Increased Drug Permeation Research Articles

Rosuvastatin Flexible Chitosomes: Development, In Vitro Evaluation and Enhancement of Anticancer Efficacy Against HepG2 and MCF7 Cell Lines.

Rosuvastatin (ROS), a statin drug with promising anticancer properties has a low bioavailability of approximately 20% due to lipophilicity and first-pass metabolism. This study aimed to enhance ROS anticancer efficacy through loading into flexible chitosomes. The chitosomes were prepared starting from negatively charged liposomes through electrostatic interactions with chitosan. The conversion of zeta potential from negative to positive confirmed the successful formation of chitosomes. The chitosan coating increased the particle size and zeta potential, which ranged from 202.0 ± 1.7nm to 504.7 ± 25.0nm and from - 44.9 ± 3.0 mV to 50.1 ± 2.6 mV, respectively. Chitosan and drug concentrations had an important influence on the chitosome properties. The optimum chitosome formulation was used to prepare ROS-loaded flexible chitosomes using different concentrations of four edge activators. The type and concentration of edge activator influenced the particle size, drug entrapment efficiency, and drug release rate of the flexible chitosomes. Flexible chitosomes significantly increased drug permeation through rat abdominal skin compared to control transferosomes and drug solution. The optimal ROS flexible chitosomes containing sodium deoxycholate as an edge activator had a 2.23-fold increase in ROS cytotoxic efficacy against MCF7 cells and a 1.84-fold increase against HepG2 cells. These results underscore the potential of flexible chitosomes for enhancing ROS anticancer efficacy.

Strategic development of aceclofenac loaded organosomes for topical application: An explorative ex-vivo and in-vivo investigation for arthritis

Present study intends to develop aceclofenac-encapsulated organosomes (OS), which consist of phospholipids coupled with a combination of organic solvents, for the management of arthritis. The formulation was characterized and tested for efficacy using formalin-induced hyperalgesia, air pouch, and CFA-induced arthritic rat models. OS system exhibited spherical dimension, nanometric size with low PDI (278.3 ± 12.21 nm; 0.145), zeta potential (−24.56 ± 7.53 mV), drug entrapment (85.62 ± 7.2 %) and vesicles count (4.2x104 mm3). The gelled OS formulation demonstrated increased drug permeability and accumulation rate (51.77 ± 7.1 % and 396.19 ± 59.21 µg/cm2) compared to the MKT product (102.93 ± 13.78 µg/cm2 and 16.14 ± 4.3 %). Dermatokinetic assessments exhibited significantly higher drug levels in dermal layers compared to MKT product (p < 0.001), and CLSM studies further supported the OS system’s deeper penetration. The results of arthritic index significantly better (9 times) in the OS-treated group than the MKT product. OS system treatment significantly reduced biochemicals and cytokines levels, such as CRP, ESR, TLC, lymphocytes, TNF-α, IL-6, and IL-1β to levels of the control group (p < 0.001). Pseudoplastic behaviour of the developed product was indicated by the rheological results, and it also demonstrated biocompatibility through skin compliance studies. Based on the current findings, it appears that OS may be a better choice for managing arthritis and related inflammations.

In Vitro Drug Delivery through the Blood–Brain Barrier Using Cold Atmospheric Plasma

This study explores the potential of cold atmospheric plasma (CAP) to facilitate the delivery of large-molecule drugs to the brain. The blood–brain barrier (BBB) restricts the passage of most drugs, hindering treatment for neurological disorders. CAP generates reactive oxygen and nitrogen species (RONS) that may disrupt the BBB’s tight junctions, potentially increasing drug permeability. An in vitro BBB model and an immortalized cell line (bEND.3) were used in this experiment. Fluorescein isothiocyanate dextran (FD-4), a model drug, was added to the cells to determine drug permeability. Custom microplasma was used to produce reactive oxygen species (ROS). Trans-endothelial electrical resistance (TEER) measurements assessed the integrity of the BBB after the CAP treatment. A decrease in TEER was observed in the CAP-treated group compared to the controls, suggesting increased permeability. Additionally, fluorescence intensity measurements from the basal side of the trans-well plate indicated higher drug passage in the CAP-treated group. Moreover, the higher presence of ROS in the plasma-treated cells confirmed the potential of CAP in drug delivery. These findings suggest that CAP may be a promising approach for enhancing brain drug delivery.

