Knowledge, attitude, and perceptions of healthcare professionals towards complementary and alternative medicine: a cross-sectional survey from twin cities of Pakistan.

BACKGROUND: The growing popularity and use of complementary and alternative medicine (CAM) products among the general public worldwide has been well documented. This study aimed to investigate the knowledge, attitude, and perceptions (KAP) of Pakistani healthcare professionals (HCP) toward CAM and to document their views on integrating CAM education with the curriculum of undergraduate health science programs. METHOD: A cross-sectional study using simple random sampling was conducted for a duration of ten months among HCPs from Pakistan's twin cities: Islamabad and RawalpindiThe data were collected using a self-administered and validated (Cronbach's alpha: 0.71) questionnaire. This questionnaire consisted of five sections, namely; demographic, attitude, perception, integration and knowledge. RESULT: The response rate was 91.20% (500/456). The participants included 160 physicians, 155 nurses,and 141 pharmacists. The majority of the respondents were females, 67.50%, and unmarried (60.50%).The majority of HCPs participating in this study agreed that CAM modalities may benefit conventional medicine system. Likewise, most HCPs perceived different CAM therapies aseffective treatment options. More than 50% HCPs suggested CAM elective courses in the curriculum of the health sciences program.Overall, 79.17% of the HCPs have poor knowledge of CAM. Physicians have the highest knowledge score 25.63%, followed by pharmacists 21.99%, and nurses 12.26%. Knowledge status was significantly associated with age, profession, and experience of practice (p = 0.001,0.001 & 0.019). CONCLUSION: This study revealed that despite the overall positive attitude of HCPs toward CAM, the score of knowledge is low. Therefore, the survey recommends evidence-based guidelines for the rationale use of CAM and updated syllabi of undergraduate health programs which will assist the future HCPs in increasing professionals' knowledge toachieve better health outcomes for the general public.

Development of chitosan based ß-carotene mucoadhesive formulation for skin cancer treatment.

Mucopermeating nanoformulations can enhance mucosal penetration of poorly soluble drugs at their target site. In this work, thiolated chitosan (TCS)-lithocholic acid (LA) nanomicelles loaded with ß-carotene, a safe phytochemical with anticancer properties, were designed to improve the pharmaceutical and pharmacological drug profile. The TCS-LA nanomicelles were characterized by FTIR to confirm the presence of the thiol group that favors skin adhesion, and to corroborate the conjugation of hydrophobic LA with hydrophilic CS to form an amphiphilic polymer derivative. Their crystalline nature and thermal behavior were investigated by XRD and DSC analyses, respectively. According to DLS and TEM, their average size was <300 nm, and their surface charge was +27.0 mV. ß-carotene entrapment and loading efficiencies were 64 % and 58 %, respectively. In vitro mucoadhesion and ex vivo mucopenetration analyses further corroborated the potential of the nanoformulation to deliver the drug in a sustained manner under conditions mimicking cancer micro-environment. Anticancer studies in mice demonstrated that the loaded nanomicelles delayed skin cancer growth, as revealed by both morphological and biochemical parameters. Based on the results obtained herein, it can be concluded that drug-loaded TCS-LA is a novel, stable, effective and safe mucoadhesive formulation of ß-carotene for the potential treatment of skin cancer.

Potential and weak links in the management of tuberculosis by Pakistani private pharmacy staff.

Introduction: The emergence of MDR-TB is a global threat and an obstacle to the effective control of TB in Pakistan. A lack of proper TB knowledge among the staff in private pharmacies and the sale of compromised quality anti-TB drugs are the main instigators of multidrug-resistant tuberculosis (MDR-TB). Thus, this study was aimed at investigating the quality and storage conditions of fixed-dose combination (FDC) anti-TB drugs along with the awareness of staff working in private pharmacies regarding the identification of potential patients with TB and dispensing the inappropriate treatment regimens contributing to MDR-TB. Methods: The study is completed in two phases. In phase I a cross-sectional study is performed using two quantitative research designs, i.e., exploratory and descriptive, to evaluate the knowledge of private pharmacy staff. The sample of 218 pharmacies was selected. While in phase II cross sectional survey is conducted in 10 facilities from where FDC anti TB drugs were sampled for analyzing their quality. Result: Results revealed the presence of pharmacists only at 11.5% of pharmacies. Approximately 81% of staff at pharmacies had no awareness of MDR-TB, while 89% of pharmacies had no TB-related informative materials. The staff identified that most of the patients with TB (70%) were of poor socio-economic class, which restricted their purchase of four FDCs only up to 2-3 months. Only 23% were acquainted with the Pakistan National TB Program (NTP). Except for MDR-TB, the results showed a significant correlation between the experiences of staff with TB awareness. Findings from the quality evaluation of four FDC-TB drugs indicated that the dissolution and content assay of rifampicin were not according to the specifications, and overall, 30% of samples failed to comply with specifications. However, the other quality attributes were within the limits. Conclusion: In light of the data, it can be concluded that private pharmacies could be crucial to the effective management of NTP through the timely identification of patients with TB, appropriate disease and therapy-related education and counseling, and proper storage and stock maintenance.

