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Nanotechnology, a rapidly evolving science, has generated game-changing breakthroughs in the industrial, medical, and consumer industries. Engineered nano particles (NP) are extremely attractive in a range of applications due to their unique physio chemical and electrical characteristics. Changes in Np's structural and physio chemical properties can alter their biologically active compounds, along with the generation of free radicals (ROS), one of the most widely documented Nano particle-related toxins. Cellular parameters such as surface of the particle, size, contents of composition, and metal content produce oxidative stress, whereas cellular responses such as mitochondrial functions, Nano materials cell contact, and immune cell activation cause ROS-mediated destruction. It's crucial to understand how NP influences the ROS response although the oxidative stress is a key predictor of Nano particle induced damage. It may be possible to develop a comprehensive toxicity screen that uses oxidative stress as a prediction model for nano particle damage, as well as a better understanding of the multiple signalling cascades activated by nano materials ROS.

he Essential oils considered as promising veridical activity against various pathogenic viruses. Byanalyses we found out that essential oil constituent having any counter effect or interact with specific proteins present in COVID-19. The method to determine give in literature view by using databases resources such as, Semantic scholar, Google scholar, Science direct and PubMed. Result: In literature survey it is found out thataromatic plants containing essential oils having veridical activity against various viruses which include Herpes virus-2. Enterovirus 71, HIV, Adeno virus. From literature reviews its reveal that aromatic plant and essential oil having high antiviral activity for many viruses. It is found that some essential oils having some isolated compound which have inhibitory effect on COVID 19. According to analysis done by, its found out that 171 constituent of essential oil influencing SARS-COV-2 proteins and found potential inhibitor of viruses.

Chlorhexidine is a common skin antisepsis agent that is also found in toothpaste and mouthwash.When mixed with alcohol, it is a particularly efficient antibacterial. Because it forms a strong bond with aminoacid subunits in the peripheral skin and mucosal layers. Its antibacterial properties remain for a long time,enabling it to be an efficacious antiseptic agent. Chlorhexidine is applied on various medical devices which provide protection against various internal infections caused by catheter. Chlorhexidine-related contact dermatitis is uncommon among healthcare employees.in individuals where the incidence of allergic reactionsis very common, the rate of skin allergic reactions caused by chlorhexidine ranges from 3.5 to 6.5 percent.Chlorhexidine induced allergic reactions are frequently misdiagnosed, leading to under reporting.

Women have faced many challenges such as higher risk of breast cancer due to lack of awareness.The formation of hard mass or lump is a common sign. There are 4 stages of the breast cancer, and it is divided into two types, invasive and non-invasive. The common type is invasive ductal carcinoma which spread easily and also occur in men. The stage 3 cancer is known to be Inflammatory breast cancer and it can appear as metastatic cancer. Some risk factors can be controlled like breastfeeding can reduce chances of cancer. Different alternate options are selected for the treatment like full removal of breast or lump by the mastectomy or lumpectomy respectively. To destroy remaining cancerous cells, radiations are given, and chemotherapy reduces the size of tumor cell. In advance methods, gene therapy or immune system modulation is done to get rid of cancer.

This study aims to formulate mucoadhesive vancomycin loaded thiolated chitosan (TCS) nanoparticles. These nanoparticles are mucoadhesive and enhance the retention of the drug at the ocular site. For this purpose, TCS loaded vancomycin nanoparticles were prepared by the ion-gelation method and were characterized for their size, shape, polydispersity index, mucoadhesion, cellular uptake and anti-inflammatory activity. The average size of the synthesized nanoparticles was found to be 288 nm with positive zeta potential. Moreover, 85% vancomycin was successfully encapsulated in TCS nanoparticles by using this method. A 2-fold increase in mucoadhesion was found as compared to non-thiolated vancomycin formulation (p < 0.05). Zone of inhibition of vancomycin loaded TCS was also significantly improved compared to non-thiolated chitosan nanoparticles and vancomycin alone. In-vivo anti-inflammatory evaluation via histopathology resulted in ocular healing. Based on the results, it is inferred that TCS nanoparticles are a promising drug delivery carrier system for ocular delivery of vancomycin.

