2D Janus carrier-enabled trojan horse: Gallium delivery for the sequential therapy of biofilm associated infection.

Biofilm-associated infections (BAIs) continue to pose a major challenge in the medical field. Nanomedicine, in particular, promises significant advances in combating BAIs through the introduction of a variety of nanomaterials and nano-antimicrobial strategies. However, studies to date have primarily focused on the removal of the bacterial biofilm and neglect the subsequent post-biofilm therapeutic measures for BAIs, rendering pure anti-biofilm strategies insufficient for the holistic recovery of affected patients. Herein, we construct an emerging dual-functional composite nanosheet (SiHx@Ga) that responds to pHs fluctuation in the biofilm microenvironment to enable a sequential therapy of BAIs. In the acidic environment of biofilm, SiHx@Ga employs the self-sensitized photothermal Trojan horse strategy to effectively impair the reactive oxygen species (ROS) defense system while triggering oxidative stress and lipid peroxidation of bacteria, engendering potent antibacterial and anti-biofilm effects. Surprisingly, in the post-treatment phase, SiHx@Ga adsorbs free pathogenic nucleic acids released after biofilm destruction, generates hydrogen with ROS-scavenging and promotes macrophage polarization to the M2 type, effectively mitigating damaging inflammatory burst and promoting tissue healing. This well-orchestrated strategy provides a sequential therapy of BAIs by utilizing microenvironmental variations, offering a conceptual paradigm shift in the field of nanomedicine anti-infectives.

Controlled Release of Molecules to Enhance Cell Survival and Regeneration.

Controlled release or controlled drug delivery comprises the set of techniques and approaches to improve bioavailability through improved safety and/or efficacy using a carrier material for the molecule of interest. The predictability and tunability of these carriers make them ideal for protection, localization, and sustained presentation of a wide range of therapeutics, including growth factors implicated in cell survival and regeneration. Here we provide a method for encapsulating epidermal growth factor in a degradable polymer matrix for delivery to the cornea. Additional notes are included to demonstrate the wide-ranging capabilities of such methods for other materials, therapeutic agents, and sites of action within the eye.

A versatile nanoplatform carrying cascade Pt nanozymes remodeling tumor microenvironment for amplified sonodynamic/chemo therapy of thyroid cancer.

Thyroid cancer is increasing globally, with anaplastic thyroid carcinoma (ATC) being the most aggressive type and having a poor prognosis. Current clinical treatments for thyroid cancer present numerous challenges, including invasiveness and the necessity of lifelong medication. Furthermore, a significant portion of patients with ATC experience cancer recurrence and metastasis. To overcome this dilemma, we developed a pH-responsive biomimetic nanocarrier (CLP@HP-A) through the incorporation of Chlorin e6 (Ce6) and Lenvatinib (Len) within hollow polydopamine nanoparticles (HP) that were further modified with platinum nanoparticles (Pt), enabling synergistic chemotherapy and sonodynamic therapy. The CLP@HP-A nanocarriers exhibited specific binding with galectin-3 receptors, facilitating their internalization through receptor-mediated endocytosis for targeted drug delivery. Upon exposure to ultrasound (US) irradiation, Ce6 rapidly generated reactive oxygen species (ROS) to induce significant oxidative stress and trigger apoptosis in tumor cells. Additionally, Pt not only alleviated tumor hypoxia by catalyzing the conversion of H2O2 to oxygen (O2) but also augmented intracellular ROS levels through the production of hydroxyl radicals (•OH), thereby enhancing the efficacy of sonodynamic therapy. Moreover, Len demonstrated a potent cytotoxic effect on thyroid cancer cells through the induction of apoptosis. Transcriptomics analysis findings additionally corroborated that CLP@HP-A effectively triggered cancer cell apoptosis, thereby serving as a crucial mechanism for its cytotoxic effects. In conclusion, the integration of sonodynamic/chemo combination therapy with targeted drug delivery systems offers a novel approach to the management of malignant tumors.

Tumor-targeted delivery of hyaluronic acid/polydopamine-coated Fe2+-doped nano-scaled metal-organic frameworks with doxorubicin payload for glutathione depletion-amplified chemodynamic-chemo cancer therapy.

