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The aim of this study is to evaluate and compare the oral bioavailability of nanonized progesterone (nano-PG) and micronized progesterone (micro-PG) sustained release tablet formulation in healthy and pregnant rabbits. High pressure compressed gas technology reduces the particle size from 1.72 ± 2.5 μm (micro-PG) to 800 ± 35 nm (nano-PG). DSC and XRD showed that both micro-PG and nano-PG were crystalline and exist as form I. Higher melting enthalpy of nano-PG indicated improved drug stability whereas XRD showed slight reduction in degree of crystallanity following nanonization. Nano-PG demonstrated 2-fold higher solubility in SDS aqueous solution and significantly higher permeability (p < 0.05) across porcine intestine compared to micro-PG. The pharmacokinetics of nano-PG and micro-PG was conducted in healthy and pregnant rabbits. The Cmax of nano-PG was higher in healthy and pregnant rabbits however the difference was significant in healthy rabbits only. The nano-PG demonstrated 30% and 18% higher bioavailability compared to micro-PG in healthy and pregnant rabbits, respectively. In conclusion, nanonization improves solubility, dissolution and bioavailability of PG in rabbits without affecting solid state characters.

Background: 5-Fluorouracil (5-FU) is a well-established anticancer drug. Several studies have also demonstrated the anticancer potential of Cannabidiol (CBD) against various malignancies, including skin cancer. Reported synergistic effects of this combination fascinate researchers to consider this for the management of skin cancer. Methods: A simple and robust HPLC method for simultaneous estimation of 5-FU and CBD at its single wavelength (237 nm) was developed and validated. The separation of these compounds was performed on Waters® HPLC system with Hypersil™ C18 RP-column using methanol and water in gradient flow as mobile phase. The method could effectively quantify the nanogram levels of both analytes simultaneously in plasma spiked samples and various nanoformulations. The analytical performance of the proposed method was validated in terms of various parameters, such as linearity, ruggedness, specificity, and few others. Results: 5-FU as well as CBD were successfully detected at 237 nm with retention time 1.4 and 1.84 minutes respectively. Calibration curves were found to be linear with R2 values of 0.985 and 0.984 for 5-FU and CBD respectively. The method was linear, precise, specific and robust. Additionally, prepared method successfully employed in determining concentration of both drugs in combitorial nanoformulations. Conclusion: The findings show that the developed method was simple, reliable, sensitive and economical. It could be employed for the simultaneous estimation of 5-FU and CBD in various in vitro and in vivo studies.

Electrospinning is a versatile and viable technique for generating ultrathin fibers. Remarkable progress has been made in techniques for creating electro-spun and non-electro-spun nanofibers. Nanofibers were the center of attention for industries and researchers due to their simplicity in manufacture and setup. The review discusses a thorough overview of both electrospinning and non-electrospinning processes, including their setup, fabrication process, components, and applications. The review starts with an overview of the field of nanotechnology, the background of electrospinning, the surge in demand for nanofiber production, the materials needed to make nanofibers, and the critical process variables that determine the characteristics of nanofibers. Additionally, the diverse applications of electrospun nanofibers, such as smart mats, catalytic supports, filtration membranes, energy storage/heritage components, electrical devices (batteries), and biomedical scaffolds, are then covered. Further, the review concentrates on the most recent and pertinent developments in nanofibers that are connected to the use of nanofibers, focusing on the most illustrative cases. Finally, challenges and their possible solutions, marketing, and the future prospects of nanofiber development are discussed.

In modern world, Pharma sector observes steep increase in demand of personalized medicine. Various unique ideas and technology were proposed and implemented by different researchers to prepare personalized medicine and devices. 3-dimensional printing (3DP) is one of the revolutionary technologies which can be used to prepare tailored medicine via CAD (Computer Aided Design) software. 3DP allows researchers to manufacture customized dosage form with desired modifications in geometry which would in turn alter dosage behaviour of the product with reduced side effects. Current achievement of 3DP includes personalized and adjustable dosage form, multifunction drug delivery systems, medical devices, phantoms, and implants specific to patient anatomy. Additionally, 3DP is employed for preparing tailored regenerative medicines. This review focuses on 3DP use in pharmaceuticals including drug delivery systems and medical devices with their method of fabrication. Additionally, different clinical trials as well as different patents done till date are cited in the paper. Furthermore, regulatory issues and future perspective related to 3 D printing is also well discussed.

The CAD (Computer-aided design) and CAM (computer-aided manufacturing) have most applications in the manufacturing of fully automated, personalized dental devices and tailor-made treatment plans. 3D printing is one of the most rapidly expanding and new methods of manufacturing different things because of its on-demand and high productivity within the cost-effective manner which have a variety of applications in healthcare, pharmaceuticals, orthopaedics, engineered tissue models, medical devices, defence industries, automotive and aerospace sectors. Due to its emerging applications in the various sectors, the healthcare, Industries, and academic sectors are attracted towards the 3D printed materials. This review talks about the dental implants, polymers that are employed in concocting dental implants, critical parameters, and challenges which are to be considered while preparing these implants, advantages of 3D printing in the field of dentistry and the current trends. it discusses the variety of applications of 3D printed materials in the field of dentistry. Along with their method of fabrication, their critical process parameters (CPPs) are also discussed.