COVID-19 has posed a great threat to mankind, there is a dire need to introduce a vaccine to combat this global pandemic. Several vaccines are underway to complete their phase 3 clinical trials. This article highlights events surrounding the ongoing clinical trials of vaccines effective against COVID-19, and different procedures and formalities the vaccine will have to endure to get EUA. Clinical trials are discussed stepwise along with the clinical endpoint desired at the end of these trials. In line with antimicrobial resistance, vaccine resistance has also emerged in this era and needs focused consideration, and the probability of development of resistance in these vaccines is discussed. This article specifically covers the latest research reporting clinical efficacy, safety profile, and adverse events following the administration of doses to patients and concerns regarding the rushed approval of vaccines. Four vaccines have been discussed in detail; BNT162b2, mRNA-1273, Sputnik V, ChAdOx1.

Different nanocarrier systems owing to their nano size, increased surface area and unique electrical and magnetic properties are employed for biomedical applications. Among the various nanocarrier systems, hollow nanocapsules are one of the most interesting carrier systems for thier use in bioimaging and biomedical applications. The unique properties of hollow nanocapsules make them suitable for use in bioimaging. In this article hollow nanocpsules have been classified into four classes based on thier composition: (i) liposomes, (ii) polmersomes and other polymeric hollow nanocapsules, (iii) metallic hollow nanocapsules and (iv) others. The formation and design of these hollow nanocapsules and their diagnostic and therapeutic applications using different agents/imaging probes and imaging modalities is discussed briefly. Hollow nanocapsules have revolutionized the field of biomedical imaging.

Mannose receptors (MR) are highly over-expressed on macrophages in the inflammatory bowel disease (IBD) and can be targeted by developing mannose-anchored nano-carrier system. In this study, mannosylated chitosan (MC) polymer was synthesized because of its high affinity for mannose receptors. Afterward, MC nanoparticles (NPs) were fabricated encapsulating dexamethasone to target macrophages for attenuation of inflammation at initial stages. Further, NPs were coated with a pH-sensitive polymer to control the premature drug release in the stomach. NPs were optimized using a surface response quadratic model to study the impact of various process parameters. Optimized NPs were then characterized for size, morphology, zeta potential, surface chemistry, biocompatibility, and uptake by macrophages. The average particle size was found to be 380 ± 19.8 nm with an encapsulation efficiency of 78.1 ± 1.17%. pH-dependent drug release profile was obtained with an average release of 73.9 ± 5.24% over 72 h in simulated intestinal fluid (pH 7.4). Moreover, the NPs uptake by the macrophages supported the viability of macrophages with the NPs and did not show any adverse effects. Moreover, this study was supported by the uptake of NPs inside macrophages. Altogether, the data supported that MC NPs could serve as a potential anti-inflammatory therapeutic approach to target macrophages in IBD.

The present study aimed on the site specific delivery and enhanced in-vivo efficacy of antimonial drugs against the visceral leishmaniasis via macrophage targeted mannose anchored thiomer based nanoparticles. Mannose anchored thiolated nanoformulation [M-(CS-g-PEI)-TGA] was developed and evaluated in terms particle size, zeta-potential and entrapment efficacy. The TEM and EDX analysis was carried out to evaluate the morphology and successful entrapment of antimonial drug. Mucodhesion, permeation enhancement, oral pharmacokinetics, and in-vivo anti-leishmanial activity were carried out. The M-(CS-g-PEI)-TGA were found to be spherical having particle size of 287 ± 20 nm. Ex-vivo permeation indicated a 7.39-fold enhanced permeation of Meglumine Antimoniate with M-(CS-g-PEI)-TGA across Caco-2 cells compared to the Glucantime. Evaluation of in-vitro reduction in the parasitic burden via flow cytometric analysis indicated a 5.7-fold lower IC50 for M-(CS-g-PEI)-TGA compared to Glucantime. A 6.1-fold improvement in the oral bioavailability and 5.2-fold reduced parasitic burden in the L. donovani infected BALB/c mice model was observed with M-(CS-g-PEI)-TGA compared to Glucantime. The results encouraged the concept of M-(CS-g-PEI)-TGA nanoformulations as a promising strategy for oral therapy against visceral leishmaniasis.