Chemodynamic therapy (CDT), an emerging cancer treatment modality, uses multivalent metal elements to convert endogenous hydrogen peroxide (H2O2) to toxic hydroxyl radicals (•OH) via a Fenton or Fenton-like reaction, thus eliciting oxidative damage of cancer cells. However, the antitumor potency of CDT is largely limited by the high glutathione (GSH) concentration and low catalytic efficiency in the tumor sites. The combination of CDT with chemotherapy provides a promising strategy to overcome these limitations. In this work, to enhance antitumor potency by tumor-targeted and GSH depletion-amplified chemodynamic-chemo therapy, the hyaluronic acid (HA)/polydopamine (PDA)-decorated Fe2+-doped ZIF-8 nano-scaled metal-organic frameworks (FZ NMs) were fabricated and utilized to load doxorubicin (DOX), a chemotherapy drug, via hydrophobic, π-π stacking and charge interactions. The attained HA/PDA-covered DOX-carrying FZ NMs (HPDFZ NMs) promoted DOX and Fe2+ release in weakly acidic and GSH-rich milieu and exhibited acidity-activated •OH generation. Through efficient CD44-mediated endocytosis, the HPDFZ NMs internalized by CT26 cells not only prominently enhanced •OH accumulation by consuming GSH via PDA-mediated Michael addition combined with Fe2+/Fe3+ redox couple to cause mitochondria damage and lipid peroxidation, but also achieved intracellular DOX release, thus eliciting apoptosis and ferroptosis. Importantly, the HPDFZ NMs potently inhibited CT26 tumor growth in vivo at a low DOX dose and had good biosafety, thereby showing promising potential in tumor-specific treatment.

Cubosome lipid nanocarriers for delivery of ultra-short antimicrobial peptides.

HYPOTHESIS: Although antimicrobial peptides (AMPs) are a promising class of new antibiotics, their inherent susceptibility to degradation requires nanocarrier-mediated delivery. While cubosome nanocarriers have been extensively studied for delivery of AMPs, we do not currently understand why cubosome encapsulation improves antimicrobial efficacy for some compounds but not others. This study therefore aims to investigate the link between the mechanism of action and permeation efficiency of the peptides, their encapsulation efficacy, and the antimicrobial activity of these systems. EXPERIMENTS: Encapsulation and delivery of Indolicidin, and its ultra-short derivative, Priscilicidin, were investigated using SAXS, cryo-TEM and circular dichroism. Molecular dynamics simulations were used to understand the loading of these peptides within cubosomes. The antimicrobial efficacy was assessed against gram-negative (E. coli) and gram-positive (MRSA) bacteria. FINDINGS: A high ionic strength solution was required to facilitate high loading of the cationic AMPs, with bilayer encapsulation driven by tryptophan and Fmoc moieties. Cubosome encapsulation did not improve the antimicrobial efficacy of the AMPs consistent with their high permeation, as explained by a recent 'diffusion to capture model'. This suggests that cubosome encapsulation may not be an effective strategy for all antimicrobial compounds, paving the way for improved selection of nanocarriers for AMPs, and other antimicrobial compounds.

Oral formulations for highly lipophilic drugs: Impact of surface decoration on the efficacy of self-emulsifying drug delivery systems.