Punicalagin is the most bioactive polyphenols of pomegranate with high antioxidant, FRS activity. It has the potential to cure different ailments related to the CVS system. The current research work was envisioned to predict the targeting efficiency of punicalagin (PG) nanoparticles to the macrophages, more specifically to bone marrow macrophages. For this, we selected mannose decorated PLGA-punicalagin nanoparticles (Mn-PLGA-PG) and before formulating this nanocarrier in laboratory settings, we predict the targeting efficiency of this nanocarrier by in-silico analysis. Authors initiated in-silico analysis on macrophage mannose receptor to be acquainted with the binding affinity, the interaction of PG based nanocarrier (MnPLGA-PG) to this receptor. In-silico docking studies of macrophage mannose receptor and PG showed binding interaction on its surface with a docking score of -4.00. PG interacts with hydrogen bonds to the charged residue ASP668 and GLY666 and polar residue GLN760 residue of Mn receptor. Mannose with a docking score of -5.811 and interacting with four hydrogen bonds to the mannose receptor of macrophage with two negatively charged residues GLU706, GLU719 also with two hydrophobic residues VAL716, PHE708. And in PLGA, it showed a - 4.334 docking score and interacts with three hydrogen bonds, LYS739 (positively charged), HIS692 (polar), and LEU694 (hydrophobic)..In trajectory analysis, while stabilizing the structure till 100ns the complex RMSD of macrophage, Mn receptor-PG found within the range of 4.6 Å. Initial fluctuations in RMSD noticed to 4.95 Å at 20ns which started stabilizing after words with timescale. In the total of 100ns, initially up to 40ns the PG (ligand) deviated to 1.2Å. After 40ns, it was noted that the ligand RMSD was almost constant and started stabilizing with 1.03Å at 100ns. Findings depict that this nanocarrier could be a promising lead molecule to regulate the incidence of drug induced neutropenia.

Introduction Ziprasidone (ZP) is a novel atypical antipsychotic agent effective in the treatment of positive and negative symptoms of schizophrenia with low chances for extrapyramidal side effects (EPs) and cognitive deficits. ZP possesses poor oral bioavailability (~50%), short biological half-life (~2.5 h) and due to extensive first-pass metabolism, a repeated dose is administered which makes the therapy non-adherent, leading to patient non-compliance. Therefore, this is a first report of developing parenteral ZP loaded sustained release phospholipid based phase-transition system (ZP-LPS). Methods The ZP-LPS system was formulated by mixing of biocompatible materials including phospholipid E 80, medium chain triglyceride (MCT) and ethanol. Optimization was done by aqueous titration method using pseudo-ternary phase diagram and dynamic rheological measurements. In vivo depot formation was confirmed by gamma scintigraphy after subcutaneous injection. Biodegradation and biocompatibility studies were performed for its safety evaluation. Finally, the efficacy of the formulation was assessed by Morris water maze (MWM) test and dizocilpine (MK-801) was used to induce schizophrenia in Sprague-Dawley rats. Results Optimized ZP-LPS showed rapid gelation (2 min), highest change in viscosity (~48000 mPa.s) and sustained release of ZP over a period of 1 month. Gamma scintigraphy depicted that the low-viscosity ZP-LPS system undergo rapid in situ gelation. Biodegradation and biocompatibility studies revealed gradual degradation in size of depot over a period of 28 days without any inflammation at the injection site. In MWM test, escape latency, time spent and total distance in target quadrant were significantly improved (p < 0.001) in the ZP-LPS group in comparison to the MK-801 group when evaluated at day 0, day 7 and day 28. However, significant improvement (p < 0.001) was observed only at day 0 in ZP suspension group. Conclusion The overall result indicates that the novel ZP-LPS system is safe, biodegradable, and effective for the management of schizophrenia.

Biomimetic nanotechnology could serve as an advancement in the domain of drug delivery and diagnosis with the application of natural cell membrane or synthetically-derived membrane nanoparticles (NPs). These biomimetic NPs endow significant therapeutic and diagnostic efficacy by their unique properties, such as immune invasion and better targeting ability. Additionally, these NPs have a unique ability to retain the inherent properties of cell membrane and membrane's intrinsic functionalities, which helps them to exhibit superior therapeutic effects. In this review, we describe how these membrane-clocked NPs endow superior therapeutic effects by immune invasion; along with this, the development of membrane-coated NPs and their method of preparation and characterization has been clearly described in the manuscript. Moreover, Various developed membrane-coated NPs such as red blood cell membrane-coated NPs, white blood cells membrane-coated NPs, platelet membrane coated, cancer cell membrane coated, bacterial membrane vesicles and, mesenchymal stem cells membrane-coated NPs have been established in this manuscript. At last, the discussion on the role of membrane-coated NPs as theranostics, and notably, the literature that demonstrates the shreds of evidences of these NPs in targeting and neutralizing the SARS-CoV-2 virus have also been incorporated.

