Thyme Oil-Containing Fluconazole-Loaded Transferosomal Bigel for Transdermal Delivery.

The objective of the present research was to develop fluconazole-loaded transferosomal bigels for transdermal delivery by employing statistical optimization (23 factorial design-based). Thin-film hydration was employed to prepare fluconazole-loaded transferomal suspensions, which were then incorporated into bigel system. A 23 factorial design was employed where ratios of lipids to edge activators, lipids (soya lecithin to cholesterol), and edge activators (sodium deoxycholate to Tween 80) were factors. Ex vivo permeation flux (Jss) of transferosomal bigels across porcine skin was analyzed as response. The optimal setting for optimized formulation (FO) was A= 4.96, B= 3.82, and C= 2.16. The optimized transferosomes showed 52.38 ± 1.76% DEE, 76.37 nm vesicle size, 0.233 PDI, - 20.3 mV zeta potential, and desirable deformability. TEM of optimized transferosomes exhibited a multilamelar structure. FO bigel's FE-SEM revealed a globule-shaped vesicular structure. Further, the optimized transferosomal suspension was incorporated into thyme oil (0.1% w/w)-containing bigel (TO-FO). Ex vivo transdermal fluconazole permeation from different transferosomal bigels was sustained over 24 h. The highest permeation flux (4.101 µg/cm2/h) was estimated for TO-FO bigel. TO-FO bigel presented 1.67-fold more increments of antifungal activity against Candida albicans than FO bigel. The prepared thyme oil (0.1% w/w)-containing transfersomal bigel formulations can be used as topical delivery system to treat candida related fungal infections.

Natural Polymeric Nanobiocomposites for Anti-Cancer Drug Delivery Therapeutics: A Recent Update.

Cancer is one of the most common lethal diseases and the leading cause of mortality worldwide. Effective cancer treatment is a global problem, and subsequent advancements in nanomedicine are useful as substitute management for anti-cancer agents. Nanotechnology, which is gaining popularity, enables fast-expanding delivery methods in science for curing diseases in a site-specific approach, utilizing natural bioactive substances because several studies have established that natural plant-based bioactive compounds can improve the effectiveness of chemotherapy. Bioactive, in combination with nanotechnology, is an exceptionally alluring and recent development in the fight against cancer. Along with their nutritional advantages, natural bioactive chemicals may be used as chemotherapeutic medications to manage cancer. Alginate, starch, xanthan gum, pectin, guar gum, hyaluronic acid, gelatin, albumin, collagen, cellulose, chitosan, and other biopolymers have been employed successfully in the delivery of medicinal products to particular sites. Due to their biodegradability, natural polymeric nanobiocomposites have garnered much interest in developing novel anti-cancer drug delivery methods. There are several techniques to create biopolymer-based nanoparticle systems. However, these systems must be created in an affordable and environmentally sustainable way to be more readily available, selective, and less hazardous to increase treatment effectiveness. Thus, an extensive comprehension of the various facets and recent developments in natural polymeric nanobiocomposites utilized to deliver anti-cancer drugs is imperative. The present article provides an overview of the latest research and developments in natural polymeric nanobiocomposites, particularly emphasizing their applications in the controlled and targeted delivery of anti-cancer drugs.

The role of bixin as antioxidant, anti-inflammatory, anticancer, and skin protecting natural product extracted from Bixa orellana L.

Since long, medicinal plants or herbs are being used in different traditional treatment systems as therapeutic agents to treat a variety of illnesses. Bixa orellana L., an medicinal plant (family: Bixaceae), is an Ayurvedic herb used to treat dyslipidemia, diarrhoea, and hepatitis since ancient times. B. orellana L., seeds contain an orange-red coloured component known as bixin (C25H30O4), which constitutes 80% of the extract.Chemically, bixin is a natural apocarotenoid, biosynthesized through the oxidative degradation of C40 carotenoids. Bixin helps to regulate the Nrf2/MyD88/TLR4 and TGF-1/PPAR-/Smad3 pathways, which further give it antifibrosis, antioxidant, and anti-inflammatory properties. This current review article presents a comprehensive review of bixin as an anti-inflammatory, antioxidant, anticancer,and skin protecting natural product. In addition, the biosynthesis and molecular target of bixin, along with bixin extraction techniques, are also presented.