Optimisation and in-vivo evaluation of extracted Karanjin loaded liposomal topical formulation for treatment of psoriasis in tape-stripped mouse model

Aim The present work is focus on development of anti-psoriasis activity of Karanjin (isolated from Pongamia pinnata seed oil) loaded liposome based lotion for enhancement of skin permeation and retention. Method Karanjin was isolated using liquid-liquid extraction method and characterised by HPLC analysis and partition coefficient. Further, isolated Karanjin was loaded into liposomes using thin-film hydration technique and optimised by Box-Behnken design. Selected optimised batch was characterised their mean diameter, PDI, zeta potential, and entrapment efficiency, morphology (by TEM), FTIR and ex-vivo skin retention. Additionally, Karanjin loaded liposomes were formulated into lotion and characterise their rheological, spreadability, texture, ex-vivo skin permeation & retention, stability and anti-psoriatic activity in mouse tail model. Result The yield of Karanjin from seed oil was 0.1% w/v and have lipophilic nature. The optimised liposomal formulation showed 195 ± 1.8 nm mean diameter, 0.271 ± 0.02 PDI, −27.0 ± 2.1 mV zeta potential and 61.97 ± 2.5% EE. TEM image revel the spherical shap of liposome surrounded by single phospholipid bilayer and no interection between drug and excipients. Further, lotion was prepared by 0.1% w/v carbopol and found to 615 mPa.sec viscosity, good thixotropic behaviour, spreadability and texture. There was 22.44% increase in drug permeation for Karanjin loaded liposomal lotion compared to pure Karanjin lotion, confirm by ex-vivo permeation and retention. While, in-vivo study revel the liposomal lotion of Karanjin was found to have 16.09% higher drug activity then 5% w/w conventional Karanjin lotion. Conclusion Karanjin loaded liposomal lotion have an effective anti-psoriatic agent and showed better skin permeation and retention than the conventional Karanjin lotion.

Verapamil-Loaded Cubosomes for Enhancing Intranasal Drug Delivery: Development, Characterization, Ex Vivo Permeation, and Brain Biodistribution Studies

Verapamil hydrochloride (VRP), an antihypertensive calcium channel blocker drug has limited bioavailability and short half-life when taken orally. The present study was aimed at developing cubosomes containing VRP for enhancing its bioavailability and targeting to brain for cluster headache (CH) treatment as an off-label use. Factorial design was conducted to analyze the impact of different components on entrapment efficiency (EE%), particle size (PS), zeta potential (ZP), and percent drug release. Various in-vitro characterizations were performed followed by pharmacokinetic and brain targeting studies. The results revealed the significant impact of glyceryl monooleate (GMO) on increasing EE%, PS, and ZP of cubosomes with a negative influence on VRP release. The remarkable effect of Poloxamer 407 (P407) on decreasing EE%, PS, and ZP of cubosomes was observed besides its influence on accelerating VRP release%. The DSC thermograms indicated the successful entrapment of the amorphous state of VRP inside the cubosomes. The design suggested an optimized formulation containing GMO (50% w/w) and P407 (5.5% w/w). Such formulation showed a significant increase in drug permeation through nasal mucosa with high Er value (2.26) when compared to VRP solution. Also, the histopathological study revealed the safety of the utilized components used in the cubosomes preparation. There was a significant enhancement in the VRP bioavailability when loaded in cubosomes owing to its sustained release favored by its direct transport to brain. The I.N optimized formulation had greater BTE% and DTP% at 183.53% and 90.19%, respectively in comparison of 41.80% and 59% for the I.N VRP solution.Graphical

Fluconazole-Loaded Ibuprofen In Situ Gel-Based Oral Spray for Oropharyngeal Candidiasis Treatment.