The present study was intended to develop a papain grafted S-protected hyaluronic acid-lithocholic acid co-block (PAP-HA-ss-LCA) polymeric excipient as an amphiphilic muco permeating stabilizer for targeting breast cancer epithelial cells overexpressed with CD44 receptors. The mucopermeating, stabilizing and targeting capability of the PAP-HA-ss-LCA polymeric excipient was investigated by manufacturing tamoxifen (TMX) loaded self-nanoemulsifying drug delivery system (SNEDDS). TMX loaded PAP-HA-ss-LCA incorporated SNEDDS (TMX-PAP-HA-ss-LCA SNEDDS) were characterized for their surface chemistry, drug release, permeation enhancement, biocompatibility and antitumor activity. FTIR spectroscopic analysis showed successful synthesis of PAP-HA-ss-LCA polymer. X-ray diffraction (XRD) showed the amorphous form of TMX inside SNEDDS. The observed hydrodynamic diameter of TMX-PAP-HA-ss-LCA SNEDDS was 367.5 nm. Furthermore, Hyaluronic Acid-based Mucoadhesive Self Nanoemulsifying Drug Delivery System (SNEDDS) of TMX showed homogeneity in synthesis with low polydispersity and negative zeta potential due to stabilization with PAP-HA-ss-LCA polymer. The distinct spherical shape of the nanodroplets was evident by transmission electron microscopy (TEM). In vitro release kinetics indicated approximately >80% release within 48 h under sink conditions. Ex-vivo permeation study displayed 7.11-folds higher permeation of TMX by TMX-PAP-HA-ss-LCA in contrast to pure TMX. The biocompatibility study proved that SNEDDS formulation was safe and compatible against macrophages. In vitro cytotoxicity studies demonstrated that TMX-PAP-HA-ss-LCA SNEDDS could efficiently kill MCF-7 breast cancer cells as compared to the native TMX drug. Systemic toxicity studies proved the non-toxic nature of TMX-PAP-HA-ss-LCA in contrast to pure TMX. Based on these evidences, TMX-PAP-HA-ss-LCA SNEDDS formulation seems to be promising mucopermeating, augmented intracellular uptake with strong targeting potential for anti-proliferative activity.

INTRODUCTION: Infectious diseases associated with intracellular bacteria such as Staphylococcus aureus, Salmonella typhimurium and Mycobacterium tuberculosis are important public health concern. Emergence of multi and extensively drug-resistant bacterial strains have made it even more obstinate to offset such infections. Bacteria residing within intracellular compartments provide additional barriers to effective treatment. METHOD: Information provided in this review has been collected by accessing various electronic databases including Google scholar, Web of science, Scopus, and Nature index. Search was performed using keywords nanoparticles, intracellular targeting, multidrug resistance, Staphylococcus aureus; Salmonella typhimurium; Mycobacterium tuberculosis. Information gathered was categorized into three major sections as ‘Intracellular targeting of Staphylococcus aureus, Intracellular targeting of Salmonella typhimurium and Intracellular targeting of Mycobacterium tuberculosis’ using variety of nanocarrier systems. RESULTS: Conventional management for infectious diseases typically comprises of long-term treatment with a combination of antibiotics, which may lead to side effects and decreased patient compliance. A wide range of multi-functionalized nanocarrier systems have been studied for delivery of drugs within cellular compartments where bacteria including Staphylococcus aureus, Salmonella typhimurium and Mycobacterium tuberculosis reside. Such carrier systems along with targeted delivery have been utilized for sustained and controlled delivery of drugs. These strategies have been found useful in overcoming the drawbacks of conventional treatments including multi-drug resistance. CONCLUSION: Development of multi-functional nanocargoes encapsulating antibiotics that are proficient in targeting and releasing drug into infected reservoirs seems to be a promising strategy to circumvent the challenge of multidrug resistance. [Figure: see text]

Increasing drift in antimicrobial therapy failure against Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), and the advent of extended resistant strains strongly demand discovery of mechanisms underlying development of drug resistance. The emergence of resistance against anti-TB drugs has reached an alarming level in various parts of the world, providing an active platform for the design of new targeted drug delivery. Reactive oxygen species (ROS) have an important role in controlling TB pathogenesis. At macrophage activation, ROS that are produced inside macrophages directly kill resident bacteria. These ROS possess a dual character because they can kill macrophages along with the resident bacteria. Targeting these ROS can play a remarkable part in overcoming resistance of conventional drugs. Nanoparticles (NPs) have evolved as a potential drug carrier for targeted delivery and elimination of various resistance mechanisms against antimicrobials. Receptor-mediated targeting of macrophages via different NPs may be a promising strategy for combating drug resistance and enhancing efficacy of old-fashioned antimycobacterial agents.

Carbon nanotubes (CNTs) belong to the fullerene family, also known as graphene. These graphenes are similar to the graphite sheets and when these are turn up in the cylindrical form they are known as carbon nanotubes. Currently, the most common methods used for CNTs preparation are: Electric-arc-discharge methods, Chemical-vapor-deposition method and Laserablation method. In order to cross the cell membrane, functionalization of the pristine CNTs is performed. Because of the sp2 hybridization and closely packed hexagons in their structure, functionalization of the pristine CNTs can be done easily with either therapeutic agent or the imaging agent. They have wide applications in the field of bio-imaging because of their intrinsic optical, mechanical and electrical properties. They can be used as efficient contrast agents and the biosensors as well as efficient carriers for the delivery of therapeutic or imaging agents.

