Guest-host Relationship of Cyclodextrin and its Pharmacological Benefits.

Many methods, including solid dispersion, micellization, and inclusion complexes, have been employed to increase the solubility of potent drugs. Beta-cyclodextrin (ßCD) is a cyclic oligosaccharide consisting of seven glucopyranoside molecules, and is a widely used polymer for formulating soluble inclusion complexes of hydrophobic drugs. The enzymatic activity of Glycosyltransferase or α-amylase converts starch or its derivatives into a mixture of cyclodextrins. The ßCD units are characterized by α -(1-4) glucopyranose bonds. Cyclodextrins possess certain properties that make them very distinctive because of their toroidal or truncated cage-like supramolecular configurations with multiple hydroxyl groups at each end. This allowed them to encapsulate hydrophobic compounds by forming inclusion complexes without losing their solubility in water. Chemical modifications and newer derivatives, such as methylated ßCD, more soluble hydroxyl propyl methyl ßCD, and sodium salts of sulfobutylether-ßCD, known as dexolve® or captisol®, have envisaged the use of CDs in various pharmaceutical, medical, and cosmetic industries. The successful inclusion of drug complexes has demonstrated improved solubility, bioavailability, drug resistance reduction, targeting, and penetration across skin and brain tissues. This review encompasses the current applications of ß-CDs in improving the disease outcomes of antimicrobials and antifungals as well as anticancer and anti-tubercular drugs.

Nanoencapsulation of Polyphenols as Drugs and Supplements for Enhancing Therapeutic Profile - A Review.

Polyphenolic phytoconstituents have been widely in use worldwide for ages and are categorised as secondary metabolites of plants. The application of polyphenols such as quercetin, resveratrol, curcumin as nutritional supplements has been researched widely. The use of polyphenols and specifically quercetin, for improving memory and mental endurance has shown significant effects among rats. Even though similar results have not been resonated among humans, but preclinical results have encouraged researchers to explore other polyphenols to study the effects as supplements among athletes. The phytopharmacological research has elucidated the use of natural polyphenols to prevent and treat various physiological and metabolic disorders owing to their free radical scavenging properties, anti-inflammatory, anti-cancer, and immunomodulatory effects. In- -spite of the tremendous pharmacological profile, one of the most dominant problem regarding the use of polyphenolic compounds is their low bioavailability. Nanonization is considered as one of the most prominent approaches among many. This article aims to review and discuss the molecular mechanisms of recently developed nanocarrier-based drug delivery systems for polyphenols and their application as drugs and supplements. Nanoformulations of natural polyphenols as bioactive agents, such as quercetin, kaempferol, fisetin, rutin, hesperetin, and naringenin epigalloccatechin- 3-gallate, genistein, ellagic acid, gallic acid, chlorogenic acid, ferulic acid, curcuminoids, and stilbenes is expected to have better efficacy. These delivery systems are expected to provide higher penetrability of polyphenols at cellular levels and exhibit a controlled release of the drugs. It is widely accepted that natural polyphenols do demonstrate significant therapeutic effects. However, the hindrances in their absorption, specificity, and bioavailability can be overcome using nanotechnology.

Nanotechnological Advances in the Treatment of Epilepsy.

Epilepsy is known as one of the major challenges for medical science. The sudden appearance of a seizure has been a significant health emergency as it may lead to further complications. Although key advancements have been achieved in terms of pharmacological approaches for epilepsy, many issues remain uncertain. Lipid carriers have been at the forefront, especially in neurodegenerative diseases, such as epilepsy, Alzheimer's, dementia, etc. The blood-brain barrier still appears to be a major impediment in the successful treatment of epileptic seizures. This is mainly due to the limited bioavailability of most anti-convulsant drugs. The present review encompasses the issues underlying the current approach for epilepsy drug treatment and highlights the newer, novel, and more precise drug delivery system to manage seizures. The advantage of using a lipidbased delivery system is its superior absorption in the brain cells. Ample evidence shows that reducing the particle size also infuses the drug easily through the blood-brain barrier. The application of liposomes, polymeric nanoparticles, metallic nanoparticles, and solid lipid nanoparticles for the treatment and management of epilepsy has been highlighted in the present review. This review provides an overview of the current status of the treatment and recent advances in the treatment of epilepsy.