RGD-decorated PLGA nanoparticles improved effectiveness and safety of cisplatin for lung cancer therapy.

Upon extensive pharmaceutical and biomedical research to treat lung cancer indicates that lung cancer remains one of the deadliest diseases and the leading cause of death in men and women worldwide. Lung cancer remains untreated and has a high mortality rate due to the limited potential for effective treatment with existing therapies. This highlights the urgent need to develop an effective, precise and sustainable solutions to treat lung cancer. In this study, we developed RGD receptor-targeted PLGA nanoparticles for the controlled and targeted co-delivery of cisplatin (CDDP) and upconversion nanoparticles (UCNP) in lung cancer therapy. Pluronic F127-RGD conjugate was synthesized by carbodiimide chemistry method and the conjugation was confirmed by FTIR and 1HNMR spectroscopy techniques. PLGA nanoparticles were developed by the double emulsification method, then the surface of the prepared nanoparticles was decorated with Pluronic F127-RGD conjugate. The prepared formulations were characterized for their particle size, polydispersity index, zeta potential, surface morphology, drug encapsulation efficiency, and in vitro drug release and haemolysis studies. Pharmacokinetic studies and safety parameters in BAL fluid were assessed in rats. Histopathology of rat lung tissue was performed. The obtained results of particle sizes of the nanoparticle formulations were found 100-200 nm, indicating the homogeneity of dispersed colloidal nanoparticles formulations. Transmission Electron Microscopy (TEM) revealed the spherical shape of the prepared nanoparticles. The drug encapsulation efficiency of PLGA nanoparticles was found to range from 60% to 80% with different nanoparticles counterparts. RGD receptor-targeted PLGA nanoparticles showed controlled drug release for up to 72 h. Further, RGD receptor-targeted PLGA nanoparticles achieved higher cytotoxicity in compared to CFT, CFT, and Ciszest-50 (marketed CDDP injection). The pharmacokinetic study revealed that RGD receptor-targeted PLGA nanoparticles were 4.6-fold more effective than Ciszest-50. Furthermore, RGD receptor-targeted PLGA nanoparticles exhibited negligible damage to lung tissue, low systemic toxicity, and high biocompatible and safety in lung tissue. The results of RGD receptor-targeted PLGA nanoparticles indicated that it is a promising anticancer system that could further exploited as a potent therapeutic approach for lung cancer.

Recent advances in erythrocyte membrane-camouflaged nanoparticles for the delivery of anti-cancer therapeutics.

INTRODUCTION: Red blood cell (or erythrocyte) membrane-camouflaged nanoparticles (RBC-NPs) not only have a superior circulation life and do not induce accelerated blood clearance but also possess special functions, which offers great potential in cancer therapy. AREAS COVERED: This review focuses on the recent advances of RBC-NPs for delivering various agents to treat cancers in light of their vital role in improving drug delivery. Meanwhile, the construction and in vivo behavior of RBC-NPs are discussed to provide an in-depth understanding of the basis of RBC-NPs for improved cancer drug delivery. EXPERT OPINION: Although RBC-NPs are quite prospective in delivering anti-cancer therapeutics, they are still in their infancy stage and many challenges need to be overcome for successful translation into the clinic. The preparation and modification of RBC membranes, the optimization of coating methods, the scale-up production and the quality control of RBC-NPs, and the drug loading and release should be carefully considered in the clinical translation of RBC-NPs for cancer therapy.

