Deciphering the modulatory role of apigenin targeting oncogenic pathways in human cancers

Cancer is a complicated malignancy controlled by numerous intrinsic and extrinsic pathways. There has been a significant increase in interest in recent years in the elucidation of cancer treatments based on natural extracts that have fewer side effects. Numerous natural product-derived chemicals have been investigated for their anticancer effects in the search for an efficient chemotherapeutic method. Therefore, the rationale behind this review is to provide a detailed insights about the anticancerous potential of apigenin via modulating numerous cell signaling pathways. An ingestible plant-derived flavonoid called apigenin has been linked to numerous anticancerous potential in numerous experimental and biological studies. Apigenin has been reported to induce cell growth arrest and apoptotic induction by modulating multiple cell signaling pathways in a wider range of human tumors including those of the breast, lung, liver, skin, blood, colon, prostate, pancreatic, cervical, oral, and stomach. Oncogenic protein networks, abnormal cell signaling, and modulation of the apoptotic machinery are only a few examples of diverse molecular interactions and processes that have not yet been thoroughly addressed by scientific research. Thus, keeping this fact in mind, we tried to focus our review towards summarizing the apigenin-mediated modulation of oncogenic pathways in various malignancies that can be further utilized to develop a potent therapeutic alternative for the treatment of various cancers.     

Development,optimization and characterization of glycyrrhetinic acid–chitosan nanoparticles of atorvastatin for liver targeting

Glycyrrhetinic acid-modified chitosan (mGA-suc-CTS) is used as liver-targeted carrier for drug delivery. In this study, nanoparticles were prepared by ionic gelation process, and glycyrrhetinic acid act as the targeting ligand. The structure of the product was confirmed by IR and NMR techniques. The main aim of this study was to deliver atorvastatin directly to the liver by using same conjugate and reduce the associated side-effects, i.e. hepatotoxicity at high dose. Characterization of the developed formulation was performed by differential scanning calorimetry, particle size measurements and cellular uptake studies. Release profile, pharmacokinetics studies and organ distribution studies showed that developed formulation shows a relative higher liver uptake. The optimized formulation showed increased plasma concentration than the CTS nanoparticles as well as plain drug and the accumulation in the liver was nearly 2.59 times more than that of obtained with the CTS nanoparticles. Pharmaceutical and pharmacological indicators suggested that the proposed strategy can be successfully utilized for liver targeting of therapeutics.     

QSAR modeling on dopamine D2 receptor binding affinity of 6-methoxy benzamides

QSAR modeling was performed on 58 (S) N-[(1-ethyl-2-pyrrolidinyl) methyl]-6-methoxy benzamides as dopamine (DA) D2 receptor antagonists to identify the structural requirements for DA D2 receptor binding affinity. The study pointed out that the presence of hydrophobic substituents at R3 position and electron-donating groups at R5 position increased the biological activity. Substitutions at phenyl ring favored the binding affinity of these benzamides. Ethyl group and iodine at R3 position were advantageous to the activity whereas nitro group at phenyl ring hindered the antagonistic activity.     

Development and Performance Evaluation of a High-Volume Ultrafine Particle Concentrator for Inhalation Toxicological Studies

This article presents the development and performance evaluation of a high-volume ultrafine particle concentrator. The ultrafine particle concentrator consists of several units, including a size-selective inlet; a condensational growth unit; a series of two virtual impactors (concentrators); a thermal size restoration device; an air cooler; and a size-selective outlet. Ambient ultrafine particles are condensationally grown to supermicrometer sizes and then are concentrated by a factor of 40 to 50 using a two-stage virtual impactor. Subsequently, ultrafine particle size distribution is restored, using a thermal method. The Harvard ultrafine concentrated ambient particle system (HUCAPS) delivers 58 lpm of concentrated aerosol that can be used for in vivo or in vitro inhalation toxicological studies. Overall, pressure drop through the system is only 2.2 kPa, which is adequately low for inhalation toxicological exposure tests. The performance of this system was evaluated using single-component artificial aerosols with a variety of physicochemical properties as well as ambient air. These experiments showed that for an optimum supersaturation ratio of 3.0, all ultrafine particles grow and get concentrated by about the same enrichment factor, regardless of their composition and surface properties.     

Inhaled insulin for diabetes mellitus.