Emulgel-loaded mannosylated thiolated chitosan-coated silver nanoparticles for the treatment of cutaneous leishmaniasis.

Topical treatment of cutaneous leishmaniasis holds great promise for decreasing drug associated side effects and improving efficacy. This study was aimed to develop mannosylated thiolated chitosan-coated silver nanoparticles (MTCAg) loaded emulgel for the treatment of cutaneous leishmaniasis. MTC-Ag were synthesized via a chemical reduction method and were loaded into the emulgel. The nanoparticles had a zeta potential of +19.8 mV, an average particle size of 115 nm and a narrow polydispersity index of 0.26. In-vitro release profiles showed controlled release of silver ions from both the MTC-Ag and the emulgel-loaded MTC-Ag nanoparticles after 24 h. An ex-vivo retention study indicated 5 times higher retention of silver by the emulgel-loaded MTC-Ag than by the MTC-Ag nanoparticles. The in-vitro anti-leishmanial assay revealed that MTC-Ag had an excellent inhibitory effect on intracellular amastigotes, leading to ~90 % inhibition at the highest concentration tested. A 4-fold reduction in the IC50 value was found for MTC-Ag compared to blank Ag nanoparticles. Cytotoxicity assay showed 83 % viability of macrophages for MTC-Ag and 30 % for Ag nanoparticles at a concentration of 80 µg/mL, demonstrating the improved biocompatibility of the polymeric nanoparticles. Drug release and retention studies corroborate the great potential of MTC-Ag-loaded emulgel for the treatment of cutaneous leishmaniasis.

Amidated Pluronic Decorated Muco-Penetrating Self-Nano Emulsifying Drug Delivery System (SNEDDS) for Improved Anti-Salmonella typhi Potential.

The enteric system residing notorious Salmonella typhimurium (S. typhi) is an intracellular, food-borne, and zoonotic pathogen causing typhoid fever. Typhoid fever is one of the leading causes of mortality and morbidity in developing and underdeveloped countries. It also increased the prevalence of multidrug resistance globally. Currently, available anti-bacterial modalities are unable to penetrate into the intracellular compartments effectively for eradicating S. typhi infection. Therefore, in this study, we developed nanostructured lipid-based carriers in the form of a self-nanoemulsifying drug delivery system (SNEDDS) for targeted delivery of ciprofloxacin (CIP) into the S. typhi intracellular reservoirs. Capryol 90, Tween 80, and Span 20 were finalized as suitable oil, surfactant, and co-surfactant, respectively, according to the pseudoternary phase diagram emulsifying region. Targeting capability and mucopenetration of the SNEDDS was attributed to the inclusion of amidated pluronic (NH2-F127). Developed NH2-F127 SNEDDS were characterized via physicochemical, in vitro, ex vivo, and in vivo evaluation parameters. The size of the SNEDDS was found to be 250 nm, having positively charged zeta potential. In vitro dissolution of SNEDDS showed 80% sustained release of CIP in 72 h with maximum entrapment efficiency up to 90% as well as good hemocompatibility by showing less than 0.2% hemolysis and 90% biocompatibility. The survival rate of S. typhi in macrophages (RAW 264.7) was minimal, i.e., only 2% in the case of NH2-F127 SNEDDS. Macrophage uptake assay via nanostructures confirmed the maximum cellular uptake as evidenced by the highest fluorescence. Biofilm dispersion assay showed rapid eradication of developed resistant biofilms on the gall bladder. In vivo pharmacokinetics showed improved bioavailability by showing an increased area under the curve (AUC) value. Taken together, NH2-F127-SNEDDS can be utilized as an alternative and efficient delivery system for the sustained release of therapeutic amounts of CIP for the treatment of S. typhi.

Evaluation and Optimization of Prolonged Release Mucoadhesive Tablets of Dexamethasone for Wound Healing: In Vitro-In Vivo Profiling in Healthy Volunteers.