There are many publications that deal with the administration of test substances to animals and the removal of blood samples for different objectives. The parenteral route of drug administration includes further different routes, i.e., drug administration through muscles (IM route) through veins (IV route) and through subcutaneous route. We can manage to check the outcomes of test substances within minutes when we go for the IV route as in this route; the drug directly goes to the systemic circulation. Different experimental animals are utilized to check the possible outcomes of test substances that include Rabbit, mice, and rat. Various factors like dose strength, dose frequency and the meaning by which drug can be administered to an animal can be examined. The emphasis on drug safety should be the main priority while injecting drug substances. Animal ethics guidelines should be followed in this regard. AEG basically provides us with safety guidelines that should be followed for safe handling.

P-glycoprotein (P-gP) efflux-mediated multidrug resistance is a fundamental aspect of chemotherapeutic failure in oncology. The current study aims to deliver paclitaxel (PTX) specifically at the target site with improved in vivo efficacy of poorly permeable PTX against solid tumors. Multifunctional polymeric micelles as targeted delivery have been devised for loading and release of PTX. Mucoadhesion, permeation enhancement, oral pharmacokinetics, biodistribution, and toxicological studies were carried out to fully elucidate the therapeutic outcomes of the polymeric micelles. Ex vivo permeation studies indicated a 7.89-fold enhancement in the permeation of PTX with mucopermeating papain functionalized thiolated redox micelles (PT-R-Ms) compared to the pure PTX. Moreover, PT-R-Ms exhibited a higher percentage of apoptotic cells (42.9 & PLUSMN; 0.07%) compared to pure PTX. Biodistribution studies revealed that fluorotagged PT-RMs accumulated in excised tumors and organs. The higher fluorescence intensity indicated the mucopermeation of micelles across the intestine. The orally administered PT-R-Ms efficiently overcome intestinal barriers and inhibit the P-gP efflux pump, resulting in increased bioavailability of PTX (up to 8-fold) in comparison to pure PTX. The enhanced anti-tumor efficacy and reduced toxic effects are key aspects of efficient cancer therapy. This study demonstrates that the use of mucopermeating PT-R-Ms is an encouraging approach to overwhelm the permeation barrier in cancer treatment., Comunidad de Madrid

Site-specific delivery of antibiotics has always been a high-priority area in pharmaceutical research. Conventionally used antibiotics suffer several limitations, such as low accumulation and penetration in diseased cells/tissues, limited bioavailability of drugs, drug resistance, and off-target toxicity. To overcome these limitations, several strategies have been exploited for delivering antibiotics to the site of infection, such as the use of stimuli-responsive antibiotic delivery systems, which can release antibiotics in a controlled and timely fashion. These stimuli can either be exogenous (light, magnetism, ultrasound, and electrical) or endogenous (pH, redox reactions, and enzymatic). In this review, we present a summary of recent developments in the field of stimuli-based targeted drug delivery systems for the site-specific release of antibiotics.

We have demonstrated the enhanced in vivo oral efficacy and enhanced hepatoprotective effects of preactivated thiolated chitosan (Cht) nanoparticles (NPs) for tuberculosis. The mannose anchored preactivated thiolated chitosan nanoparticles (MPTCht-NPs) were prepared and characterized in terms of their particle size, in vitro entrapment efficiency (EE%) and zeta potential (mV). NPs were also evaluated in terms of mucoadhesion, % hemolysis, permeation enhancement, in vivo pharmacokinetics, toxicity and immunomodulation. NPs exhibited an average particle size of 307 nm with 19 folds enhanced permeation in comparison to conventional Rifampicin (Rif) formulation across everted rat intestine. The evaluation of in vivo pharmacokinetic parameters indicated 16 folds improvement in oral bioavailability in comparison to Rif alone following oral administration in rabbits. There was significant difference in the levels of serum transaminases, oxidative stress markers, and expression levels of anti-apoptotic (Bcl-2) and pro-apoptotic (Bax) genes between Rif treated and NPs treated groups. The serum transaminases levels were normal with MPTCht-NPs treated groups as compared to Rif treated groups while the levels of glutathione were markedly increased in MPTCht-NPs treated group. Furthermore, the levels of Bax were enhanced with the MPTCht-NPs treatment. In summary, these findings revealed that the designed NPs may act as promising therapeutic strategy against tuberculosis in a dose-dependent manner while providing the immunomodulation and hepatoprotective effect.