PURPOSE: Pharmacokinetic and safety data related to the use of inhaled insulin for the management of diabetes mellitus are discussed. The various pulmonary insulin delivery systems under development are also reviewed. SUMMARY: Several pharmaceutical companies are developing pulmonary insulin delivery systems. These products fall into two main groups: solution and drug powder formulations, which are delivered through different patented inhaler systems. Exubera, a rapid-acting insulin in powder form, has been studied extensively in patients with type 1 and type 2 diabetes mellitus. The AERx Insulin Diabetes Management System delivers a liquid form of human insulin. Preliminary data indicate that patients converting from insulin injections to this system showed higher compliance to therapy, demonstrated by improved glycemic control. Other pulmonary insulin delivery systems, including ProMaxx, AIR, Spiros, and Technosphere, are also under investigation. In humans, inhaled regular insulin is more rapidly absorbed than insulin from the subcutaneous injection site. The efficiency of inhaled insulin is lower than that of subcutaneous injection because pulmonary delivery of insulin involves some loss of drug within the inhaler or mouth during inhalation. A concern of many clinicians is the possibility of long-term effects from the intraalveolar deposition of insulin within the lung, since insulin is known to have growth-promoting properties. The long-term safety of these products has not been established. CONCLUSION: Several inhaled insulin products are under development. If these products receive marketing approval, the pulmonary delivery of insulin may offer patients with diabetes an alternative to repeated insulin injections.     

Polymeric nanofibers: targeted gastro-retentive drug delivery systems

Background: Conventional oral dosage forms exhibit poor/low bioavailability due to incomplete release of drug and short residence time at the absorption site. Gastro-retentive drug delivery system (GRDDS) is particularly used to improve bioavailability of the drugs, which have narrow absorption window down in the levels of gastrointestinal tract and also to treat local disorders.

Purpose: The purpose of this review is to describe the utility of the nanofibers as gastro-retentive dosage form. From last few decades, formulation scientists have put extensive efforts to develop suitable gastro-retentive drug delivery system, which is appropriate for commercialization. Current approaches used for preparation of gastro-retentive drug delivery system offers limited functional features to control the floating behavior. Recently, an extensive research has been developed to improve the gastric residence time by using nanofibers, which ultimately leads to the increased bioavailability of the drug. Multiple functional features and unique properties of nanofibers improve its gastro retention.

Conclusion: Nanofiber system provides stomach-specific drug release for longer duration; moreover, increased local action of the drug due to prolonged contact time with the gastric mucosa. Thus, the nanofiber system promises to be the potential approach for gastric retention drug delivery system.     

Massive hemoptysis: what place for medical and surgical treatment.

OBJECTIVE: The objective of the study was to define timing of surgical treatment in management of massive hemoptysis. METHODS: We performed a retrospective review of all patients admitted for massive hemoptysis in the intensive care unit of our thoracic surgery department. Treatment was managed according to the patient's status, the etiology of bleeding, the findings of bronchoscopy and computed tomographic scan. Therapeutic measures available were medical treatment, tracheal intubation (single or double lumen tube), interventional endoscopy, arterial embolisation and surgical treatment. RESULTS: Between September 1996 and December 2001, 43 patients were treated (nine females and 34 males with mean age of 54 years, range from 32 to 79). The mean red cell blood transfusion per patient was 1.57 Units. The patients were classified into three groups: Group 1, 11 patients were operated on immediately close to the bleeding crise (five pneumonectomy and six lobectomy); Group 2, five patients for whom operation was delayed from the 7th to the 22nd day after cessation of bleeding (five lobectomy); Group 3, 27 patients were treated by non-surgical methods (medical treatment, endobronchial treatment, percutaneous embolisation). Fifteen patients underwent an arterial embolization, which was complete in 13 cases. Among the five patients of group 2, cessation of bleeding was obtained by bronchial embolisation in four cases. Considering the whole series, 10 (23%) patients died: three (19%) patients in group 1, zero in group 2, seven (26%) in group 3. In two patients who were suffering from tumor necrosis, hemoptysis relapsed leading to death. CONCLUSION: Emergency thoracotomy for massive hemoptysis is at high risk. In case of bleeding from the arterial bronchial vessels, embolization may enable to postpone surgery and operate secondarily. In case of bleeding from the pulmonary vessels (tumor necrosis), surgical treatment must be immediate. An algorithm for management is proposed.