Design and evaluation of dental pastes Containing anti-inflammatory drugs

Abstract Periodontitis is an oral disease associated with inflammation and pain with swollen and bleeding gums. In the present study, dental pastes containing NSAIDs, namely, diclofenac sodium and nimesulide (1 % w/w) were prepared to treat periodontitis. Dental pastes of diclofenac sodium and nimesulide (1 % w/w) were prepared with/without mucoadhesive hydrocolloid polymers such as sodium carboxy methyl cellulose (NaCMC), hydroxyl ethyl cellulose (HEC) and methyl cellulose (MC) by conventional trituration method. The pH, drug content, viscosity, tube spreadability and tube extrudability of these prepared dental pastes were measured. These dental pastes of diclofenac sodium and nimesulide (1 % w/w) were characterized by FTIR analyses for drug-excipient compatibility. The in vitro drug releases from these dental pastes in 6.4 pH phosphate buffer solution displayed sustained release over longer period and the drug release rate was found to be decreased when the concentration of mucoadhesive polymer was increased. These dental pastes displayed good adhesion to the oral mucosa revealing more retention time in mouth when tested for ex vivo mucoadhesion using bovine cheek pouch. The stability study results reveal that the DC3 and NC3 dental paste formulations were found stable enough over a longer period in different storage conditions. The present study revealed that the prepared mucoadhesive dental pastes of diclofenac sodium and nimesulide (1 % w/w) had good adhesion with the oral mucosa to maintain consistent release of drugs over prolonged time.

Unraveling Variations in Celiac Trunk and Hepatic Artery by CT Angiography to Aid in Surgeries of Upper Abdominal Region.

Understanding of variations in the course and source of abdominal arteries is crucial for any surgical intervention in the peritoneal space. Intricate surgeries of the upper abdominal region, such as hepato-biliary, pancreatic, gastric and splenic surgeries, require precise knowledge of regular anatomy and different variations related to celiac trunk and hepatic artery. In addition, information about the origin of inferior phrenic artery is important in conditions such as hepatocellular carcinoma and gastroesophageal bleeding management. The present study gives an account of anatomical variations in origin and branching pattern of celiac trunk and hepatic artery by the use of CT (computed tomographic) angiography. The study was performed on 110 (66 females and 44 males) patients in a north Indian population. Results unraveled the most common celiac trunk variation as hepatosplenic trunk with left gastric artery, which was observed in 60% of cases, more common in females than in males. Gastrosplenic and hepato-gastric trunk could be seen in 4.55% and 1.82% cases respectively. Gastrosplenic trunk was more commonly found in females, whereas hepato-gastric trunk was more common in males. A gastrosplenic trunk, along with the hepato-mesenteric trunk, was observed in 1.82% cases and was more common in males. A celiacomesenteric trunk, in which the celiac trunk and superior mesenteric artery originated as a common trunk from the aorta, was seen only in 0.91% of cases, and exhibited an origin of right and left inferior phrenic artery from the left gastric artery. The most common variation of hepatic artery, in which the right hepatic artery was replaced and originated from the superior mesenteric artery, was observed in 3.64%, cases with a more common occurrence in males. In 1.82% cases, the left hepatic artery was replaced and originated from the left gastric artery, which was observed only in females. Common hepatic artery originated from the superior mesenteric artery, as observed in 1.82% cases, with slightly higher occurrence in males. These findings not only add to the existing knowledge apart from giving an overview of variations in north Indian population, but also give an account of their correlation with gender. The present study will prove to be important for various surgeries of the upper abdominal region.

Molecular insights and novel approaches for targeting tumor metastasis.

In recent years, due to the effective drug delivery and preciseness of tumor sites or microenvironment, the targeted drug delivery approaches have gained ample attention for tumor metastasis therapy. The conventional treatment approaches for metastasis therapy have reported with immense adverse effects because they exhibited maximum probability of killing the carcinogenic cells along with healthy cells. The tumor vasculature, comprising of vasculogenic impressions and angiogenesis, greatly depends upon the growth and metastasis in the tumors. Therefore, various nanocarriers-based delivery approaches for targeting to tumor vasculature have been attempted as efficient and potential approaches for the treatment of tumor metastasis and the associated lesions. Furthermore, the targeted drug delivery approaches have found to be most apt way to overcome from all the limitations and adverse effects associated with the conventional therapies. In this review, various approaches for efficient targeting of pharmacologically active chemotherapeutics against tumor metastasis with the cohesive objectives of prognosis, tracking and therapy are summarized.