This study aimed to design a hyaluronic acid-based targeted, mucoadhesive and mucopenetrating drug delivery system encapsulating clarithromycin that would improve the drug residence time at H. pylori infection site. Clarithromycin-loaded thiolated hyaluronic acid-co-oleic acid (CLR-thHA-co-OA), clarithromycin-loaded ureido-conjugated thiolated hyaluronic acid-co-oleic acid (CLR-Ur-thHA-co-OA), and clarithromycin-loaded papain-modified ureido-conjugated thiolated hyaluronic acid-co- oleic acid (CLR-PAP-Ur-thHA-co-OA) nanomicelles were prepared by an ultra-sonication method. FTIR data confirmed the successful grafting of the different ligands to polymer backbone. XRD analysis revealed the amorphous nature of the polymer conjugate and drug inside nanomicelles. The critical micelle concentration of PAP-Ur-thHA-co-OA nanomicelles was found to be 15.85 µg/ml. Also, the sizes of nanomicelles were in the range of 210–258 nm. TEM analysis of CLR-PAP-Ur-thHA-co-OA nanomicelles confirmed their small size and spherical shape. Zeta potential and entrapment efficiency of CLR-PAP-Ur-thHA-co-OA nanomicelles were –24 mV and 80 ± 7.2% respectively. A sustained drug release pattern was observed for all types of prepared nanomicelles, whereas CLR-PAP-Ur-thHA-co-OA ones also displayed improved stability at acidic pH. Due to the presence of thiol groups in the polymer backbone, thiolated nanomicelles displayed important mucoadhesive properties. In this regard, FDA loaded PAP-Ur-thHA-co-OA nanomicelles showed the deepest penetration distance into the mucus by cleavage of mucoglycoproteins when compared to papain-unmodified nanomicelles. Fluorescent images of gastric tissues revealed the greater gastric retention time of nanomicelles compared to the free drug. As consequence, an enhanced in vitro efficacy against H. pylori was observed by nanomicelles. The in vivo clearance study showed an improved eradication of H. pylori by CLR-PAP-Ur-thHA-co-OA nanomicelles in comparison to other nanoformulations. Thus, the newly synthesized CLR-PAP-Ur-thHA-co-OA nanomicelles have the potential to be used as an efficient nanocarrier for H. pylori infection treatment due to their enhanced mucopenetration and mucoadhesion properties, as well as their improved stability and extended drug release P.T also thanks Agencia Estatal de Investigación (AEI) by project PID2019-109517RB-I00. ERDF funds are also acknowledged SI

Aim: The present study evaluates the efficacy of paromomycin (PM)-loaded mannosylated thiomeric nanoparticles for the targeted delivery to pathological organs for the oral therapy of visceral leishmaniasis. Materials & methods: Mannosylated thiolated chitosan (MTC)-coated PM-loaded PLGA nanoparticles (MTC-PLGA-PM) were synthesized and evaluated for morphology, drug release, permeation enhancing and antileishmanial potential. Results: MTC-PLGA-PM were spherical in shape with a size of 391.24 ± 6.91 nm and an encapsulation efficiency of 67.16 ± 14%. Ex vivo permeation indicated 12.73-fold higher permeation of PM with MTC-PLGA-PM against the free PM. Flow cytometry indicated enhanced macrophage uptake and parasite killing in Leishmania donovani infected macrophage model. In vitro antileishmanial activity indicated 36-fold lower IC50 for MTC-PLGA-PM as compared with PM. The in vivo studies indicated 3.6-fold reduced parasitic burden in the L. donovani infected BALB/c mice model. Conclusion: The results encouraged the concept of MTC-PLGA-PM nanoparticles as promising strategy for visceral leishmaniasis.

The frequency of prostate cancer varies worldwide. Western people are more prone to this disease. Genetic changes and inflammation are the two most common causes of pathogenesis of prostate carcinoma. Genes taking part in progression of prostate cancer including GSTP1, RNASEL, PTEN/MXi1, AR gene pathway including PI3/AKT also leads to prostate cancer. Besides genes, inflammation, elevated VEGF, diet, environmental changes, and alteration in the androgen receptor are predisposing aspect for prostate cancer. The development of science and technology had led to astonishing modifications in treatment strategies. It is a slow-growing tumor and confined to the prostate only. The key objective of treatment is to reduce the level of testosterone. Different approaches are employed for treatment including hormonal therapy, cryosurgery, anti-tumor medication, and receptor-based treatment in which androgen receptors are major targets. The latest treatment of prostate cancer includes nanoparticle targeted delivery of antiandrogens.