AIM: To evaluate the impact of the surface decoration of cannabidiol (CBD) loaded self-emulsifying drug delivery systems (SEDDS) on the efficacy of the formulations to cross the various barriers faced by orally administered drugs. METHODS: Polyethylene glycol (PEG)-free polyglycerol (PG)-based SEDDS, mixed zwitterionic phosphatidyl choline (PC)/PEG-containing SEDDS and PEG-based SEDDS were compared regarding stability against lipid degrading enzymes, surface properties, permeation across porcine mucus, cellular uptake and cytocompatibility. RESULTS: SEDDS with a size of about 200 nm with narrow size distributions were developed and loaded with 20-21 % of CBD. For PG containing PEG-free SEDDS increased degradation by lipid degrading enzymes was observed compared to PEG-containing formulations. The surface hydrophobicity of placebo SEDDS increased in the order of PG-based to mixed PC/PEG-based to PEG-based SEDDS. The influence of this surface hydrophobicity was also observed on the ability of the SEDDS to cross the mucus gel layer where highest mucus permeation was achieved for most hydrophobic PEG-based SEDDS. Highest cellular internalization was observed for PEG-based Lumogen Yellow (LY) loaded SEDDS with 92 % in Caco-2 cells compared to only 30 % for mixed PC/PEG-based SEDDS and 1 % for PG-based SEDDS, leading to a 100-fold improvement in cellular uptake for SEDDS having highest surface hydrophobicity. For cytocompatibility all developed placebo SEDDS showed similar results with a cell survival of above 75 % for concentrations below 0.05 % on Caco-2 cells. CONCLUSION: Higher surface hydrophobicity of SEDDS to orally deliver lipophilic drugs as CBD seems to be a promising approach to increase the intracellular drug concentration by an enhanced permeation through the mucus layer and cellular internalization.

Lipidic drug delivery systems are responsive to the human microbiome.

In vitro and in vivo tests for therapeutic agents are typically conducted in sterile environments, but many target areas for drug delivery are home to thousands of microbial species. Here, we examine the behaviour of lipidic nanomaterials after exposure to representative strains of four bacterial species found in the gastrointestinal tract and skin. Small angle X-ray scattering measurements show that the nanostructure of monoolein cubic and inverse hexagonal phases are transformed, respectively, into inverse hexagonal and inverse micellar cubic phases upon exposure to a strain of live Staphylococcus aureus often present on skin and mucosa. Further investigation demonstrates that enzymatic hydrolysis and cell membrane lipid transfer are both likely responsible for this effect. The structural responses to S. aureus are rapid and significantly reduce the rate of drug release from monoolein-based nanomaterials. These findings are the first to demonstrate how a key species in the live human microbiome can trigger changes in the structure and drug release properties of lipidic nanomaterials. The effect appears to be strain specific, varies from patient to patient and body region to body region, and is anticipated to affect the bioapplication of monoglyceride-based formulations.

Surface engineering of metal-organic framework nanoparticles-based miRNA carrier: Boosting RNA stability, intracellular delivery and synergistic therapy.

MicroRNAs (miRNAs) are small noncoding RNAs that are critical for the regulation of multiple physiological and pathological processes, thus holding great clinical potential. However, the therapeutic applications of miRNAs are severely limited by their biological instability and poor intracellular delivery. Herein, we describe a dual-layers surface engineering strategy to design an efficient miRNA delivery nanosystem based on metal-organic frameworks (MOFs) incorporating lipid coating. The resulting nanoparticle system was demonstrated to protect miRNA from ribonuclease degradation, enhance cellular uptake and facilitate lysosomal escape. These ensured effective miRNA mediated gene therapy, which synergized with MOF-specific photodynamic therapy and pre-encapsulated doxorubicin (Dox) chemotherapy to provide a multifunctional with therapeutic effectiveness against cencer cells The mechanisms of miRNA binding and Dox loading were revealed, demonstrating the potential of the present MOFs surface-engineered strategy to overcome their inherent pore-size restriction for macromolecular miRNA carrying, enableefficient co-delivery. In vitro studies revealed the potential of our multifunctional system for miRNA delivery and the demonstrated the therapeutic effectiveness against cancer cells, thereby providing a versatile all-in-one MOFs strategy for delivery of nucleic acids and diverse therapeutic molecules in synergistic therapy.

A computer-aided, heterodimer-based "triadic" carrier-free drug delivery platform to mitigate multidrug resistance in lung cancer and enhance efficiency.