Carbon Nanotubes: An Emerging Drug Delivery Carrier in Cancer Therapeutics.

BACKGROUND: The scope of nanotechnology has been extended to almost every sphere of our daily life. As a result of this, nanocarriers like Carbon Nanotubes (CNTs) are gaining considerable attention for their use in various therapeutic and diagnostic applications. OBJECTIVE: The objective of the current article is to review various important features of CNTs that make them as efficient carriers for anticancer drug delivery in cancer therapeutics. METHODS: In this review article, different works of literature are reported on various prospective applications of CNTs in the targeting of multiple kinds of cancerous cells of different organs via; the loading of various anticancer agents. RESULTS: Actually, CNTs are the 3rd allotropic type of the carbon-fullerenes that are a part of the cylindrical tubular architecture. CNTs possess some excellent physicochemical characteristics and unique structural features that provide an effective platform to deliver anticancer drugs to target specific sites for achieving a high level of therapeutic effectiveness even in cancer therapeutics. For better results, CNTs are functionalized and modified with different classes of therapeutically bioactive molecules via; the formation of stable covalent bonding or by the use of supramolecular assemblies based on the noncovalent interaction(s). In recent years, the applications of CNTs for the delivery of various kinds of anticancer drugs and targeting of tumor sites have been reported by various research groups. CONCLUSION: CNTs represent an emerging nanocarrier material for the delivery and targeting of numerous anticancer drugs in cancer therapeutics.

Alginate gel-coated oil-entrapped alginate-tamarind gum-magnesium stearate buoyant beads of risperidone.

A novel alginate gel-coated oil-entrapped calcium-alginate-tamarind gum (TG)-magnesium stearate (MS) composite floating beads was developed for intragastric risperidone delivery with a view to improving its oral bioavailability. The TG-blended alginate core beads containing olive oil and MS as low-density materials were accomplished by ionotropic gelation technique. Effects of polymer-blend ratio (sodium alginate:TG) and crosslinker (CaCl2) concentration on drug entrapment efficiency (DEE, %) and cumulative drug release after 8 h (Q8h, %) were studied to optimize the core beads by a 3(2) factorial design. The optimized beads (F-O) exhibited DEE of 75.19±0.75% and Q8h of 78.04±0.38% with minimum errors in prediction. The alginate gel-coated optimized beads displayed superior buoyancy and sustained drug release property. The drug release profiles of the drug-loaded uncoated and coated beads were best fitted in Higuchi kinetic model with Fickian and anomalous diffusion driven mechanisms, respectively. The optimized beads yielded a notable sustained drug release profile as compared to marketed immediate release preparation. The uncoated and coated Ca-alginate-TG-MS beads were also characterized by SEM, FTIR and P-XRD analyses. Thus, the newly developed alginate-gel coated oil-entrapped alginate-TG-MS composite beads are suitable for intragastric delivery of risperidone over a prolonged period of time.

Alginate-sterculia gum gel-coated oil-entrapped alginate beads for gastroretentive risperidone delivery.

Novel floating-mucoadhesive oil-entrapped alginate beads coated with crossslinked alginate-sterculia gum gel membrane was developed for gastroretentive risperidone delivery. Oil-entrapped alginate beads containing risperidone as core were prepared by ionotropic gelation technique. Effects of polymer to drug ratio and oil to water ratio on drug entrapment efficiency (%) and cumulative drug release after 8h (%) were studied to optimize the core beads by a 3(2) factorial design. The optimized beads (F-O) demonstrated drug entrapment efficiency of 83.73±0.81% and cumulative drug release of 70.84±0.27% after 8h. The biopolymeric-coated optimized beads exhibited excellent buoyancy, better ex vivo mucoadhesion and slower drug release rate. The drug release profiles of risperidone-loaded uncoated and coated beads were best fitted in Korsmeyer-Peppas model with Fickian diffusion mechanism. The beads were also examined for the drug-excipients compatibility, drug crystallinity and surface morphology by FTIR, P-XRD and SEM analyses, respectively.