Knowledge, attitude, perception of Muslim parents towards vaccination in Malaysia.

Malaysia is a predominant Muslim country and the recent surge in vaccine-preventable disease enticed us to conduct a survey to measure the Knowledge, Attitude and Perception of Muslim parents toward vaccination process. The data were collected under four segments such as demography, Knowledge, Attitude and Perception. The questionnaire had high internal consistency (0.823) for Cronbach's alpha. The sociodemographic determinants such as marital status (OR = 1.12; 0.91-1.38;p < .05), education level (college OR = 1.35; 1.12-1.64;p < .05, secondary OR = 1.22; 1.01-1.47;p < .05) and the occupation of parents (OR = 1.25; 1.07-1.45;p < .05) were observed affecting the Knowledge score significantly. Majority of Malaysian Muslim parents believed that "vaccine is not prohibited in Islam" and most of them also rejected the belief that "all vaccines are non halal and hence should be avoided". None of the sociodemographic determinants significantly affected the Attitude and Perception score of the Muslim parents. It was observed that the Attitude and Perception score did not establish any association with any of the socio-demographic determinants and hence the null hypothesis that Malaysian Muslim parents had positive Attitude and good Perception toward vaccination process was accepted.

Lipid-based Nanocarriers for Cancer and Tumor Treatment.

Cancer and tumor have been major reasons for numerous deaths in this century across the world. Many strategies have been designed to treat, diagnose, or prevent cancer. The success of chemotherapy largely depends on drug targeting. The advent of nanotechnology has vastly improved drug delivery for targeting and diagnosis. Nevertheless, the accuracy of drug targeting with polymeric nanoparticles has always been questionable. The polymeric nanoparticles synthesized from varieties of lipid-based compounds or combined with vectors, such as liposomes, ethosomes, and transfersomes, may allow the drug to overcome the issue of resistance to drug absorption in biological membranes. The combined effects of lipid-based nanocarriers are known to improve the efficacy and accuracy of polymeric nanoparticles. The present review explores the application of lipid based nanocarriers in the treatment and diagnosis of cancer A special focus is given to the use of lipid-based nanocarriers in the treatment, diagnosis, and mitigation of cancer located in blood, brain, lung, and colon. The treatment of these cancers has always been questionable as the chances of relapse are very high. The review encompasses the use of lipid-based nanocarriers in targeting tissue-specific cancer cells.

Purple heart plant leaves extract-mediated silver nanoparticle synthesis: Optimization by Box-Behnken design.

The present research work describes a novel method for green synthesis of silver nanoparticles using purple heart plant leaves extract, which is recognized as frequently found in households as an ornamental plant. The aqueous methanolic extract of purple heart plant leaves was prepared and employed in the synthesis of stable silver nanoparticles via biological reduction method. The purple heart plant leaves extract-mediated synthesized silver nanoparticles were systematically optimized using Box-Behnken design considering the effect of various independent variables (factors) like concentration of AgNO3, temperature and volume of purple heart plant leaves extract solution on the responses like particle size and polydispersity index of synthesized silver nanoparticles were optimized. Mathematical modelling was performed using quadratic polynomial model and response surface analysis was done to understand the factor-response relationship. The synthesized silver nanoparticles at optimum condition were found to be of spherical in shape under TEM with particle size of 98 nm and polydispersity index of 0.15. Optimized silver nanoparticles were further characterized through UV-VIS spectrophotometry, FTIR spectroscopy and TEM imaging studies. Also, the silver nanoparticles were evaluated for antibacterial activity on E. coli and S. aureus. In a nutshell, the studies construed successful synthesis of silver nanoparticles along with thorough understanding of the associated factors influencing their quality characteristics and significantly improved antibacterial activity as beneficial effect.