There are a very large number of drugs that enter in the clinical trial phase but only a fraction of them is able to get their place in market. For a drug to reach at a phase of clinical trial requires a huge effort of research and a very large investment. Translational medicine, a relatively new discipline, uses the novel techniques that not only lower the risk of investment failure, but also focuses on reducing the testing duration in different phases of clinical trials. Discussed in the article are advantages of translational medicines and various challenges faced by translational medicine as well the ways by which this discipline will face these challenges. This article also focuses on recent advances in therapeutic development for diabetes, bone disorders, neurosciences, and oncology and the failures of translational medicine due to high external risk factors.

The main objective of this study was to investigate polyethylene imine (PEI) based stereocomplexed nanomiceles for intracellular delivery of rifampicin against Mycobacterium bovis (M. bovis) and their in vitro-in vivo evaluation. The formation of Rifampicin (Rif) loaded isotactic (PEI-g-PLLA and PEI-g-PDLA) and stereocomplexed nanomicelles (StM) of PEI conjugated poly l- and poly d-lactic acid via self-assembly was thoroughly explored. Synthesis of polymer graft was confirmed via FTIR and NMR. A 2-fold reduction in CMC of StM was observed along with decreased particle size in comparison to isotactic nanomicelles. In vitro, StM exhibited a higher encapsulation efficiency and 84 % of drug release in 48 h. at pH 5 with minimal initial burst release in comparison to isotactic nanomicelles. Minimum inhibitory concentration (MIC) of StM was found to be four folds lower in contrast to isotactic nanomicelles. Ex vivo studies exhibited a better uptake of StM and minimum cytotoxicity in murine alveolar macrophages. Following oral administration in mice, drug loaded StM exhibited highest distribution in macrophage rich organs, longer half-life, AUC, AUMC and MRT in comparison to isotactic nanomicelles indicating maximum bioavailability and efficacy of StM. In vivo antimycobacterial activity also demonstrated a higher reduction (2.38fold) in M. bovis CFU at reduced dosing frequency by drug loaded StM in comparison to control group. Thus, StM can be regarded as a simple, stable, efficient, and biocompatible carrier system for delivery of rifampicin to intracellular M. bovis with added advantage of reduced dosing frequency and improved patient compliance.

A novel quality by design-based high performance liquid chromatographic method was developed for levosulpiride. There was no specific method for levosulpiride in United States Pharmacopeia. So, for the first time Quality by Design approach was implemented by Box- Behnken Design. Method specifications include; buffer (low molarity): acetonitrile (50:50), column c18, pH 7 and flow rate 0.6 mL/min. Use of low molarity buffer increases the column life, 3.8 min fast retention time as compared with previously reported methods. A highly statistical significant model was obtained by employing Box- Behnken Design with p value < 0.05. Chromatographic conditions selected within the Method Operable Design Region (MODR). Limit of detection in buffer/acetonitrile was 0.036 μg/mL, and the limit of quantification was 0.11 μg/mL, however, limit of quantification in plasma was 18.57 ng/mL. The method was employed successfully for assessment of levosulpiride in various pharmaceutical formulations. Additionally, the developed method was used for pharmacokinetic studies of four different dosage forms of levosulpiride in human volunteers. The developed method is rapid, robust and sensitive and successfully employed for detection of levosulpiride in human plasma.

A facile, green synthesis of selenium doped zinc oxide nano-antibiotic (Se-ZnO-NAB) using the Curcuma longa extract is reported to combat the increased emergence of methicillin-resistant Staphylococcus aureus (MRSA). The developed Se-ZnO-NAB were characterized for their physicochemical parameters and extensively evaluated for their toxicological potential in an animal model. The prepared Se-ZnO-NABs were characterized via Fourier transformed infrared spectroscopy to get functional insight into their surface chemistry, scanning electron microscopy revealing the polyhedral morphology with a size range of 36 ± 16 nm, having -28.9 ± 6.42 mV zeta potential, and inductively coupled plasma optical emission spectrometry confirming the amount of Se and Zn to be 14.43 and 71.70 mg L-1 respectively. Moreover, the antibacterial activity against MRSA showed significantly low minimum inhibitory concentration at 6.2 μg mL-1 when compared against antibiotics. Also, total protein content and reactive oxygen species production in MRSA, under the stressed environment of Se-ZnO-NAB, significantly (p < 0.05) decreased compared to the negative control. Moreover, the results of acute oral toxicity in rats showed moderate variations in blood biochemistry and histopathology of vital organs. The teratogenicity and fetal evaluations also revealed some signs of toxicity along with changes in biochemical parameters. The overall outcomes suggest that Se-ZnO-NAB can be of significant importance for combating multi-drug resistance but must be used with extreme caution, particularly in pregnancy, as moderate toxicity was observed at a toxic dose of 2000 mg kg-1.