Co-delivering multiple drugs or circumventing the drug efflux mechanism can significantly decrease multidrug resistance (MDR), a major cause of cancer treatment failure. In this study, we designed and fabricated a universal "three-in-one" self-delivery system for synergistic cancer therapy using a computer-aided strategy. First, we engineered two glutathione (GSH)-responsive heterodimers, ERL-SS-CPT (erlotinib [ERL] linked with camptothecin [CPT] via a disulfide bond [SS]) and CPT-SS-ERI (CPT conjugated with erianin [ERI]), which serve as both cargo and carrier material. Next, molecular dynamics simulations indicated that multiple noncovalent molecular forces, including π-π stacking, hydrogen bonds, hydrophobic interactions, and sulfur bonds, drive the self-assembly process of these heterodimers. We then explored the universality of the heterodimers and developed a "triadic" drug delivery platform comprising 40 variants. Subsequently, we conducted case studies on docetaxel (DTX)-loaded ERL-SS-CPT nanoparticles (denoted as DTX@ERL-SS-CPT NPs) and curcumin (CUR)-loaded ERL-SS-CPT NPs (identified as CUR@CPT-SS-ERI NPs) to comprehensively investigate their self-assembly mechanism, physicochemical properties, storage stability, GSH-responsive drug release, cellular uptake, apoptosis effects, biocompatibility, and cytotoxicity. Both NPs exhibited well-defined spherical structures, high drug loading rates, and excellent storage stability. DTX@ERL-SS-CPT NPs exhibited the strongest cytotoxicity in A549 cells, following the order of DTX@ERL-SS-CPT NPs > ERL-SS-CPT NPs > CPT > DTX > ERL. Conversely, DTX@ERL-SS-CPT NPs showed negligible cytotoxicity in normal human bronchial epithelium cell line (BEAS-2B), indicating good biocompatibility and safety. Similar observations were made for CUR@CPT-SS-ERI NPs regarding biocompatibility and cytotoxicity. Upon endocytosis and encountering intracellular overexpressed GSH, the disulfide-bond linker is cleaved, resulting in the release of the versatile NPs into three parts. The spherical NPs enhance water solubility, reduce the required dosage of free drugs, and increase cellular drug accumulation while suppressing P-glycoprotein (P-gp) expression, leading to apoptosis. This work provides a computer-aided universal strategy-a heterodimer-based "triadic" drug delivery platform-to enhance anticancer efficiency while reducing multidrug resistance.

Current Review on Nanophytomedicines in the Treatment of Oral Cancer: Recent Trends and Treatment Prospects.

Cancer is one of the major life-threatening diseases in the world and oral cancer is the 8th most common type of deadly cancers in Asian countries. Despite many causes, tobacco is the main causative agent as 90% of oral cancer cases were due to daily consumption of tobacco and its products. The major drawback of the conventional therapies for oral cancer including chemotherapy, surgery and radiotherapy or combination of these is the dose limiting toxicity. Developments in technology and research led to new innovative discoveries in cancer treatments. In the past few decades, increased attention has been given to researches in alternative cancer treatment strategies using plants and plant products. Recently many anticancer drugs from natural products or phytochemicals were approved internationally. Due to the low bioavailability and poor solubility of phytochemicals, various research works on nano-carrier based drug delivery systems were exploited in the recent past to make them as promising anticancer agents. In the current review, an overview of oral cancer and its treatment, risk factors, missing links of conventional therapies, contribution of nanotechnology in cancer treatment and research on phytochemical based drug treatment and different polymeric nanoparticles were discussed briefly. The future prospects for the use of various types of polymeric nanoparticles applied in the diagnosis and treatment of oral cancer were also mentioned. The major concern of this review is to give the reader a better understanding on various types of treatment for oral cancer.

Nanobiocatalysis: Approach and Applications in Drug Development and Sensing.

Enzymes play a pivotal role in the human body, but their potential is not limited to just that. Scientists have successfully modified these enzymes as nanobiocatalysts or nanozymes for industrial or commercial use, either in the food, medicine, biotech or even textile industries. These nanobiocatalysts and nanozymes offer several advantages over enzymes, like better stability, improved shelf-life, increased percentage yield, and reuse potential, which is very difficult with normal enzymes. The various techniques of NBC synthesis using immobilization techniques like adsorption, covalent binding, affinity immobilization, and entrapment methods are briefly discussed. The enzymes are either entrapped or adsorbed on the nanocarrier matrices, which can be nanofibers, nanoporous carriers, or nanocontainers as nanobiocatalysts. We also highlight the challenges the nanobiocatalyst overcomes in the industrial production of some drugs like sitagliptin, montelukast, pregabalin, and atorvastatin. Also, the inactivation of an organophosphate or opioid poisoning treating agent, SSOPOX nanohybrid, is discussed in this paper. Nanozymes are intrinsic enzyme-like compounds, and they also show wide application in themselves. Their GQD/AGNP nanohybrid shows antibacterial potential; they can also be utilized in optical sensing to detect small molecules, ions, nucleic acids, proteins, and cancer cells. In this paper, various applications of these NBCs have been discussed, and their potential applications with examples are also mentioned. Nanoenzymes can address targeted drug delivery via the controlled release of drugs to increase the efficacy of anticancer drugs that minimize damage to healthy tissue or cells.

