Evolving Role of Natural Products from Traditional Medicinal Herbs in the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease that causes dementia by impairing mental capacity growth and disrupting neurocognitive activity. Despite recent advancements in AD therapy, therapeutic effectiveness has been small, noncurative, and susceptible to drug resistance. The reality that AD's origin remains unknown and that the blood-brain barrier limits treatment effectiveness are two significant impediments to science. Plants are repositories for novel chemical entities, which provide an exciting avenue for Alzheimer's disease studies. Although several herbal remedies are unquestionably efficient, only a small number have been clinically tested for their active chemical constituents and biological activities. Using published data in the literature, we summarized commonly used medicinal plants and herbs and their phyto components for the care and diagnosis of Alzheimer's disease as an alternative therapy. In this, we summarize the main compounds found in 30 different herbal medicines that target neurodegenerative diseases. Using the experimental study of physicochemical properties, we put forward a hypothesis about potential medicinal plants and the management of Alzheimer's disease. The summary analysis demonstrates that conventional herbal medicines produce compounds with physicochemical properties with a high degree of similarities with existing approved medicines.

The emerging role of immune checkpoint inhibitors in the treatment of triple-negative breast cancer.

Triple-negative breast cancers (TNBCs) form a heterogeneous group of breast carcinomas that lack expression of estrogen receptor, progesterone receptor and epidermal growth factor receptor 2. In the past decade, immune checkpoint inhibitors (ICIs) have revolutionized the arena of cancer immunotherapy. Early results are now accumulating from trials involving the treatment of TNBCs with radical ICIs therapies, including combinational therapies that include ICI technologies. In this review, we provide a broad overview of the progress of immunotherapy-based treatments and discuss future opportunities for their use in TNBC.

Polymeric Drug-Delivery Systems: Role in P-gp Efflux System Inhibition.

Permeability glycoprotein (P-gp), a multispecific drug transporter belonging to the multidrug resistance (MDR) gene subfamily, is mainly responsible for efflux of diffused intracellular drugs, resulting in poor drug bioavailability. P-gp is overexpressed in the blood-brain barrier, gastrointestinal tract (GIT), kidney, liver, pancreas, and cancerous cells, leading to multidrug resistance and failure of therapy. Because P-gp is transported into cells by way of receptor-mediated endocytosis (in contrast to diffusion for free drug), polymeric efflux pump modulators can have a major role in efficient drug delivery. Various polymer drug conjugates that have been proven to provide potential treatments in MDR cases are reviewed here, with an emphasis on the role of the P-gp efflux pump, bioavailability, and the mechanism of inhibition of the P-gp transporter by various polymers and delivery systems. This review also highlights the potential of specific polymer drug conjugates to act as P-gp efflux pump inhibitors to provide enhanced bioavailability and therapeutic efficacy.

Role of polymer-drug conjugates in organ-specific delivery systems.

Polymers have been utilized to deliver the drug to targeted site in controlled manner, achieving the high-therapeutic efficacy. Polymeric drug conjugates having variable ligands as attachments have been proved to be biodegradable, stimuli sensitive and targeted systems. Numerous polymeric drug conjugates having linkers degraded by acidity or intracellular enzymes or sensitive to over expressed groups of diseased organ/tissue have been synthesized during last decade to develop targeted delivery systems. Most of these organs have number of receptors attached with different cells such as Kupffer cells of liver have mannose-binding receptors while hepatocytes have asialoglycoprotein receptors on their surface which mainly bind with the galactose derivatives. Such ligands can be used for achieving high targeting and intracellular delivery of the drug. This review presents detailed aspects of receptors found in different cells of specific organ and ligands with binding efficiency to these specific receptors. This review highlights the need of further studies on organ-specific polymer-drug conjugates by providing detailed account of polymeric conjugates synthesized till date having organ-specific targeting.

N-succinyl chitosan as buccal penetration enhancer for delivery of herbal agents in treatment of oral mucositis.

