2±0.96mV respectively. Fourier transform infrared (FTIR) spectroscopic analysis depicted the physicochemical compatibility, powdered x-ray diffraction (PXRD) analysis predicted the crystalline nature of pure drug and its transition into amorphous form within formulation. The differential scanning calorimetry (DSC) demonstrated the thermal stability of the formulation. The in vitro drug release study using dialysis membrane displayed the enhanced dissolution of diacerein due to the presence of hydrophilic carrier (Maltodextrin) followed by sustained drug release due to the presence of lipid mixture (lecithin and cholesterol). Ex vivo permeation studies depicted 3.50±0.27 and 3.21±0.22 folds enhanced flux of liposomal gels as compared to control. The acute oral toxicity study showed safety and biocompatibility of the system as no histopathological changes in vital organs were observed. These results suggests that proliposomes and liposomal derived gel are promising candidates for the solubility and permeability enhancement of diacerein in the management of osteoarthritis.

Mild Hyperthermia Responsive Liposomes for Enhanced In Vitro and In Vivo Anticancer Efficacy of Doxorubicin against Hepatocellular Carcinoma.

The current study is aimed to fabricate doxorubicin (Dox) loaded mild temperature responsive liposomes (MTLs) by thin film hydration technique for enhanced in vitro and in vivo anticancer efficacy against hepatocellular carcinoma. The aforementioned Dox loaded MTLs were developed and optimized with extrusion and drug loading techniques. The optimized MTLs were in optimum size range (118.20 ± 2.81-187.13 ± 4.15 nm), colloidal stability (-13.27 ± 0.04 to -32.34 ± 0.15 mV), and enhanced entrapment of Dox (28.71 ± 2.01-79.24 ± 2.16). Furthermore, the optimized formulation (MTL1-E(AL)) embodied improved physicochemical stability deducted by Fourier transform infra-red (FTIR) spectroscopy and mild hyperthermia-based phase transition demonstrated from differential scanning calorimetry (DSC). An in vitro drug release study revealed mild hyperthermia assisted rapid in vitro Dox release from MTLs-E(AL) (T100% ≈ 1 h) by Korsmeyer-Peppas model based Fickian diffusion (n < 0.45). Likewise, an in vitro cytotoxicity study and lower IC50 values also symbolized mild hyperthermia (40.2 °C) based quick and improved cytotoxicity of MTL1-E(AL) in HepG2 and MCF-7 cells than Dox. The fluorescence microscopy also represented enhanced cellular internalization of MTL1-E(AL) at mild hyperthermia compared to the normothermia (37.2 °C). In addition, an in vivo animal study portrayed the safety, improved anticancer efficacy and healing of hepatocellular carcinoma (HCC) through MTL1-E(AL). In brief, the Dox loaded MTLs could be utilized as safe and effective therapeutic strategy against HCC.

Lipid poly (ɛ-caprolactone) hybrid nanoparticles of 5-fluorouracil for sustained release and enhanced anticancer efficacy.

AIMS: The present study aimed to develop and characterize poly (ɛ-caprolactone) (PCL) based lipid polymer hybrid nanoparticles for sustained delivery and in-vitro anti-cancer activity in MCF-7 and HeLa cells cancer cell line. MATERIALS AND METHODS: The nanoprecipitation method was used for the development of 5-fluorouracil loaded lipid polymer hybrid nanoparticles (LPHNPs). The developed LPHNPs were characterized for physicochemical characteristics and the anti-cancer effect was evaluated in MCF-7 and HeLa cells. SIGNIFICANT FINDINGS: Six formulations having fixed amount of drug and varied lipid, polymer and emulsifier concentrations were prepared. The particle size was in the range of 174 ± 4 to 267 ± 2.65 nm, entrapment efficiency (92.87 ± 0.594 to 94.13 ± 0.772%), negative zeta potential, optimum polydispersity index and spherical shape. FTIR analysis shows no chemical interaction among the formulation components, DSC analysis reveals the disappearance of 5-FU melting endotherm in the developed LPHNPs suggesting amorphization of 5-FU in the developed system, XRD analysis indicates successful encapsulation of the drug in the lipid polymer matrix. The in-vitro release shows a biphasic release pattern with an initial burst release followed by a sustained release profile for 72 h. The drug loaded LPHNPs exhibited a greater cytotoxic effect than 5-FU solution due to sustained release and increased cellular internalization. The acute toxicity study revealed the safety of the developed carrier system for potential delivery of chemotherapeutic agents. SIGNIFICANCE: The developed LPHNPs of 5-fluorouracil will provide the sustained release behavior of 5-fluorouracil to maximize the therapeutic efficacy and minimize the dose related toxicity.