Oral delivery of Sunitinib malate using carboxymethyl cellulose/poly(acrylic acid-itaconic acid)/Cloisite 30B nanocomposite hydrogel as a pH-responsive carrier.

This work aimed to fabricate a Cloisite 30B-incorporated carboxymethyl cellulose graft copolymer of acrylic acid and itaconic acid hydrogel (Hyd) via a free radical polymerization method for controlled release of Sunitinib malate anticancer drug. The synthesized samples were characterized by FTIR, XRD, TEM, and SEM-dot mapping analyses. The encapsulation efficiency of Hyd and Hyd/Cloisite 30B (6 wt%) was 81 and 93%, respectively, showing the effectiveness of Cloisite 30B in drug loading. An in vitro drug release study showed that drug release from all samples in a buffer solution with pH 7.4 was higher than in a buffer solution with pH 5.5. During 240 min, the cumulative drug release from Hyd/Cloisite 30B (94.97% at pH 7.4) is lower than Hyd (53.71% at pH 7.4). Also, drug-loaded Hyd/Cloisite 30B (6 wt%) demonstrated better antibacterial activity towards S. Aureus bacteria and E. Coli. High anticancer activity of Hyd/Cloisite 30B against MCF-7 human breast cancer cells was shown by the MTT assay, with a MCF-7 cell viability of 23.82 ± 1.23% after 72-hour incubation. Our results suggest that Hyd/Cloisite 30B could be used as a pH-controlled carrier to deliver anticancer Sunitinib malate.

Enteral Route Nanomedicine for Cancer Therapy.

With the in-depth knowledge of the pathological and physiological characteristics of the intestinal barrier-portal vein/intestinal lymphatic vessels-systemic circulation axis, oral targeted drug delivery is frequently being renewed. With many advantages, such as high safety, convenient administration, and good patient compliance, many researchers have begun to explore targeted drug delivery from intravenous injections to oral administration. Over the past few decades, the fields of materials science and nanomedicine have produced various drug delivery platforms that hold great potential in overcoming the multiple barriers associated with oral drug delivery. However, the oral transport of particles into the systemic circulation is extremely difficult due to immune rejection and biochemical invasion in the intestine, which limits absorption and entry into the bloodstream. The feasibility of the oral delivery of targeted drugs to sites outside the gastrointestinal tract (GIT) is unknown. This article reviews the biological barriers to drug absorption, the in vivo fate and transport mechanisms of drug carriers, the theoretical basis for oral administration, and the impact of carrier structural evolution on oral administration to achieve this goal. Finally, this article reviews the characteristics of different nano-delivery systems that can enhance the bioavailability of oral therapeutics and highlights their applications in the efficient creation of oral anticancer nanomedicines.

Docetaxel-tethered di-Carboxylic Acid Derivatised Fullerenes: A Promising Drug Delivery Approach for Breast Cancer.

