Development and characterization of lung surfactant-coated polymer nanoparticles for pulmonary drug delivery.

Lung cancer is often diagnosed at an advanced stage where tumors are usually inoperable and first-line therapies are inefficient and have off-targeted adverse effects, resulting in poor patient survival. Here, we report the development of an inhalable poly lactic-co-glycolic acid polymer-based nanoparticle (PLGA-NP) formulation with a biomimetic Infasurf® lung surfactant (LS) coating, for localized and sustained lung cancer drug delivery. The nanoparticles (188 ± 7 nm) were stable in phosphate buffered saline, serum and Gamble's solution (simulated lung fluid), and demonstrated cytocompatibility up to 1000 µg/mL concentration and dose-dependent uptake by lung cancer cells. The LS coating significantly decreased nanoparticle (NP) uptake by NR8383 alveolar macrophages in vitro compared to uncoated NPs. The coating, however, did not impair NP uptake by A549 lung adenocarcinoma cells. The anti-cancer drug gemcitabine hydrochloride encapsulated in the PLGA core was released in a sustained manner while the paclitaxel loaded in the LS shell demonstrated a rapid or burst release profile over 21 days. The drug-loaded NPs significantly decreased cancer cell survival and colony formation in vitro compared to free drugs and single drug-loaded NPs. In vivo studies confirmed greater retention of LS-coated NPs in the lungs of C57BL/6 WT mice compared to uncoated NPs, at 24 h and 72 h following intranasal administration. The overall results confirm that LS coating is a unique strategy for cloaking polymeric NPs to potentially prevent their rapid lung clearance and facilitate prolonged pulmonary drug delivery.

Fabrication of PNIPAm-based thermoresponsive hydrogel microwell arrays for tumor spheroid formation.

Complex three-dimensional (3D) cell cultures are being increasingly implemented in biomedical research as they provide important insights into complex cancer biology, and cell-cell and cell-matrix interactions in the tumor microenvironment. However, most methods used today for 3D cell culture are limited by high cost, the need for specialized skills, low throughput and the use of unnatural culture environments. We report the development of a unique biomimetic hydrogel microwell array platform for the generation and stress-free isolation of cancer spheroids. The poly N-isopropylacrylamide-based hydrogel microwell array (PHMA) has thermoresponsive properties allowing for the attachment and growth of cell aggregates/ spheroids at 37 °C, and their easy isolation at room temperature (RT). The reversible phase transition of the microwell arrays at 35 °C was confirmed visually and by differential scanning calorimetry. Swelling/ shrinking studies and EVOS imaging established that the microwell arrays are hydrophilic and swollen at temperatures <35 °C, while they shrink and are hydrophobic at temperatures >35 °C. Spheroid development within the PHMA was optimized for seeding density, incubation time and cell viability. Spheroids of A549, HeLa and MG-63 cancer cell lines, and human lung fibroblast (HLF) cell line generated within the PHMAs had relatively spherical morphology with hypoxic cores. Finally, using MG-63 cell spheroids as representative models, a proof-of-concept drug response study using doxorubicin hydrochloride was conducted. Overall, we demonstrate that the PHMAs are an innovative alternative to currently used 3D cell culture techniques, for the high-throughput generation of cell spheroids for disease modeling and drug screening applications.

Emerging drug delivery strategies for idiopathic pulmonary fibrosis treatment.

Idiopathic pulmonary fibrosis (IPF) is a debilitating and fatal condition that causes severe scarring of the lungs. While the pathogenesis of IPF continues to be extensively studied and several factors have been considered, an exact cause has yet to be established. With inadequate treatment options and no cure available, overall disease prognosis is still poor. Existing oral therapies, pirfenidone and nintedanib, may attempt to improve the patients' quality of life by mitigating symptoms and slowing disease progression, however chronic doses and systemic deliveries of these drugs can lead to severe side effects. The lack of effective treatment options calls for further investigation of restorative as well as additional palliative therapies for IPF. Nanoparticle-based sustained drug delivery strategies can be utilized to ensure targeted delivery for site-specific treatment as well as long-acting therapy, improving overall patient compliance. This review provides an update on promising strategies for the delivery of anti-fibrotic agents, along with an overview of key therapeutic targets as well as relevant emerging therapies currently being evaluated for IPF treatment.