Oral candidiasis is a fungal infection affecting the oral mucous membrane, and this research specifically addresses on a localized treatment through fluconazole-loaded ibuprofen in situ gel-based oral spray. The low solubility of ibuprofen is advantageous for forming a gel when exposed to an aqueous phase. The 1% w/w fluconazole-loaded in situ gel oral sprays were developed utilizing various concentrations of ibuprofen in N-methyl pyrrolidone. The prepared solutions underwent evaluation for viscosity, surface tension, contact angle, water tolerance, gel formation, interface interaction, drug permeation, and antimicrobial studies. The higher amount of ibuprofen reduced the surface tension and retarded solvent exchange. The use of 50% ibuprofen as a gelling agent demonstrated prolonged drug permeation for up to 24h. The incorporation of Cremophor EL in the formulations resulted in increased drug permeation and exhibited effective inhibition against Candida albicans, Candida krusei, Candida lusitaniae, and Candida tropicalis. While the Cremophor EL-loaded formulation did not exhibit enhanced antifungal effects on agar media, its ability to facilitate the permeation of fluconazole and ibuprofen suggested potential efficacy in countering Candida invasion in the oral mucosa. Moreover, these formulations demonstrated significant thermal inhibition of protein denaturation in egg albumin, indicating anti-inflammatory properties. Consequently, the fluconazole-loaded ibuprofen in situ gel-based oral spray presents itself as a promising dosage form for oropharyngeal candidiasis treatment.

Lack of Effect of Antioxidants on Biopharmaceutics Classification System (BCS) Class III Drug Permeability

The addition of antioxidants to pharmaceutical products is a potential approach to inhibit nitrosamine formation, particularly in solid oral dosage forms like tablets and capsules. The objective was to assess the effect of ten antioxidants on the permeability of four Biopharmaceutics Classification System (BCS) Class III drugs. Bi-directional drug permeability studies in the absence and presence of antioxidants were performed in vitro across MDCK-II monolayers. No antioxidant increased drug permeability, while the positive control sodium lauryl sulfate always increased drug permeability. Results support that any of the ten antioxidants, up to at least 10 mg, can be added to a solid oral dosage form without modulating passive drug intestinal permeability. Additional considerations are also discussed.

Nanoparticle-Based Combinational Strategies for Overcoming the Blood-Brain Barrier and Blood-Tumor Barrier.

The blood-brain barrier (BBB) and blood-tumor barrier (BTB) pose substantial challenges to efficacious drug delivery for glioblastoma multiforme (GBM), a primary brain tumor with poor prognosis. Nanoparticle-based combinational strategies have emerged as promising modalities to overcome these barriers and enhance drug penetration into the brain parenchyma. This review discusses various nanoparticle-based combinatorial approaches that combine nanoparticles with cell-based drug delivery, viral drug delivery, focused ultrasound, magnetic field, and intranasal drug delivery to enhance drug permeability across the BBB and BTB. Cell-based drug delivery involves using engineered cells as carriers for nanoparticles, taking advantage of their intrinsic migratory and homing capabilities to facilitate the transport of therapeutic payloads across BBB and BTB. Viral drug delivery uses engineered viral vectors to deliver therapeutic genes or payloads to specific cells within the GBM microenvironment. Focused ultrasound, coupled with microbubbles or nanoparticles, can temporarily disrupt the BBB to increase drug permeability. Magnetic field-guided drug delivery exploits magnetic nanoparticles to facilitate targeted drug delivery under an external magnetic field. Intranasal drug delivery offers a minimally invasive avenue to bypass the BBB and deliver therapeutic agents directly to the brain via olfactory and trigeminal pathways. By combining these strategies, synergistic effects can enhance drug delivery efficiency, improve therapeutic efficacy, and reduce off-target effects. Future research should focus on optimizing nanoparticle design, exploring new combination strategies, and advancing preclinical and clinical investigations to promote the translation of nanoparticle-based combination therapies for GBM.