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.

Oil-entrapped sterculia gum-alginate buoyant systems of aceclofenac: development and in vitro evaluation.

The current investigation deals with the development and optimization of oil-entrapped sterculia gum-alginate buoyant beads containing aceclofenac by ionotropic emulsion-gelation technique using 3(2) factorial design. The effect of polymer to drug ratio and sodium alginate to sterculia gum ratio on the drug entrapment efficiency (%), and cumulative drug release after 7 h (%) was optimized. The optimized oil-entrapped sterculia gum-alginate buoyant beads containing aceclofenac (F-O) showed drug entrapment efficiency of 90.92±2.34%, cumulative drug release of 41.65±3.97% after 7 h in simulated gastric fluid (pH 1.2), and well buoyancy over 8 h in simulated gastric fluid (pH 1.2) with 5.20 min buoyant lag-time. The in vitro drug release from these buoyant beads followed Korsmeyer-Peppas model (R(2)=0.9866-0.9995) with anomalous (non-Fickian) diffusion drug release mechanism. These new sterculia gum-alginate buoyant beads containing aceclofenac were also characterized using SEM, FTIR, and P-XRD analysis.

Antimicrobial activity assessment of time-dependent release bilayer tablets of amoxicillin trihydrate

The aim of present study was the assessment of antimicrobial activity of prepared time-dependent release bilayer tablets of amoxicillin trihydrate and in vitro evaluation of drug release by antimicrobial assay using agar plate diffusion method. The bilayer tablets comprised of a delayed and sustained release layer. Direct compression method was used for the preparation of bilayer tablets containing Eudragit-L100 D55 as delayed release polymer, and HPMCK4M and HPMCK15 as sustained release polymers. The prepared bilayer tablets containing amoxicillin trihydrate were evaluated for hardness, thickness, friability, weight variation and drug content. Further, in vitro drug release was assessed by antimicrobial assay using S. aureus and E. coli as test microorganisms. The aliquot samples of in vitro drug release study were found to be effective against both microorganisms for 16 hours due to sustained action. The in vitro drug release study and antimicrobial assay showed that bilayer tablets have sustained release profile of drug delivery with time-dependent burst release after a lag-time of 2 hours. The lower MIC value (2 µg/mL) of prepared bilayer tablets vis-à-vis marketed preparation (5 µg/mL) represented its good antimicrobial activity.

O objetivo do presente estudo foi avaliar a atividade antimicrobiana de formulações de comprimidos de dupla camada contendo amoxicilina triidratada para liberação tempo dependente e avaliação da liberação in vitro do fármaco pelo ensaio de atividade antimicrobiana utilizando o método de difusão em placa de ágar. Os comprimidos de dupla camada consistem em uma camada para liberação retardada e outra sustentada. O método de compressão direta foi usado para a preparação dos comprimidos de dupla camada contendo Eudragit-L 100 D55 como polímero para liberação retardada e HPMCK4M ou HPMCK15 como polímeros para liberação sustentada. As formulações de comprimidos de dupla camada contendo amoxicilina triidratada foram avaliadas quanto a dureza, espessura, friabilidade, variação de peso e conteúdo de fármaco. Além disso, a liberação do fármaco in vitro foi avaliada por ensaio de atividade antimicrobiana usando S. aureus e E. coli como microrganismos teste. A alíquota das amostras do estudo de liberação do fármaco in vitro demonstrou ser efetiva contra ambos os microrganismos por um período de 16 horas devido à ação sustentada. O estudo de liberação do fármaco in vitro e o ensaio de atividade antimicrobiana mostraram que os comprimidos de dupla camada tiveram um perfil de liberação sustentada do fármaco com um pico de liberação após 2 horas de ensaio. O menor valor de MIC (2 ug/mL) dos comprimidos de dupla camada quando comparados à formulação comercial (5 ug/mL) representa uma boa atividade antimicrobiana.