Extraction and characterization of cashew tree (Anacardium occidentale) gum; use in aceclofenac dental pastes.

In the current work, the usefulness of extracted cashew tree gum (CG) as pharmaceutical excipient in dental pastes containing aceclofenac (AC) for the pain management in the periodontitis treatment was investigated. CG was extracted from crude exudate of cashew tree (Anacardium occidentale, family: Anacardiaceae) (yield 19.22%). Physicochemical characteristics like colour, odour, taste, solubility, pH and viscosity of extracted CG were estimated; the phytochemical identification tests indicated the presence of carbohydrates and mucilage within it. It was also characterized by FTIR spectroscopy and 1H NMR analyses. Using the extracted CG (as natural mucoadhesive polymer) with calcium carbonate (abrasive agent), glycerin (humectant and cosolvent), methyl paraben (preservative), sodium lauryl sulfate (surfactant) and camphor (flavoring agent), 1% w/w AC dental pastes was formulated via conventional trituration. The drug contents, viscosities and pHs, tube extrudabilities and tube spreadabilities of these dental pastes were observed within permissible ranges. The dental pastes demonstrated sustained AC releasing over 6 h, in vitro and also revealed good adhesion to the oral mucosal membrane. These 1% w/w AC dental pastes can be used in the effectual management of dental inflammation and pain through local delivery of AC over a prolonged in the periodontitis treatment.

QbD-Driven Development and Validation of Liquid Chromatography Tandem Mass Spectrometric Method for the Quantitation of Sildenafil in Human Plasma.

The present work was employing the Quality by Design approach for the development and validation of a LC-MS-MS method to support the clinical advancement in determination of sildenafil in human plasma using lorazepam as an internal standard. Sample preparation involved solid phase extraction and calibration range observed between 3 and 1,700 ng/mL. The method was systematically optimized by employing Box-Behnken design and used mobile phase flow rate, pH and composition of mobile phase as the critical factors, and assessing the design for retention time and peak area as the responses. A substantial decrease in the variability associated with the method variables was shown in optimization studies and confirmed enhanced method robustness. The present studies revealed that developed method achieves all the regulatory requirements for linearity, accuracy, precision, selectivity, sensitivity and stability for the determination of sildenafil in human plasma. There was not any significant change in the stability of the drug shown by stability studies, performed in human plasma through freeze-thaw cycles, bench-top stability, short-term stability, long-term stability and auto sampler stability. In short, this method shows satisfactory results for the analysis of sildenafil in human plasma and possesses high degree of utility in pharmacokinetic and bioequivalence studies.

Alginate-based bipolymeric-nanobioceramic composite matrices for sustained drug release.

Alginate-based bipolymeric-nanobioceramic composite matrices for sustained drug release were developed through incorporation of nano-hydroxyapatite [nHAp] powders within ionotropically-gelled calcium ion-induced alginate-poly (vinyl pyrrolidone) blends polymeric systems. nHAp powders were synthesized by precipitation technique using calcium hydroxide [Ca(OH)2] and orthophosphoric acid [H3PO4] as raw materials. The average particle size of these was synthesized. nHAp powders was found as 19.04 nm and used to prepare nHAp-alginate-PVP beads containing DS. These beads exhibited drug entrapment efficiency (%) of 65.82±1.88 to 94.45±3.72% and average bead sizes of 0.98±0.07 to 1.23±0.15 mm. These beads were characterized by scanning electron microscopy (SEM) and Fourier transform-infra red (FTIR) spectroscopy analyses. Various nHAp-alginate-PVP beads containing DS exhibited prolonged sustained drug release and followed the Koresmeyer-Peppas model of drug release (R2=0.9908-0.9978) with non-Fickian release (anomalous transport) mechanism (n=0.73-0.84) for drug release over 8 h.

Alginate-okra gum blend beads of diclofenac sodium from aqueous template using ZnSO4 as a cross-linker.