The aim of the projected study was to design and develop a novel strategy for evaluating the mucoadhesive potential of polymeric tablets of dexamethasone (DXM) for local delivery against wounds. Therefore, formulations (Q1-Q7) were synthesized via direct compression method by varying the concentrations of polymers, i.e., ethyl cellulose (EC) and agar extract (AG). Moreover, the mucoadhesive polymeric tablets were characterized via physicochemical, in vitro, ex vivo and in vivo experiments. However, physicochemical characteristics such as FTIR showed no interaction with different polymeric combination. Surface pH of all formulations was normal to slightly alkaline. Highest hydration of up to 6.22% and swelling index was comprehended with maximum concentration of AG (50% of total tablet weight). Whereas, ex vivo and in vivo residence time and mucoadhesion were attributed to the increased concentrations of polymers. Moreover, Q7, (optimized formulation), containing 10% of EC and 40% of AG, exhibited maximum release of DXM (100%) over 8 h, along with sufficient mucoadhesive strength up to 11.73 g, following first-order kinetics having r2 value of 0.9778. Hemostatic effects and epithelialization for triggering and promoting wound healing were highly pronounced in cases of Q7. Furthermore, in vivo residence time was 7.84 h followed by salivary drug concentration (4.2 µg/mL). However, mucoadhesive buccal tablets showed stability for 6 months, thus following the standardization (ICH-Iva) stability zone. In summary, DXM mucoadhesive tablets seem to be an ideal candidate for eradication of wound infections via local targeted delivery.

Stimuli-sensitive drug delivery systems for site-specific antibiotic release.

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.

Thiolated Chitosan Microneedle Patch of Levosulpiride from Fabrication, Characterization to Bioavailability Enhancement Approach.

In this study, a first attempt has been made to deliver levosulpiride transdermally through a thiolated chitosan microneedle patch (TC-MNP). Levosulpiride is slowly and weakly absorbed from the gastrointestinal tract with an oral bioavailability of less than 25% and short half-life of about 6 h. In order to enhance its bioavailability, levosulpiride-loaded thiolated chitosan microneedle patches (LS-TC-MNPs) were fabricated. Firstly, thiolated chitosan was synthesized and characterized by nuclear magnetic resonance (1HNMR) spectroscopy, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD). Thiolated chitosan has been used in different drug delivery systems; herein, thiolated chitosan has been used for the transdermal delivery of LS. LS-TC-MNPs were fabricated from different concentrations of thiolated chitosan solution. Furthermore, the levosulpiride-loaded thiolated chitosan microneedle patch (LS-TC-MNP) was characterized by FTIR spectroscopic analysis, scanning electron microscopy (SEM) study, penetration ability, tensile strength, moisture content, patch thickness, and elongation test. LS-TC-MNP fabricated with 3% thiolated chitosan solution was found to have the best tensile strength, moisture content, patch thickness, elongation, drug-loading efficiency, and drug content. Thiolated chitosan is biodegradable, nontoxic and has good absorption and swelling in the skin. LS-TC-MNP-3 consists of 100 needles in 10 rows each with 10 needles. The length of each microneedle was 575 µm; they were pyramidal in shape, with sharp pointed ends and a base diameter of 200 µm. The microneedle patch (LS-TC-MNP-3) resulted in-vitro drug release of 65% up to 48 h, ex vivo permeation of 63.6%, with good skin biocompatibility and enhanced in-vivo pharmacokinetics (AUC = 986 µg/mL·h, Cmax = 24.5 µg/mL) as compared to oral LS dispersion (AUC = 3.2 µg/mL·h, Cmax = 0.5 µg/mL). Based on the above results, LS-TC-MNP-3 seems to be a promising strategy for enhancing the bioavailability of levosulpiride.

HPLC method development and validation for in vitro and in vivo quantification of vancomycin in rabbit plasma.

Vancomycin (VAN) is an effective antibiotic due to its broad-spectrum bactericidal action. High performance liquid chromatography (HPLC), a powerful analytical technique is used for the in vitro/ in vivo quantification of VAN. The current study was aimed to detect the VAN from in vitro as well as the plasma after the extraction from blood of rabbits. The method was developed and validated according to International Council on Harmonization (ICH) Q2 R1 guidelines. Results showed that the peak of VAN was recorded at 2.96 and 2.57 min, respectively in vitro and serum. The coefficient of VAN turned out to be >0.9994 each for in vitro and in vivo samples. VAN was found linear in the range of 6.2-25000ng/mL. The values of accuracy and precision in terms of coefficient of variation (CV) were less than 2%, indicating the validity of the method. The values for LOD and LOQ were estimated to be 1.5 and 4.5ng/mL, correspondingly, which were lower than the values calculated from in vitro media. Furthermore, the score of the greenness found out to be 0.81, depicting good score using AGREE tool. It was concluded that the developed method was found accurate, precise, robust, rugged, linear, detectable and quantifiable at prepared analytical concentrations and could be used for in vitro and in vivo VAN determination.

