Manu Sharma

Background: Tapentadol is an effective centrally acting analgesic for treating neuropathic pain. However, its short half-life, high first-pass metabolism, and requirement for frequent dosing limit its therapeutic effect and patient compliance. The purpose of the present innovation was to develop cost-effective tapentadol-loaded floating nanoparticles (TFNs) for sustained oral delivery. Methods: TFNs were prepared using the double emulsion solvent evaporation method. The effects of various formulation and process parameters, including polymer ratio, drug concentration, surfactant concentration and type, sonication time, and external phase volume were systematically studied. Analytical physicochemical characterization, morphology, buoyancy and drug release behavior were carried out. In vivo performance was evaluated by performing pharmacokinetic, tissue distribution, and pharmacodynamics studies in a chronic constriction injury model. Results: The optimized formulation exhibited spherical shape with nano-size (320.66 ± 17.50 nm), and good entrapment efficiency (82.85 ± 6.57%). Analytical characterization confirmed successful drug encapsulation and compatibility with formulation components. The engineered floating nanoparticulate architecture allowed both long gastric drug retention and a controlled drug release, governed by an anomalous diffusion-controlled mechanism. Pharmacokinetic evaluation revealed 3.36-fold higher relative oral bioavailability from TFNs. In addition, 1.49-fold higher drug availability in brain with TFNs was observed. Pharmacodynamic studies demonstrated a marked reduction in neuropathic pain responses, confirming the superior and prolonged analgesic effect of TFNs. Conclusions: The findings establish the developed TFNs as a promising controlled-release system for effective and sustained management of neuropathic pain. Even so, further studies focusing on large-scale production, long-term safety, and clinical evaluation are necessary before the formulation can be advanced for clinical application.

Intranasal gellan gum in-situ gel increases the therapeutic potential of caffeic acid in Alzheimer's disease by increasing nasal retention, direct transport to brain via nose and neuroprotection.

Despite the major advancements in cancer treatment, colon cancer (CC) is still one of the most lethal malignancies worldwide. Among various type of cancer, it is the third largest prevailing kind of cancer affecting both men and women equally. Metastatic development is particularly common in individuals with advanced stages and frequently associated with subpar response of chemotherapy and severe morbidity. The unfavorable effects of intense chemotherapy on normal cells and emergence of multidrug resistance are the two main reasons for treatment failure. Recent research in nanotechnology enables the use of advanced natural and synthetic biomaterials alone or in combination to target cancer cells with anticancer medications without affecting healthy cells. Anticancer drug laden nanocarriers improve the drug distribution, bioavailability and accumulation of cytotoxic therapeutic concentration at tumor site along with reduced side effects. Additionally, upon oral administration, polymeric vehicles shield the medication from premature release, degradation in upper gastrointestinal tract and facilitate controlled release at cancerous site of colon. Here, we primarily focus on the present situation and possible advantages of polymeric biomaterials either owned or in conjunction with other therapeutics to develop ideal drug carrier systems to treat colon carcinoma.

Bromelain-loaded nanocarriers enhance oral bioavailability and therapeutic efficacy of bromelain in the management of allergic asthma.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease marked by inflammation of synovium and generation of autoantibodies. Bone and cartilage are frequently damaged along with weakening of tendons and ligaments resulting in disability. An effective RA treatment needs a multi-disciplinary approach which relies upon pathophysiology that is still partially understood. In RA patients, inflammation was induced by pro-inflammatory cytokines including IL-1, IL-6 & IL-10. The conventional dosage regimens for treating RA have drawbacks such as ineffectiveness, greater doses, frequent dosing, relatively expensive and serious adverse effects. To formulate an effective treatment plan for RA, research teams have recently focused on producing several nanoformulations containing anti-inflammatory APIs with an aim to target the inflamed area. Nanomedicines have recently gained popularity in the treatment of RA. Interestingly, unbelievable improvements have been observed in current years in diagnosis and management of RA utilizing nanotechnology. Various patents and clinical trial data have been reported in relevance to RA treatment.

A feasible nano transdermal delivery system generally intends to have specific ideal and distinct characteristics primarily for safety, clinical efficacy, and boosted therapeutic index. The delivery of drugs, particularly macromolecules, across the skin is one of the most strenuous obstacles in front of pharmaceutical scientists. Technology advancement has provided some opportunities to overcome this difficulty by utilising microneedle arrays, ablation, laser methods etc. However, associated uneasiness, painful sensation, and higher cost of therapies limit their day-today use. Therefore, researchers have focused on developing alternate carriers like ultra-deformable liposomes, also termed transfersomes. Transfersomes are composed of a lipid bilayer containing phospholipids and an edge activator to facilitate drug delivery via transdermal route to deeper layers of skin and for higher systemic bioavailability. The bilayer structure of transfersomes allows ease of encapsulation of both hydrophilic and lipophilic drugs with higher permeability than typical liposomes. Therefore, among various vesicular systems, transfersomes have developed much interest in targeted and sustained drug delivery. The current review primarily emphasizes critical aspects of transfersomes, including their applications, clinical trial studies, and patents found in various literature sources.

The current study aims to improve clarithromycin bioavailability and effectiveness in complicated intra-abdominal infection management. Therefore, clarithromycin-loaded submicron dual lipid carriers (CLA-DLCs) were developed via hot high shear homogenization technique and evaluated for colloidal parameters, release behavior, stability study, and in-vitro antibiofilm activity. Bioavailability and therapeutic efficacy of optimized formulation on hampering cytokines storm induction was determined in E. coli-induced peritonitis. The developed CLA-DLCs (particle size 326.19 ± 24.14 nm, zeta potential −31.34 ± 2.81 mV, and entrapment efficiency 85.78 ± 4.01%) exhibited smooth spherical shapes and sustained in vitro release profiles. Long-term stability study of optimized CLA-DLCs ensured maintenance of colloidal parameters for 1 year at room temperature. In vitro antimicrobial studies revealed 3.43-fold higher anti-biofilm activity of CLA-DLCs compared with clarithromycin. In addition, the relative bioavailability of CLA-DLCs was enhanced 5.89-fold compared to pure drug in rats. The remarkable decrease in microbial burden in blood as well as tissues, along with oxidative stress markers (lipid peroxidation, myeloperoxidase activity, and carbonylated protein level) and immunological markers (total leukocyte count, neutrophil migration, NO, TNF-, and IL-6) on treatment with CLA-DLCs enhanced the survival in a rat model of peritonitis compared with the pure drug and untreated groups. In conclusion, CLA-DLCs hold promising potential in management of intra-abdominal infections and prevention of associated complications.