Reshaping antibiotic delivery: Chitosan‐based polymeric hydrogel for transdermal treatment of drug resistant bacteria

AbstractThe aim of the present study was to formulate and assess the antibacterial efficacy of a transdermal chitosan based polymeric hydrogel for transdermal treatment of bacterial resistance strains. Utilizing the micro‐emulsion method and the Box–Behnken design model, imipenem‐cilastatin (IMI‐CIL) loaded nanostructured lipid carriers (NLCs) were fabricated and optimized, employing Compritol 888 ATO as the lipid core and Tween 80 as the stabilizer. The optimized nanoformulation underwent a comprehensive evaluation encompassing parameters such as particle diameter, zeta potential, surface morphology, entrapment efficiency, crystallinity, and molecular interaction. The optimized nanoparticles displayed a mean particle size of 129 nm, a zeta potential of −19.8 mV, and a polydispersity index (PDI) of 0.286. Detailed investigations into crystallinity and Fourier transform infrared (FTIR) analysis did not reveal any indications of molecular interaction. Both the IMI‐CIL loaded NLCs and the hydrogel exhibited sustained in‐vitro drug release. Moreover, the hydrogel, enriched with permeation enhancers, demonstrated a remarkable 15.77‐fold increase in drug permeation. Furthermore, the IMI‐CIL loaded NLCs exhibited significantly elevated antibacterial activity when juxtaposed with IMI‐CIL solution, which demonstrated minimal activity against non‐resistant bacterial species and lacked activity against resistant isolates. In summary, the IMI‐CIL loaded NLCs hydrogel formulation assumes a pivotal role in bestowing sustained drug release and augmenting the antibacterial efficacy of carbapenem antibiotics. This holds promise as a potential solution to combat drug‐resistant bacterial infections.

Magnetic silk fibroin nanospheres loaded with amphiphilic polypeptides and antibiotics for biofilm eradication.

The eradication of established biofilms is a highly challenging task, due to the protective barrier effect of extracellular polymeric substances (EPS) and the presence of persister cells. Both increased drug permeability and elimination of persister cells are essential for the eradication of biofilms. Here, magnetic silk fibroin nanospheres loaded with antibiotics and host defense peptide (HDP) mimics (MPSN/S@P) were developed to demonstrate a new strategy for biofilm eradication. As an HDP mimic, an amphiphilic polypeptide containing 90% L-lysine and 10% L-valine (Lys90Val10) was selected for loading onto magnetic silk fibroin nanospheres via electrostatic interactions. Lys90Val10 exhibited excellent antibacterial activities against both planktonic and persister cells of Staphylococcus aureus (S. aureus). As a representative of the hydrophobic drug, spiramycin (SPM) was conveniently embedded into the β-sheet domain during the self-assembly process of silk fibroin. The sustained release of SPM during biofilm eradication enhanced the antibacterial efficacy of MPSN/S@P. The antibacterial test demonstrated that the extract from the MPSN/S@P suspension can kill both planktonic and persister cells of S. aureus, as well as inhibiting biofilm formation. Importantly, with the assistance of magnetic guidance and photothermal effects derived from Fe3O4 nanoparticles (Fe3O4 NPs), over 92% of bacteria in the biofilm were killed by MPSN/S@P, indicating the successful eradication of mature biofilms. The simple preparation method, integration of photothermal and magnetic responsiveness, and persister cell killing functions of MPSN/S@P provide an accessible strategy and illustrative paradigm for efficient biofilm eradication.

Advancements in Skin-Mediated Drug Delivery: Mechanisms, Techniques, and Applications.

Skin-mediated drug delivery methods currently are receiving significant attention as a promising approach for the enhanced delivery of drugs through the skin. Skin-mediated drug delivery offers the potential to overcome the limitations of traditional drug delivery methods, including oral administration and intravenous injection. The challenges associated with drug permeation through layers of skin, which act as a major barrier, are explored, and strategies to overcome these limitations are discussed in detail. This review categorizes skin-mediated drug delivery methods based on the means of increasing drug permeation, and it provides a comprehensive overview of the mechanisms and techniques associated with these methods. In addition, recent advancements in the application of skin-mediated drug delivery are presented. The review also outlines the limitations of ongoing research and suggests future perspectives of studies regarding the skin-mediated delivery of drugs.