Oral mucositis is one of the major side effects of cancer chemotherapy (30-76%) and radiotherapy (over 50%). Current palliative treatments of oral mucositis include specialized agents like pelifermin, platelet derived factors etc. or oral hygienic agents which suffered from various drawbacks like systemic side effect, least effect owing to fast wash out of buccal mucosa, patient unfriendly delivery systems, and mere symptomatic relief. In this research work, N-succinyl chitosan gel delivery system of microemulsified eugenol, honey and sodium hyaluronate was prepared to explore their multiple and synergistic effects on various pathological factors of oral mucositis. N-succinyl chitosan was synthesized in our laboratory and loaded with microemulsified eugenol (10% v/v), honey (10% v/v) and sodium hyaluronate (0.2% w/v) to prepare orogel with optimum pH, spreadability, mucoadhesion strength, and viscosity. In vitro eugenol release from N-succinyl chitosan gel after 8 hours in PBS (pH-6.4) was found to be 87.45±0.14%, which was better in comparison to that released from chitosan gel. Ex vivo penetration studies using rat buccal mucosal tissue also suggested better J-efflux of eugenol through N-succinyl chitosan in comparison to chitosan gel with enhancement ratio (ER) of 1.71. The antimicrobial effect of N-succinyl chitosan based orogel against S. aureus and C. albicans efficacy was found to be statistically high in comparison to chitosan based orogel as well as marketed formulation of chlorhexidine (p<0.05). The N-succinyl chitosan orogel in 5-fluoro uracil induced oral mucositis animal (Wistar rats) model showed enhanced survival ratio, weight gain and high tissue regeneration activity than chitosan gel formulation within 15 days. The formulation was successful in elevating the survival and reducing the inflammation in the oral mucosa of animals compared to disease control (p<0.05) and hence suggesting the potential of N-succinyl chitosan orogel in the treatment of oral mucositis.

Drug carrier systems for solubility enhancement of BCS class II drugs: a critical review.

Poor aqueous solubility impedes a drug's bioavailability and challenges its pharmaceutical development. Pharmaceutical development of drugs with poor water solubility requires the establishment of a suitable formulation layout among various techniques. Various approaches have been investigated extensively to improve the aqueous solubility and poor dissolution rate of BCS class II and IV drugs. In this literature review, novel formulation options, particularly for class II drugs designed for applications such as micronization, self-emulsification, cyclodextrin complexation, co-crystallisation, super critical fluid technology, solubilisation by change in pH, salt formation, co-solvents, melt granulation, and solid dispersion, liposomal/niosomal formulations, are discussed in detail to introduce biopharmaceutical challenges and recent approaches to facilitate more efficient drug formulation and development.

Chitosan-alginate microcapsules of amoxicillin for gastric stability and mucoadhesion.

Amoxicillin-loaded microcapsules were prepared by ionotropic gelation of sodium alginate (ALG) with chitosan (CS) in presence of calcium chloride as gastroretentive delivery system. The effect of pH, concentration of ALG, CS and calcium chloride, and drug : ALG ratio were optimized in this study for minimizing the degradation of drug in acidic environment and increasing the loading efficacy and mucoadhesive efficiency of microcapsules. The optimum condition for prepared CS-ALG microcapsules was 2%w/v ALG, 0.75%w/v CS (pH5.0), and 1.0% w/v calcium chloride. The resulting microcapsules had drug entrapment efficiency of 84% and average size of 840 mm. CS concentration significantly influenced particle size and encapsulation efficiency of CS-ALG microcapsules (P<0.05). Decrease in the drug: ALG ratio resulted in an increased release of amoxicillin in acidic media. The relative decomposition of drug after encapsulation in CS-ALG microcapsules was decreased to 20.7%, 41.9%, and 83.3% in 2, 4, and 8 hours, respectively.

Scaffold: a novel carrier for cell and drug delivery.