Zinc (Zn(2+))-ion induced diclofenac sodium (DS)-loaded alginate-okra (Hibiscus esculentus) gum (OG) blend beads was successfully formulated through Zn(2+)-ion induced ionic-gelation cross-linking method in a complete aqueous environment. Effects of polymer-blend ratio and cross-linker concentration on drug encapsulation efficiency (DEE) and cumulative drug release at 8 h (R8h) were optimized by 3(2)-factorial design. The optimized formulation of Zn(2+)-ion induced DS-loaded alginate-OG beads demonstrated 89.27±3.58% of DEE and 43.73±2.83% of R8h. The bead sizes were within 1.10±0.07 to 1.38±0.14 mm. The bead surface morphology was analyzed by SEM. The drug-polymer interaction in the optimized bead matrix was analyzed by FTIR and P-XRD. These beads exhibited sustained in vitro drug release over a prolonged period of 8h and followed controlled-release (zero-order) pattern with super case-II transport mechanism. The swelling and degradation of the optimized beads was influenced by the pH of test mediums, which might be suitable for intestinal drug delivery.

Optimization of aceclofenac-loaded pectinate-poly(vinyl pyrrolidone) beads by response surface methodology.

The paper describes development of aceclofenac-loaded pectinate-poly(vinyl pyrrolidone) [PVP] beads through ionotropic-gelation. Effects of amount of pectin and PVP on drug encapsulation efficiency (DEE), and cumulative drug release at 6h (R6h) were optimized by using response surface methodology. The optimized beads showed DEE of 96.58 ± 4.15% and R6h of 41.62 ± 2.18% with controlled drug release pattern. FTIR spectroscopy analysis revealed possible intermolecular hydrogen bonding, which could be formed between C=O groups of PVP and -OH groups of pectin in these beads. The swelling of these beads were influenced by pH of the medium.

Development and validation of an improved LC-MS/MS method for the quantification of desloratadine and its metabolite in human plasma using deutrated desloratadine as internal standard.

PURPOSE: For the determination of desloratadine (DES) and 3-OH desloratadine (3-OHD) in human plasma using deutrated desloratadine (DESD5) as internal standard (IS), a novel stability indicating liquid chromatography-tandem mass spectrometric method was developed and validated to support the clinical advancement. MATERIALS AND METHODS: The solid-phase extraction method used for sample preparation and calibration range was 100-11,000 pg/ml, for which a quadratic regression (1/x(2)) was best fitted. The blank plasma was screened and observed free from any endogenous interference. RESULTS: The accuracy (% nominal) at low limit of quantification LLOQ level for DES and 3-OHD was 100.4% and 99.9% whereas precision (%CV) was 4.6 and 5.1%. They (DES and 3-OHD) were stable in human plasma after five freeze-thaw cycles, at room temperature for 23.8 hour, bench top stability for 6.4 hour. CONCLUSION: This method fulfills all the regulatory requirements for selectivity, sensitivity, precision, accuracy, stability, goodness of fit, and ruggedness of the method for the determination of DES and 3-OHD in human plasma.

Development and validation of LC-MS/MS method for the quantitation of lenalidomide in human plasma using Box-Behnken experimental design.

For the determination of lenalidomide using carbamazepine as an internal standard, an ultra-fast stability indicating LC-MS/MS method was developed, validated and optimized to support clinical advancement. The samples were prepared by solid-phase extraction. The calibration range was 2-1000 ng mL(-1), for which a quadratic regression (1/x(2)) was best fitted. The method was validated and a 3(2) factorial was employed using Box-Behnken experimental design for the validation of robustness. These designs have three factors such as mobile phase composition (X(1)), flow rate (X(2)) and pH (X(3)) while peak area (Y(1)) and retention time (Y(2)) were taken as response. This showed that little changes in mobile phase and flow rate affect the response while pH has no affect. Lenalidomide and carbamazepine were stable in human plasma after five freeze thaw cycles, at room temperature for 23.7 h, bench top stability for 6.4 h. This method competes with all the regulatory requirements for selectivity, sensitivity, precision, accuracy, and stability for the determination of lenalidomide in human plasma, as well as being highly sensitive and effective for the pharmacokinetic and bioequivalence study of lenalidomide.