Cell membrane cloaked nanomedicines for bio-imaging and immunotherapy of cancer: Improved pharmacokinetics, cell internalization and anticancer efficacy.

Despite enormous advancements in the field of oncology, the innocuous and effectual treatment of various types of malignancies remained a colossal challenge. The conventional modalities such as chemotherapy, radiotherapy, and surgery have been remained the most viable options for cancer treatment, but lacking of target-specificity, optimum safety and efficacy, and pharmacokinetic disparities are their impliable shortcomings. Though, in recent decades, numerous encroachments in the field of onco-targeted drug delivery have been adapted but several limitations (i.e., short plasma half-life, early clearance by reticuloendothelial system, immunogenicity, inadequate internalization and localization into the onco-tissues, chemoresistance, and deficient therapeutic efficacy) associated with these onco-targeted delivery systems limits their clinical viability. To abolish the aforementioned inadequacies, a promising approach has been emerged in which stealthing of synthetic nanocarriers has been attained by cloaking them into the natural cell membranes. These biomimetic nanomedicines not only retain characteristics features of the synthetic nanocarriers but also inherit the cell-membrane intrinsic functionalities. In this review, we have summarized preparation methods, mechanism of cloaking, and pharmaceutical and therapeutic superiority of cell-membrane camouflaged nanomedicines in improving the bio-imaging and immunotherapy against various types of malignancies. These pliable adaptations have revolutionized the current drug delivery strategies by optimizing the plasma circulation time, improving the permeation into the cancerous microenvironment, escaping the immune evasion and rapid clearance from the systemic circulation, minimizing the immunogenicity, and enabling the cell-cell communication via cell membrane markers of biomimetic nanomedicines. Moreover, the preeminence of cell-membrane cloaked nanomedicines in improving the bio-imaging and theranostic applications, alone or in combination with phototherapy or radiotherapy, have also been pondered.

Statistically optimized pentazocine loaded microsphere for the sustained delivery application: Formulation and characterization.

Pentazocine (PTZ) is a narcotic analgesic used to manage moderate to severe, acute and chronic pains. In this study, PTZ loaded Ethyl cellulose microsphere has been formulated for sustained release and improved bioavailability of PTZ. These microspheres were fabricated by oil in water emulsion solvent evaporation technique. A three factorial, three levels Box-Behnken design was applied to investigate the influence of different formulation components and process variables on the formulation response using the numeric approach through the design expert® software. All the formulations were characterized for the morphology, different physicochemical properties and the results were supported with the ANOVA analysis, three dimensional contour graphs and regression equations. The maximum percentage yield was 98.67% with 98% entrapment of PTZ. The mean particle size of the formulations ranges from 50-148µm, which directly relates to the concentration of polymer and inversely proportional to the stirring speed. SEM revealed the spherical shape of PTZ microspheres with porous structures. These are physically, chemically and thermally stable as confirmed through Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD) and thermal gravimetric (TG) analysis respectively. The microspheres provided a sustained release of the PTZ for more than 12 hours, following zero order with fickian and non fickian diffusion. The results indicate that prepared microspheres can be a potential drug delivery system (DDS) for the delivery of PTZ in the management of pains.

Recent Advancements in Stimuli Responsive Drug Delivery Platforms for Active and Passive Cancer Targeting.