Scaffolds are implants or injects, which are used to deliver cells, drugs, and genes into the body. Different forms of polymeric scaffolds for cell/drug delivery are available: (1) a typical three-dimensional porous matrix, (2) a nanofibrous matrix, (3) a thermosensitive sol-gel transition hydrogel, and (4) a porous microsphere. A scaffold provides a suitable substrate for cell attachment, cell proliferation, differentiated function, and cell migration. Scaffold matrices can be used to achieve drug delivery with high loading and efficiency to specific sites. Biomaterials used for fabrication of scaffold may be natural polymers such as alginate, proteins, collagens, gelatin, fibrins, and albumin, or synthetic polymers such as polyvinyl alcohol and polyglycolide. Bioceramics such as hydroxyapatites and tricalcium phosphates also are used. Techniques used for fabrication of a scaffold include particulate leaching, freeze-drying, supercritical fluid technology, thermally induced phase separation, rapid prototyping, powder compaction, sol-gel, and melt moulding. These techniques allow the preparation of porous structures with regular porosity. Scaffold are used successfully in various fields of tissue engineering such as bone formation, periodontal regeneration, repair of nasal and auricular malformations, cartilage development, as artificial corneas, as heart valves, in tendon repair ,in ligament replacement, and in tumors. They also are used in joint pain inflammation, diabetes, heart disease, osteochondrogenesis, and wound dressings. Their application of late has extended to delivery of drugs and genetic materials, including plasmid DNA, at a controlled rate over a long period of time. In addition, the incorporation of drugs (i.e., inflammatory inhibitors and/or antibiotics) into scaffolds may be used to prevent infection after surgery and other disease for longer duration. Scaffold also can be used to provide adequate signals (e.g., through the use of adhesion peptides and growth factors) to the cells, to induce and maintain them in their desired differentiation stage, and to maintain their survival and growth. The present review gives a detailed account of the need for the development of scaffolds along with the materials used and techniques adopted to manufacture scaffolds for tissue engineering and for prolonged drug delivery.

Amoxicillin loaded chitosan-alginate polyelectrolyte complex nanoparticles as mucopenetrating delivery system for h. Pylori.

The present study has been undertaken to apply the concept of nanoparticulate mucopenetrating drug delivery system for complete eradication of Helicobacter pylori (H. pylori), colonised deep into the gastric mucosal lining. Most of the existing drug delivery systems have failed on account of either improper mucoadhesion or mucopenetration and no dosage form with dual activity of adhesion and penetration has been designed till date for treating H. pylori induced disorders. In the present study, novel chitosan-alginate polyelectrolyte complex (CS-ALG PEC) nanoparticles of amoxicillin have been designed and optimized for various variables such as pH and mixing ratio of polymers, concentrations of polymers, drug and surfactant, using 3(3) Box-Behnken design. Various studies like particle size, surface charge, percent drug entrapment, in-vitro mucoadhesion and in-vivo mucopenetration of nanoparticles on rat models were conducted. The optimised FITC labelled CS-ALG PEC nanoparticles have shown comparative low in-vitro mucoadhesion with respect to plain chitosan nanoparticles, but excellent mucopenetration and localization as observed with increased fluorescence in gastric mucosa continuously over 6 hours, which clinically can help in eradication of H. pylori.

Clinical aspects of acute post-operative pain management & its assessment.

Management of postoperative pain relieve suffering and leads to earlier mobilization, shortened hospital stay, reduced hospital costs, and increased patient satisfaction. An effective postoperative management is not a standardized regime rather is tailored to the needs of the individual patient, taking into account medical, psychological, and physical condition; age; level of fear or anxiety; surgical procedure; personal preference; and response to therapeutic agents given. The major goal in the management of postoperative pain is to minimize the dose of medications to lessen side effects & provide adequate analgesia. Postoperative pain is still under managed due to obstacles in implementation of Acute Pain Services due to insufficient education, fear of complications associated with available analgesic drugs, poor pain assessment and inadequate staff. This review reflects the clinical aspects of postoperative pain & its assessment & management with an emphasis on research for new analgesic molecules & delivery system.