Fungal infections in immune-compromised patients are an important cause of mortality and morbidity. Amphotericin B (Amp B) is considered a powerful fungicidal drug but its clinical usage has certain limitations when administered intravenously due to its toxicity and poor solubility. In consideration of such challenges, in cutaneous leishmaniasis, the topical application of Amp B can be a safer option in many aspects. Thus, herein, biopolymer of polycaprolactone (PCL) nanoparticles (NPs) were developed with the loading of Amp B by nanoprecipitation for the treatment of topical leishmanial infections. Various parameters, such as concentration of PCL and surfactant Poloxamer 407, were varied in order to optimize the formation of nanoparticles for the loading of Amp B. The optimized formulation exhibited a mean hydrodynamic particle size of 183 nm with a spherical morphology and an encapsulation efficiency of 85%. The applications of various kinetic models reveal that drug release from nanoformulation follows Korsmeyer&ndash, Peppas kinetics and has a high diffusion exponent at a physiological pH of 7.4 as well a skin relevant pH = 5.5. The activity of the prepared nanoparticles was also demonstrated in Leishmania infected macrophages. The measured IC50 of the prepared nanoparticle formulation was observed to be significantly lower when compared to control free Amp B and AmBisome&reg, for both L. tropica KWH23 and L. donovani amastigotes in order to demonstrate maximum parasite inhibition. The prepared topical nanoformulations are capable of providing novel options for the treatment of leishmaniasis, which can be possible after in vivo assays as well as the establishment of safety profiles.

We report the synthesis, characterization and evaluation of lecithin-drug hybrid nanocarriers (NCs) with enhanced oral bioavailability and anti-parasitic potential for poorly water-soluble drugs. Amphotericin B (AmB), a poor water-soluble drug with poor membrane penetrating ability, was selected as a model drug to demonstrate the potential of the lecithin-drug hybrid NCs. Lec-AmB NCs were prepared by the self-assembly of lecithin into nanoparticles (NPs) at a critical micellar concentration of 4 mg ml−1 and into liposomes at a critical liposomal concentration of 53 mg ml−1 in aqueous systems. The Lec-AmB NPs (200–300 nm) were further coated with polyethylene glycol (MW 600) and Tween 20, whereas the liposomes (70–90 nm) were used as such for this study. The Lec-AmB NCs were evaluated for their ability to boost in vivo oral pharmacokinetic parameters in rabbits and in vitro anti-leishmanial activity against the promastigotes of Leishmania tropica. A reciprocal relationship was observed between the size and drug encapsulation efficiency of the NPs, but no such relationship was observed in the case of the liposomes. More importantly, the oral bioavailability and anti-leishmanial activity of Lec-AmB NPs was enhanced up to 21- and 6.3-fold, and 21- and 2-fold, respectively, in the case of the liposomes. The improvement in the bioavailability and anti-leishmanial activity is very significant compared to the deoxycholate complex of AmB (water soluble, injectable market product: Anfotericina FADA®), and this study, thus shows the promising potential of easy-to-prepare NCs with improved therapeutic efficiency using phosphocholine-based biocompatible surfactants.

Microneedle patch is a prominent strategy with minimal invasion and painless application to improve skin penetration of drug molecules. Herein, we report microneedle patch (MNP) as an alternative to the oral route for the systemic delivery of tacrolimus (TM), an immunosuppressant drug. Thiolated chitosan (TCS) based microneedle patch was fabricated and characterized in vitro and in vivo for its mechanical strength, skin penetration, drug release, and skin irritation. The MNP having 225 needles with 575 μm showed good mechanical properties in terms of tensile strength and percentage elongation. The skin penetration showed 84% penetration with no breakage. Histology of the mice skin after insertion showed the penetration of needles into the dermis. In vitro release and ex vivo permeation studies through Franz diffusion cell showed the sustained release (82.5%) of TM from the MNP with significantly higher (p