Docetaxel (DTX) has become widely accepted as a first-line treatment for metastatic breast cancer; however, the frequent development of resistance provides challenges in treating the disease.C60 fullerene introduces a unique molecular form of carbon, exhibiting attractive chemical and physical properties. Our study aimed to develop dicarboxylic acid-derivatized C60 fullerenes as a novel DTX delivery carrier. This study investigated the potential of water-soluble fullerenes to deliver the anti-cancer drug DTX through a hydrophilic linker. The synthesis was carried out using the Prato reaction. The spectroscopic analysis confirmed the successful conjugation of DTX molecules over fullerenes. The particle size of nanoconjugate was reported to be 122.13 ± 1.63 nm with a conjugation efficiency of 76.7 ± 0.14%. The designed conjugate offers pH-dependent release with significantly less plasma pH, ensuring maximum release at the target site. In-vitro cell viability studies demonstrated the enhanced cytotoxic nature of the developed nanoconjugate compared to DTX. These synthesized nanoscaffolds were highly compatible with erythrocytes, indicating the safer intravenous route administration. Pharmacokinetic studies confirmed the higher bioavailability (~ 6 times) and decreased drug clearance from the system vis-à-vis plain drug. The histological studies reveal that nanoconjugate-treated tumour cells exhibit similar morphology to normal cells. Therefore, it was concluded that this developed formulation would be a valuable option for clinical use.

Prolonged Skin Retention of Luliconazole from SLNs Based Topical Gel Formulation Contributing to Ameliorated Antifungal Activity.

The development of effective therapy is necessary because the patients have to contend with long-term therapy as skin fungal infections usually relapse and are hardly treated. Despite being a potent antifungal agent, luliconazole (LCZ) has certain shortcomings such as limited skin penetration, low solubility in aqueous medium, and poor skin retention. Solid Lipid Nanoparticles (SLNs) were developed using biodegradable lipids by solvent injection method and were embodied into the gel base for topical administration. After in-vitro characterizations of the formulations, molecular interactions of the drug with excipients were analyzed using in-silico studies. Ex-vivo release was determined in contrast to the pure LCZ and the commercial formulation followed by in-vivo skin localization, skin irritation index, and antifungal activity. The prepared SLNs have an average particle size of 290.7 nm with no aggregation of particles and homogenous gels containing SLNs with ideal rheology and smooth texture properties were successfully prepared. The ex-vivo LCZ release from the SLN gel was lower than the commercial formulation whereas its skin deposition and skin retention were higher as accessed by CLSM studies. The drug reaching the systemic circulation and the skin irritation potential were found to be negligible. The solubility and drug retention in the skin were both enhanced by the development of SLNs as a carrier. Thus, SLNs offer significant advantages by delivering long lasting concentrations of LCZ at the site of infection for a complete cure of the fungal load together with skin localization of the topical antifungal drug.

"Enhancing Oral Drug Absorption: Overcoming Physiological and Pharmaceutical Barriers for Improved Bioavailability".

The oral route stands out as the most commonly used method for drug administration, prized for its non-invasive nature, patient compliance, and easy administration. Several elements influence the absorption of oral medications, including their solubility, permeability across mucosal membranes, and stability within the gastrointestinal (GI) environment. Research has delved into comprehending physicochemical, biochemical, metabolic, and biological obstacles that impact the bioavailability of a drug. To improve oral drug absorption, several pharmaceutical technologies and delivery methods have been studied, including cyclodextrins, micelles, nanocarriers, and lipid-based carriers. This review examines both traditional and innovative drug delivery methods, as well as the physiological and pharmacological barriers influencing medication bioavailability when taken orally. Additionally, it describes the challenges and advancements in developing formulations suitable for oral use.

Revolutionizing Brain Drug Delivery: Buccal Transferosomes on the Verge of a Breakthrough.

The buccal cavity, also known as the oral cavity, is a complex anatomical structure that plays a crucial role in various physiological processes. It serves as a gateway to the digestive system and facilitates the initial stages of food digestion and absorption. However, its significance extends beyond mere digestion as it presents a promising route for drug delivery, particularly to the brain. Transferosomes are lipid-based vesicles that have gained significant attention in the field of drug delivery due to their unique structure and properties. These vesicles are composed of phospholipids that form bilayer structures capable of encapsulating both hydrophilic and lipophilic drugs. Strategies for the development of buccal transferosomes for brain delivery have emerged as promising avenues for pharmaceutical research. This review aims to explore the various approaches and challenges associated with harnessing the potential of buccal transferosomes as a means of enhancing drug delivery to the brain. By understanding the structure and function of both buccal tissue and transferosomes, researchers can develop effective formulation methods and characterization techniques to optimize drug delivery. Furthermore, strategic approaches and success stories in buccal transferosome development are highlighted, showcasing inspiring examples that demonstrate their potential to revolutionize brain delivery.