Development and optimization of hydroxyapatite-ofloxacin implants for possible bone delivery in osteomyelitis treatment.

The present study deals with preparation, optimization and in-vitro drug release study of hydroxyapatite (HAp)- ofloxacin for bone-implantable delivery in osteomyelitis treatment. The effect of drug amount added, and orthophosphoric acid addition rate as process parameters on the drug loading into HAp-system by precipitation method was optimized by using 32 factorial design. The response surface methodology utilizing polynomial equation was used to search for optimal drug loading into HAp-system. The responses observed coincided well with the predicted values obtained through optimization technique. HAp-ofloxacin bone-implants were manufactured using synthesized HAp-ofloxacin composite powders and 2 % w/v aqueous solution of sodium alginate was used as binder. Characterization of the delivery system was done by FTIR spectroscopy. The in-vitro ofloxacin release from optimized HAp-ofloxacin bone-implants was slow and sustained over 10 weeks. The drug release pattern was correlated well with Korsmeyer-Peppas model and was followed by Fickian (diffusional) release mechanism.

Fenugreek seed mucilage-alginate mucoadhesive beads of metformin HCl: Design, optimization and evaluation.

The work investigates the development and optimization of fenugreek (Trigonella foenum-graecum L.) seed mucilage (FSM)-alginate mucoadhesive beads containing metformin HCl through ionotropic gelation using 3(2) factorial design. The effect of polymer-blend ratio (sodium alginate to FSM) and cross-linker (CaCl(2)) concentration on the drug encapsulation efficiency (DEE, %), and cumulative drug release after 10h (R(10h), %) was optimized. The DEE (%) of all these beads was within the range of 71.63 ± 2.32 to 95.08 ± 3.73% with sustained in vitro drug release of 69.78 ± 2.43% to 95.70 ± 4.26% over 10h. The in vitro drug release from these beads was followed controlled-release (zero-order) pattern (R(2)=0.9910 to 0.9953) with super case-II transport mechanism. The average size of these beads was within the range of 0.92 ± 0.05 to 1.30 ± 0.14 mm. The beads were also characterized by SEM, FTIR and (1)H NMR. The swelling and degradation of FSM-alginate beads containing metformin HCl were influenced by pH of the test medium. These beads also exhibited good mucoadhesivity in wash-off test. The optimized FSM-alginate mucoadhesive beads containing metformin HCl showed significant hypoglycemic effect in alloxan-induced diabetic rats over prolonged period after oral administration.

Advancement in carbon nanotubes: basics, biomedical applications and toxicity.

OBJECTIVES: Carbon nanotubes (CNTs) have attracted much attention by researchers worldwide in recent years for their small dimensions and unique architecture, and for having immense potential in nanomedicine as biocompatible and supportive substrates, as a novel tool for the delivery of therapeutic molecules including peptides, RNA and DNA, and also as sensors, actuators and composites. KEY FINDINGS: CNTs have been employed in the development of molecular electronic, composite materials and others due to their unique atomic structure, high surface area-to-volume ratio and excellent electronic, mechanical and thermal properties. Recently they have been exploited as novel nanocarriers in drug delivery systems and biomedical applications. Their larger inner volume as compared with the dimensions of the tube and easy immobilization of their outer surface with biocompatible materials make CNTs a superior nanomaterial for drug delivery. Literature reveals that CNTs are versatile carriers for controlled and targeted drug delivery, especially for cancer cells, because of their cell membrane penetrability. SUMMARY: This review enlightens the biomedical application of CNTs with special emphasis on utilization in controlled and targeted drug delivery, as a diagnostics tool and other possible uses in therapeutic systems. The review also focuses on the toxicity aspects of CNTs, and revealed that genotoxic potential, mutagenic and carcinogenic effects of different types of CNTs must be explored and overcome by formulating safe biomaterial for drug delivery. The review also describes the regulatory aspects and clinical and market status of CNTs.