The formation of biofilm by Streptococcus mutans on the tooth surface is the primary cause of dental caries and periodontal diseases, and fluoride (F) has shown tremendous potential as a therapeutic moiety against these problems. Herein, we report an efficient multi-ingredient bioadhesive film-based delivery system for oral cavity to combat dental problems with an ease of administration. Thiolated chitosan-based bioadhesive film loaded with calcium fluoride nanoparticles (CaF2 NPs) and lignocaine as a continuous reservoir for prolonged delivery was successfully prepared and characterized. The polygonal CaF2 NPs with an average particle size less than 100 nm, PDI 0.253, and + 6.10 mV zeta potential were synthesized and loaded in film. The energy dispersive x-ray (EDX) spectroscopy confirmed the presence 33.13% F content in CaF2 NPs. The characterization of the three film trials for their mechanical strength, bioadhesion, drug release, and permeation enhancement suggested film B as better among the three trials and showed significant outcomes, indicating the potential application of the medicated bioadhesive film. In vitro dissolution studies revealed sustained release pattern of lignocaine and CaF2 NP following Krosmeyer-Peppas model over 8 h. Franz diffusion studies showed the prolonged contact time of film with mucosa that facilitated the transport of CaF2 NPs and lignocaine across the mucosa. Hence, the prepared bioadhesive film-based system showed good potential for better management of dental problems.

The study was aimed to develop amoxicillin (AM) loaded thiomer based mucopermeating and mucoadhesive nanocarrier system that allows it to reach the bacterium, hiding in deeper mucus layers and extends its availability at infection site. Amoxicillin loaded nanocargoes were prepared using unmodified polycarbophil (PCP), thiolated polycarbophil (PCP-Cys), and papain modified thiolated polycarbophil (PCP-Cys-PAP) by ionic gelation method and processed for in vitro and ex vivo and in vivo characterization. All the nanocargoes were in size range of 111–288 nm. Drug loaded papain modified thiolated polycarbophil (AM-PCP-Cys-PAP) based nanocargoes showed an entrapment efficiency of 78 ± 7.2%, a zeta potential of − 13.4 mV and spherical shape. Both AM-PCP-Cys and AM-PCP-Cys-PAP exhibited a sustained release of drug up to 48 h and AM-PCP-Cys-PAP nanocargoes showed significant stability in acidic pH as compared to pure drug. Rheological investigation demonstrated a twofold higher mucoadhesion for thiolated polycarbophil nanocargoes. Ex vivo muco-penetration studies demonstrated deepest permeation of papain modified nanocargoes into the mucus. Cytotoxicity analysis showed that nanocarrier formulations were non-toxic to Caco-2 cells and maintained cell viability after 48 h. In vitro growth inhibition assay for H. pylori exhibited better efficacy for AM-PCP-Cys-PAP nanocargoes in terms of improved stability along with complete eradication of bacteria over prolonged period of time. In vivo acute toxicity studies on vital organs of mice exhibited no significant change in cell morphology. In vivo clearance study showed that AM-PCP-Cys-PAP nanoformulation was successful in complete eradication of bacteria. Based on above findings, amoxicillin loaded papain modified thiolated polycarbophil nanocarrier system was able to completely eradicate H. pylori infection that was attributed to its enhanced mucopermeating and mucoadhesive nature. The functionalized nanocarriers showed an interesting future potential for infectious therapy.

The oral delivery of cancer chemotherapeutic drugs is challenging due to low bioavailability, gastrointestinal side effects, first-pass metabolism and P-glycoprotein efflux pumps. Thus, chemotherapeutic drugs, including Docetaxel, are administered via an intravenous route, which poses many disadvantages of its own. Recent advances in pharmaceutical research have focused on designing new and efficient drug delivery systems for site-specific targeting, thus leading to improved bioavailability and pharmacokinetics. A decent number of studies have been reported for the safe and effective oral delivery of Docetaxel. These nanocarriers, including liposomes, polymeric nanoparticles, metallic nanoparticles, hybrid nanoparticles, dendrimers and so on, have shown promising results in research papers and clinical trials. The present article comprehensively reviews the research efforts made so far in designing various advancements in the oral delivery of Docetaxel. Different strategies to improve oral bioavailability, prevent first-pass metabolism and inhibition of efflux pumping leading to improved pharmacokinetics and anticancer activity are discussed. The final portion of this review article presents key issues such as safety of nanomaterials, regulatory approval and future trends in nanomedicine research.