The tumor-specific targeting of chemotherapeutic agents for specific necrosis of cancer cells without affecting the normal cells poses a great challenge for researchers and scientists. Though extensive research has been carried out to investigate chemotherapy-based targeted drug delivery, the identification of the most promising strategy capable of bypassing non-specific cytotoxicity is still a major concern. Recent advancements in the arena of onco-targeted therapies have enabled safe and effective tumor-specific localization through stimuli-responsive drug delivery systems. Owing to their promising characteristic features, stimuli-responsive drug delivery platforms have revolutionized the chemotherapy-based treatments with added benefits of enhanced bioavailability and selective cytotoxicity of cancer cells compared to the conventional modalities. The insensitivity of stimuli-responsive drug delivery platforms when exposed to normal cells prevents the release of cytotoxic drugs into the normal cells and therefore alleviates the off-target events associated with chemotherapy. Contrastingly, they showed amplified sensitivity and triggered release of chemotherapeutic payload when internalized into the tumor microenvironment causing maximum cytotoxic responses and the induction of cancer cell necrosis. This review focuses on the physical stimuli-responsive drug delivery systems and chemical stimuli-responsive drug delivery systems for triggered cancer chemotherapy through active and/or passive targeting. Moreover, the review also provided a brief insight into the molecular dynamic simulations associated with stimuli-based tumor targeting.

In vitro anti-leukemic assessment and sustained release behaviour of cytarabine loaded biodegradable polymer based nanoparticles.

AIMS: The study aimed to develop, characterize, and evaluate poly (ɛ-caprolactone) (PCL) based nanoparticles for the sustained release behaviour of cytarabine and to investigate the in vitro anti-cancer influence on KG-1 leukemic cell line. MATERIALS AND METHODS: Nanoprecipitation method was used for the preparation of cytarabine loaded PCL nanoparticles. The developed nanoparticles were characterized for physicochemical properties and the anti-leukemic effect on the KG-1 cell line was evaluated. KEY FINDINGS: A total number of five formulations were prepared with size range from 120.5 ± 1.18 to 341.5 ± 3.02, entrapment efficiency (41.31 ± 0.49 to 62.28 ± 0.39%), spherical morphology, negative zeta potentials, considerable particle size distribution, compatibility between the drug and excipients and thermal stability. X-ray diffraction analysis confirmed the successful incorporation of cytarabine in PCL polymer. In vitro drug release in phosphate buffer saline (pH 7.4) showed initial burst release followed by sustained release up to 48 h. The sustained release behaviour efficiently increased the toxicity of cytarabine-loaded PCL nanoparticles to KG-1 (leukemic) and MCF-7 (breast cancer) cell lines in time dependent manner with lower IC50 values than that of drug solution. The flow cytometry study revealed the better apoptotic activity of cytarabine loaded PCL nanoparticle against treated KG-1 cell line. The western blot analysis confirmed the upregulation of cleaved caspase-3 and downregulation of Bcl-2 protein. SIGNIFICANCE: The experimental results suggest that cytarabine loaded PCL nanoparticles is an efficient carrier to prevent the dose associated toxicity while providing sustained release pattern to ensure maximum anti-cancer influence.

Co-Delivery of Curcumin and Cisplatin to Enhance Cytotoxicity of Cisplatin Using Lipid-Chitosan Hybrid Nanoparticles.

BACKGROUND: Lipid-polymer hybrid nanoparticles (LPHNP) are suitable for co-delivery of hydrophilic and lipophilic drugs. The structural advantages of polymers and biomimetic properties of lipids enable higher encapsulation of drugs and controlled release profile. Lipid-polymer hybrid nanoparticles have been prepared for co-delivery of curcumin and cisplatin for enhanced cytotoxicity against ovarian cancer. MATERIAL AND METHODS: Chitosan, cisplatin, curcumin, Lipoid S75 were selected as structural components and ionic gelation method was used for preparation of LPHNPs. Nanoparticles were formed via ionic interaction of positively charged chitosan and negatively charged lipid. RESULTS: The optimized nanoparticles were of 225 nm with cationic charge. The encapsulation efficiency was greater than 80% with good drug loading. The drug release profile showed controlled release behavior of both curcumin and cisplatin simultaneously and the absence of burst release. The in vitro therapeutic efficacy and cellular association was evaluated using A2780 ovarian cell lines. To further investigate therapeutic efficacy, we developed 3D spheroids as tumor model to mimic the in vivo conditions. The cytotoxicity and uptake of co-loaded LPHNPs were evaluated on 3D spheroids and results indicated increased chemosensitization and enhanced therapeutic efficacy of co-loaded LPHNPs. CONCLUSION: Lipid-polymer hybrid nanoparticles could be a suitable platform for co-delivery of curcumin and cisplatin for enhanced cytotoxic effect on ovarian cell lines.