A Multifunctional Polymeric Micelle for Targeted Delivery of Paclitaxel by the Inhibition of the P-Glycoprotein Transporters.

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 ± 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.

Polyethylene imine conjugated supramolecular stereocomplexed nanomicelles for intracellular delivery of rifampicin against Mycobacterium bovis.

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 Hyaluronic Acid Functionalized Self-Nano-Emulsifying Drug Delivery System (SNEDDS) for Enhancement in Ciprofloxacin Targeted Delivery against Intracellular Infection.

Ciprofloxacin (CIP), a potent anti-bacterial agent of the fluroquinolone family, shows poor solubility and permeability, thus leading to the development of intracellular pathogens induced multi-drug resistance and biofilms formation. To synergistically improve the biopharmaceutical parameters of CIP, a hyaluronic acid (FDA approved biocompatible polymer) functionalized self-nano emulsifying drug delivery system (HA-CIP-SNEDDS) was designed in the present study. SNEDDS formulations were tested via solubility, droplet size, zeta potential, a polydispersity index, thermodynamic stability, surface morphology, solid-state characterization, drug loading/release, cellular uptake, and biocompatibility. The final (HA-CIP-SNEDDS) formulation exhibited a mean droplet size of 50 nm with the 0.3 poly dispersity index and negative zeta potential (-11.4 mV). HA-based SNEDDS containing CIP showed an improved ability to permeate goat intestinal mucus. After 4 h, CIP-SNEDDS showed a 2-fold and HA-CIP-SNEDDS showed a 4-fold permeation enhancement as compared to the free CIP. Moreover, 80% drug release of HA-CIP-SNEDDS was demonstrated to be superior and sustained for 72 h in comparison to free CIP. However, anti-biofilm activity of HA-CIP-SNEDDS against Salmonella typhi was higher than CIP-SNEDDS and free CIP. HA-CIP-SNEDDS exhibited increased biocompatibility and improved oral pharmacokinetics as compared to free CIP. Taken together, HA-CIP-SNEDDS formulation seems to be a promising agent against Salmonella typhi with a strong targeting potential.

Enhanced solubility and biopharmaceutical performance of atorvastatin and metformin via electrospun polyvinylpyrrolidone-hyaluronic acid composite nanoparticles.

The study was aimed to improve the aqueous solubility of atorvastatin (AT) and ameliorate permeability of metformin (MT) in a combination formulation, improving their oral bioavailability. Several AT-MT loaded polyvinylpyrrolidone (PVP) and hyaluronic acid (HA) based nanoparticles were prepared through electrospraying method (ES-NPs), and tested for physicochemical, in vitro, and in vivo parameters. Among the trialed formulations, a sample consisting of AT, MT, PVP, and HA at the weight ratio of 1/6.25/3.75/15 furnished the most satisfying solubility and release rate results. It enhanced approximately 10.3-fold and 3.6-fold solubility of AT as compared with AT powder and marketed product (Lipilow) in phosphate buffer pH = 6.8, respectively. Whereas, permeation of MT was 1.60-fold and 1.47-fold improved as compared with MT powder and marketed product (Glucophage), respectively. As compared with Lipilow, AUC (0-∞) and Cmax of AT with ES-NPs in rats were improved to 3.6-fold and 3.2-fold, respectively. Similarly, as compared with Glucophage, AUC (0-∞) and Cmax of MT were improved to 2.3-fold and 1.8-fold, respectively. Thus, ES-NPs significantly enhanced the solubility of AT (a BCS class II drug) and permeability of MT (a BCS class III drug) and might be a promising drug delivery system for co-delivery of these drugs.

Tuberculosis Resistance and Nanoparticles: Combating the Dual Role of Reactive Oxygen Species in Macrophages for Tuberculosis Management.

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.

Green synthesized selenium doped zinc oxide nano-antibiotic: synthesis, characterization and evaluation of antimicrobial, nanotoxicity and teratogenicity potential.

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.

Amphotericin B Loaded Polymeric Nanoparticles for Treatment of Leishmania Infections.

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-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® 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.

Oral delivery and enhanced efficacy of antimonal drug through macrophage-guided multifunctional nanocargoes against visceral Leishmaniasis.

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.

Multi-functionalized nanocarriers targeting bacterial reservoirs to overcome challenges of multi drug-resistance.

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. Graphical abstract.

Formulation and evaluation of hyaluronic acid-based mucoadhesive self nanoemulsifying drug delivery system (SNEDDS) of tamoxifen for targeting breast cancer.

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.

Development and Characterization of Bioadhesive Film Embedded with Lignocaine and Calcium Fluoride Nanoparticles.

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. Graphical Abstract.