Cytotoxic Impact of Naringenin-Loaded Solid Lipid Nanoparticles on RIN5F Pancreatic ß Cells via Autophagy Blockage.

BACKGROUND: Autophagy plays a crucial role in modulating the proliferation of cancer diseases. However, the application of Naringenin (Nar), a compound with potential benefits against these diseases, has been limited due to its poor solubility and bioavailability. OBJECTIVE: This study aimed to develop solid lipid nanoparticles (Nar-SLNs) loaded with Nar to enhance their therapeutic impact. METHODS: In vitro experiments using Rin-5F cells exposed to Nar and Nar-SLNs were carried out to investigate the protective effects of Nar and its nanoformulation against the pancreatic cancer cell line of Rin-5F. RESULTS: Treatment with Nar and Nar-SLN led to an increase in autophagic markers (Akt, LC3, Beclin1, and ATG genes) and a decrease in the level of miR-21. Both Nar and Nar-SLN treatments inhibited cell proliferation and reduced the expression of autophagic markers. Notably, Nar-SLNs exhibited greater efficacy compared to free Nar. CONCLUSION: These findings suggest that SLNs effectively enhance the cytotoxic impact of Nar, making Nar-SLNs a promising candidate for suppressing or preventing Rin-5F cell growth.

Nanocarriers for Cannabinoid Delivery: Enhancing Therapeutic Potential.

Medical cannabis has potential therapeutic benefits in managing pain, anxiety, depression, and neurological and movement disorders. Phytocannabinoids derived from the cannabis plant are responsible for their pharmacological and therapeutic properties. However, the complexity of cannabis components, especially cannabinoids, poses a challenge to effective medicinal administration. Even with the increasing acceptance of cannabis-based medicines, achieving consistent bioavailability and targeted distribution remains difficult. Conventional administration methods are plagued by solubility and absorption problems requiring innovative solutions. After conducting a thorough review of research papers and patents, it has become evident that nanotechnology holds great promise as a solution. The comprehensive review of 36 research papers has yielded valuable insights, with 7 papers reporting enhanced bioavailability, while others have focused on improvements in release, solubility, and stability. Additionally, 19 patents have been analyzed, of which 7 specifically claim enhanced bioavailability, while the remaining patents describe various formulation methods. These patents outline effective techniques for encapsulating cannabis using nanocarriers, effectively addressing solubility and controlled release. Studies on the delivery of cannabis using nanocarriers focus on improving bioavailability, prolonging release, and targeting specific areas. This synthesis highlights the potential of nanotechnology to enhance cannabis therapies and pave the way for innovative interventions and precision medicine.

Polymeric nanocarrier via metabolism regulation mediates immunogenic cell death with spatiotemporal orchestration for cancer immunotherapy.

The limited efficacy of cancer immunotherapy occurs due to the lack of spatiotemporal orchestration of adaptive immune response stimulation and immunosuppressive tumor microenvironment modulation. Herein, we report a nanoplatform fabricated using a pH-sensitive triblock copolymer synthesized by reversible addition-fragmentation chain transfer polymerization enabling in situ tumor vaccination and tumor-associated macrophages (TAMs) polarization. The nanocarrier itself can induce melanoma immunogenic cell death (ICD) via tertiary amines and thioethers concentrating on mitochondria to regulate metabolism in triggering endoplasmic reticulum stress and upregulating gasdermin D for pyroptosis as well as some features of ferroptosis and apoptosis. After the addition of ligand cyclic arginine-glycine-aspartic acid (cRGD) and mannose, the mixed nanocarrier with immune adjuvant resiquimod encapsulation can target B16F10 cells for in situ tumor vaccination and TAMs for M1 phenotype polarization. In vivo studies indicate that the mixed targeting nanoplatform elicits tumor ICD, dendritic cell maturation, TAM polarization, and cytotoxic T lymphocyte infiltration and inhibits melanoma volume growth. In combination with immune checkpoint blockade, the survival time of mice is markedly prolonged. This study provides a strategy for utilizing immunoactive materials in the innate and adaptive immune responses to augment cancer therapy.