Naloxone is an opioid receptor antagonist that can eradicate all pre-indications of the toxicity and inverse the opioid overdose. However, oral administration of naloxone offers limitations such as its extensive first-pass metabolism that results in poor therapeutic effects. In order to resolve this issue, we developed intranasal solid-lipid nanoparticles in which naloxone was incorporated for the higher brain disposition of naloxone with superior therapeutic effects for the reversal of toxicity of opioid overdose. The preparation of naloxone loaded solid-lipid nanoparticles was done by employing the solvent evaporation method. Later, the designed formulation was optimized by Quality by Design approach, specifically, Box-Behnken method. The composition of optimized formulation was Glyceryl monostearate as a solid lipid (40 mg), Pluronic127 (0.5%) and Tween 80 (0.1%) as a surfactant and co-surfactant, respectively. Furthermore, the characterization of optimized formulation was achieved in terms of particle size, PDI, zeta potential, entrapment efficiency, and drug loading which were 190.2 nm, 0.082, −16 mV, 95 ± 0.532% and 19.08 ± 0.106%, respectively. Afterwards, in vitro, ex vivo and in vivo experiments were performed in which higher drug release and superior drug uptake by nasal membrane were observed for naloxone-loaded solid-lipid nanoparticles, later it was confirmed by confocal microscopy of ex vivo nasal membrane tissue. The findings of gamma scintigraphy investigation exhibited better deposition of naloxone-loaded solid-lipid nanoparticles as compared to naloxone solution. Also, the better deposition of naloxone by gamma scintigraphy was further validated by the investigation through the biodistribution study. Additionally, the key findings of the pharmacokinetic study revealed Cmax, Tmax, AUC0-t, AUC0-∞, T1/2 and Ke was found to be 163.95 ± 2.64 ng/ml, 240 ± 2.1 min, 17.75 ± 1.08 ng.hr/ml, 18.82 ± 2.51 ng.hr/ml, 70.71 ± 0.115 min, 0.098 ± 0.01 h−1 respectively. Lastly, investigations such as weight variation and histopathological proved the plausible potential of naloxone-loaded solid-lipid nanoparticles in terms of safety as no toxicity was noticed even after the administration of the three-folds dose of the normal dose. Therefore, considering all these findings, it could be easy to say that these developed naloxone-loaded solid-lipid nanoparticles could be administrated via intranasal route and can act as successful novel nanoformulation for the effective treatment of opioid overdose.

The present study aimed at the development and evaluation of tacrolimus gellan gum nanoparticles (TGNPs) for the effective management of dry eye disease (DED) following topical application. TGNPs were developed by ionotropic gelation between gellan gum and aluminum chloride. Developed TGNPs were nanosized (274.46 ± 8.90 nm) with high % encapsulation efficiency (74.2 ± 2.4%) and loading capacity (36.14 ± 1.7%). The nanosize and spherical morphology of TGNPs was confirmed by transmission electron microscopy (TEM) and atomic force microscopy (AFM). Fourier transform infrared spectroscopy (FTIR) revealed no interaction between drug and GG. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) confirms the conversion of crystalline tacrolimus to amorphous post encapsulation in the nanoparticle. TGNPs showed prolonged drug release throughout 12 h and higher pre-corneal retention compared to tacrolimus solution. HET-CAM studies, histopathological evaluation, and Draize test confirmed the safety of the formulation for ocular use. Further, the pharmacodynamic studies using experimental DED in rabbits showed that TGNPs are effective in treating symptoms of DED. In conclusion, topical delivery of TGNPs could hold potential for efficient management of DED.

Pain is a noxious stimulus caused due to tissue damage and varies from mild to severe. Nalbuphine (NLB) is an approved, inexpensive, non-controlled, opioid agonist/antagonist analgesic used worldwide in various clinical settings for pain management. The current study aims to formulate NLB loaded solid lipid nanoparticles (SLNs) using solvent injection technology. The morphological and chemical structure of the developed SLNs were characterized using Field Emission Scanning Electron Microscopy (FESEM), Transmission Electron Microscopy (TEM) and Fourier Transformation Infrared Spectroscopy (FTIR). The results revealed from the point prediction confirmation in design expert software was the formulation of NLB-SLNs with an average particle size of (170.07 ± 25.1 nm), encapsulation efficiency (93.6 ± 1.5%) & loading capacity of 26.67%. The in-vitro permeation of developed NLB-SLNs was observed to be 94.18% at 8 h when compared with NLB solution whose maximum permeation was seen within 3 h of application. Efficacy of the formulation was also evaluated using eddy's hot plate method, where the onset of action started within 10 min of administration, and the maximum effect was observed at 1 h. The NLB-SLNs was screened for cytotoxicity in human embryonic kidney cells (HEK-293), and the dosage was considered safe when administered intranasally in animal since no detectable effect to the brain was observed. Biodistribution and gamma scintigraphy study of NLB-SLNs showed the prepared formulation reaching the target site, i.e. brain and was retained. Conclusively, the prepared NLB-SLNs formulation was safe and effective in producing an analgesic effect in vivo.