The progress of fabrication designs of polymeric microneedles and related biomedical applications

AbstractMicroneedles (MNs) have been broadly used for transdermal delivery of a variety of drugs, ranging from small chemicals to biological macromolecules, due to the properties of increased drug permeability, minimal invasiveness and improved patient compliance. Despite these MNs can be made of different materials, such as metal, silicon, and glass, polymers have attracted the most attention as a microneedle (MN) matrix because of their excellent biocompatibility and biodegradability, which eliminates the requirement of MN removal after drug release. To satisfy different needs of transdermal drug delivery, polymeric MNs have been fabricated with several special designs. In this review, we summarize the advancement of the fabrication designs of polymeric MNs, including integrated MNs, two‐segment MNs, core‐shell or multi‐layered MNs, and arrowhead MNs. The related biomedical applications of MNs with these different specific designs are also discussed. Finally, we provide our perspectives on the future development of polymeric MNs.

Nanotechnology-based fungal detection and treatment: current status and future perspective.

Fungal infections impose a significant impact on global health and encompass major expenditures in medical treatments. Human mycoses, a fungal co-infection associated with SARS-CoV-2, is caused by opportunistic fungal pathogens and is often overlooked or misdiagnosed. Recently, there is increasing threat about spread of antimicrobial resistance in fungus, mostly in hospitals and other healthcare facilities. The diagnosis and treatment of fungal infections are associated with several issues, including tedious and non-selective detection methods, the growth of drug-resistant bacteria, severe side effects, and ineffective drug delivery. Thus, a rapid and sensitive diagnostic method and a high-efficacy and low-toxicity therapeutic approach are needed. Nanomedicine has emerged as a viable option for overcoming these limitations. Due to the unique physicochemical and optical properties of nanomaterials and newer biosensing techniques, nanodiagnostics play an important role in the accurate and prompt differentiation and detection of fungal diseases. Additionally, nano-based drug delivery techniques can increase drug permeability, reduce adverse effects, and extend systemic circulation time and drug half-life. This review paper is aimed at highlighting recent, promising, and unique trends in nanotechnology to design and develop diagnostics and treatment methods for fungal diseases.

Research trends and hot spots in global nanotechnology applications in liver cancer: a bibliometric and visual analysis (2000-2022).

Liver cancer (LC) is one of the most common malignancies. Currently, nanotechnology has made great progress in LC research, and many studies on LC nanotechnology have been published. This study aims to discuss the current status, hot spots, and research trends in this field through bibliometric analysis. The Web of Science Core Collection (WoSCC) database was searched for papers related to hepatocellular carcinoma (HCC) included from January 2000 to November 2022, and its research hotspots and trends were visualized and analyzed with the help of VOSviewer. In addition, a search was conducted to find LC papers related to nanotechnology. Then we used the visual analysis software VOSviewer and CiteSpace to evaluate the contributions of countries/regions, authors, and journals related to the topic and analyze keywords to understand the research priorities and hot spots in the field as well as the development direction. There are 1908 papers in the highly cited literature on LC, and its research hotspots are pathogenesis, risk factors, and survival rate. The literature on the application of nanotechnology in LC had 921 papers. Among them, China (n=560, 60.8%) and the United States (n=170, 18.5%) were the countries with the highest number of published papers. Wang Yan (n=11) and Llovet JM (n=131) were the first authors and co-cited authors, respectively. The International Journal of Nanomedicine was the most prolific academic journal (n=41). In addition to "hepatocellular carcinoma" and "nanoparticles", the most frequent keyword was "drug delivery". In recent years, "metastasis" and "diagnosis" appeared in the keyword bursts. This indicates that the application of nanoparticles in the early diagnosis and drug delivery of LC (including liver metastasis) has a good prospect. Nanotechnology has received more and more attention in the medical field in recent years. As nanoparticles are easily localized in organelles and cells, they can increase drug permeability in tumor tissues, improve drug delivery efficiency and reduce drug toxicity. Our research results were the first scientific evaluation of the application of nanotechnology in LC, providing scholars with research hotspots and development trends.

Analyzing the modulations induced in the mixed micellar behavior of 1-alkyl-3-butylimidazolium based surface-active ionic liquids with an antibiotic drug in aqueous media

Abstract The study aims to scrutinize the mixed micellization and interfacial behavior of two 1-alkyl-3-butylimidazolium based surface-active ionic liquids (SAILs) i.e., 1-decyl-3-butylimidazolium bromide [C10bim][Br] and 1-tetradecyl-3-butylimidazolium bromide [C14bim][Br] under the influence of streptomycin sulphate (SS) drug in 5 mM concentration in aqueous media. Imidazolium-based SAILs have unique physicochemical properties and greater surface activity than conventional surfactants, which allows them to increase drug permeability, making them better drug carriers than currently available formulations. To fully utilize [C14bim][Br] and [C10bim][Br] in drug delivery applications, deep insight into the interactions occurring in the mixed micellar [C10bim][Br]/[C14bim][Br] systems in the drug’s presence are necessary to be examined. Thus, the study is conducted using conductivity and surface tension measurement techniques to fully exploit the self-assembly, micellization behavior and interactions occurring in the pure and mixed micellar system of [C10bim][Br]/[C14bim][Br] in water and 5 mM of SS solution in aqueous media. For this, various thermodynamic, surface-active and mixed micellar parameters of micellization have been calculated and analyzed with respect to change in mole fraction, temperature and addition of SS in solution.

Anomalous Properties of Cyclodextrins and Their Complexes in Aqueous Solutions

Cyclodextrins (CDs) are cyclic oligosaccharides that emerged as industrial excipients in the early 1970s and are currently found in at least 130 marketed pharmaceutical products, in addition to numerous other consumer products. Although CDs have been the subject of close to 100,000 publications since their discovery, and although their structure and properties appear to be trivial, CDs are constantly surprising investigators by their unique physicochemical properties. In aqueous solutions, CDs are solubilizing complexing agents of poorly soluble drugs while they can also act as organic cosolvents like ethanol. CDs and their complexes self-assemble in aqueous solutions to form both nano- and microparticles. The nanoparticles have diameters that are well below the wavelength of visible light; thus, the solutions appear to be clear. However, the nanoparticles can result in erroneous conclusions and misinterpretations of experimental results. CDs can act as penetration enhancers, increasing drug permeation through lipophilic membranes, but they do so without affecting the membrane barrier. This review is an account of some of the unexpected results the authors have encountered during their studies of CDs as pharmaceutical excipients.

Atorvastatin Potentially Reduces Mycobacterial Severity through Its Action on Lipoarabinomannan and Drug Permeability in Granulomas.

The majority of preclinical research has shown that Mycobacterium tuberculosis can modify host lipids in various ways. To boost its intramacrophage survival, M. tuberculosis causes host lipids to build up, resulting in the development of lipid-laden foam cells. M. tuberculosis binds to and enters the macrophage via the cell membrane cholesterol. Aggregation of cholesterol in the cell wall of M. tuberculosis and an increase in vascularity at the granuloma site reduce the permeability of rifampicin and isoniazid concentrations. However, very few studies have assessed the effect of statins on drug penetration. Here, we used atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, to observe its effect on the bacterial burden by increasing the drug concentration at the infection site. We looked into how atorvastatin could be used in conjunction with first-line drugs to promote drug permeation. In this study, we detected an accumulation of drugs at the peripheral sites of the lungs and impaired drug distribution to the diseased sites. The efficacy of antituberculosis drugs, with atorvastatin as an adjunct, on the viability of M. tuberculosis cells was demonstrated. A nontoxic statin dosage established phenotypic and normal granuloma vasculature and showed an additive effect with rifampicin and isoniazid. Our data show that statins help to reduce the tuberculosis bacterial burden. Our findings reveal that the bacterial load is connected with impaired drug permeability resulting from lipid accumulation in the bacterial cell wall. Statin therapy combined with antituberculosis medications have the potential to improve treatment in tuberculosis patients. IMPORTANCE Mycobacterium tuberculosis binds to and enters the macrophage via the cell membrane cholesterol. M. tuberculosis limits phagosomal maturation and activation without engaging in phagocytosis. Aggregation of cholesterol in the cell wall of M. tuberculosis and an increase in the vascularity at the granuloma site reduce the permeability of rifampicin and isoniazid concentrations. However, very few studies have assessed the effect of statins on drug penetration, which can be increased through a reduction in cholesterol and vascularity. Herein, we used atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, to observe its effect on bacterial burden through increasing the drug concentration at the infection site. Our main research goal is to diminish mycobacterial dissemination and attenuate bacterial growth by increasing drug permeability.

NANO-DELIVERY SYSTEMS FOR ENHANCING ORAL BIOAVAILABILITY OF DRUGS

The two main issues impacting oral delivery are drug solubility and permeability. The FDA adopted the Biopharmaceutics Classification System (BCS) in 2000. The BCS categorizes drugs into four classes based on their solubility and permeability. For permeability improvement and bioavailability, many experimental systems are utilized. Numerous nanocarrier technologies have recently been utilized to increase drug permeability by employing nanocarrier systems such as lipid vesicles, polymeric and lipid nanoparticles, polymeric micelles, and submicron lipid emulsions. This review proposes innovative nano-delivery systems for permeability augmentation. It focuses on some illustrations of drugs with various nanosystems, how these systems were developed, and how they successfully boost intestinal drug permeability and bioavailability.

Chemical Attachment of 5-Nitrosalicylaldimine Motif to Silatrane Resulting in an Organic-Inorganic Structure with High Medicinal Significance.

Two chemical motifs of interest for medicinal chemistry, silatrane as 1-(3-aminopropyl) silatrane (SIL M), and nitro group attached in position 5 to salicylaldehyde, are coupled in a new structure, 1-(3-{[(2-hydroxy-5-nitrophenyl)methylidene]amino}propyl)silatrane (SIL-BS), through an azomethine moiety, also known as a versatile pharmacophore. The high purity isolated compound was structurally characterized by an elemental, spectral, and single crystal X-ray diffraction analysis. Given the structural premises for being a biologically active compound, different specific techniques and protocols have been used to evaluate their in vitro hydrolytic stability in simulated physiological conditions, the cytotoxicity on two cancer cell lines (HepG2 and MCF7), and protein binding ability-with a major role in drug ADME (Absorption, Distribution, Metabolism and Excretion), in parallel with those of the SIL M. While the latter had a good biocompatibility, the nitro-silatrane derivative, SIL-BS, exhibited a higher cytotoxic activity on HepG2 and MCF7 cell lines, performance assigned, among others, to the known capacity of the nitro group to promote a specific cytotoxicity by a "activation by reduction" mechanism. Both compounds exhibited increased bio- and muco-adhesiveness, which can favor an optimized therapeutic effect by increased drug permeation and residence time in tumor location. Additional benefits of these compounds have been demonstrated by their antimicrobial activity on several fungi and bacteria species. Molecular docking computations on Human Serum Albumin (HSA) and MPRO COVID-19 protease demonstrated their potential in the development of new drugs for combined therapy.

Ginger Extract-Loaded Sesame Oil-Based Niosomal Emulgel: Quality by Design to Ameliorate Anti-Inflammatory Activity.

Ginger, a natural plant belonging to the Zingeberaceae family, has been reported to have reasonable anti-inflammatory effects. The current study aimed to examine ginger extract transdermal delivery by generating niosomal vesicles as a promising nano-carrier incorporated into emulgel prepared with sesame oil. Particle size, viscosity, in vitro release, and ex vivo drug penetration experiments were performed on the produced formulations (ginger extract loaded gel, ginger extract loaded emulgel, ginger extract niosomal gel, and ginger extract niosomal emulgel). Carrageenan-induced edema in rat hind paw was employed to estimate the in vivo anti-inflammatory activity. The generated ginger extract formulations showed good viscosity and particle size. The in vitro release of ginger extract from niosomal formulation surpassed other formulations. In addition, the niosomal emulgel formulation showed improved transdermal flux and increased drug permeability through rabbit skin compared to other preparations. Most importantly, carrageenan-induced rat hind paw edema test confirmed the potential anti-inflammatory efficacy of ginger extract niosomal emulgel, compared to other formulations, as manifested by a significant decrease in paw edema with a superior edema inhibition potency. Overall, our findings suggest that incorporating a niosomal formulation within sesame oil-based emulgel might represent a plausible strategy for effective transdermal delivery of anti-inflammatory drugs like ginger extract.