Porous Polymeric Microspheres With Controllable Pore Diameters for Tissue Engineered Lung Tumor Model Development.

Complex cell cultures are more representative of in vivo conditions than conventionally used monolayer cultures, and are hence being investigated for predictive screening of therapeutic agents. Poly lactide co-glycolide (PLGA) polymer is frequently used in the development of porous substrates for complex cell culture. Substrates or scaffolds with highly interconnected, micrometric pores have been shown to positively impact tissue model formation by enhancing cell attachment and infiltration. We report a novel alginate microsphere (AMS)-based controlled pore formation method for the development of porous, biodegradable PLGA microspheres (PPMS), for tissue engineered lung tumor model development. The AMS porogen, non-porous PLGA microspheres (PLGAMS) and PPMS had spherical morphology (mean diameters: 10.3 ± 4, 79 ± 21.8, and 103 ± 30 µm, respectively). The PPMS had relatively uniform pores and a porosity of 45.5%. Degradation studies show that PPMS effectively maintained their structural integrity with time whereas PLGAMS showed shrunken morphology. The optimized cell seeding density on PPMS was 25 × 103 cells/mg of particles/well. Collagen coating on PPMS significantly enhanced the attachment and proliferation of co-cultures of A549 lung adenocarcinoma and MRC-5 lung fibroblast cells. Preliminary proof-of-concept drug screening studies using mono- and combination anti-cancer therapies demonstrated that the tissue-engineered lung tumor model had a significantly higher resistance to the tested drugs than the monolayer co-cultures. These studies indicate that the PPMS with controllable pore diameters may be a suitable platform for the development of complex tumor cultures for early in vitro drug screening applications.

Ultrasound-Enhanced Chemiluminescence for Bioimaging.

Tissue imaging has emerged as an important aspect of theragnosis. It is essential not only to evaluate the degree of the disease and thus provide appropriate treatments, but also to monitor the delivery of administered drugs and the subsequent recovery of target tissues. Several techniques including magnetic resonance imaging (MRI), computational tomography (CT), acoustic tomography (AT), biofluorescence (BF) and chemiluminescence (CL), have been developed to reconstruct three-dimensional images of tissues. While imaging has been achieved with adequate spatial resolution for shallow depths, challenges still remain for imaging deep tissues. Energy loss is usually observed when using a magnetic field or traditional ultrasound (US), which leads to a need for more powerful energy input. This may subsequently result in tissue damage. CT requires exposure to radiation and a high dose of contrast agent to be administered for imaging. The BF technique, meanwhile, is affected by strong scattering of light and autofluorescence of tissues. The CL is a more selective and sensitive method as stable luminophores are produced from physiochemical reactions, e.g. with reactive oxygen species. Development of near infrared-emitting luminophores also bring potential for application of CL in deep tissues and whole animal studies. However, traditional CL imaging requires an enhancer to increase the intensity of low-level light emissions, while reducing the scattering of emitted light through turbid tissue environment. There has been interest in the use of focused ultrasound (FUS), which can allow acoustic waves to propagate within tissues and modulate chemiluminescence signals. While light scattering is decreased, the spatial resolution is increased with the assistance of US. In this review, chemiluminescence detection in deep tissues with assistance of FUS will be highlighted to discuss its potential in deep tissue imaging.

Pharmacokinetic and Pharmacodynamic Evaluation of Resveratrol Loaded Cationic Liposomes for Targeting Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. The destructive nature of the disease makes it difficult for clinicians to manage the condition. Hence, there is an urgent need to find new alternatives for HCC, as the role of conventional cytotoxic drugs has reached a plateau to control HCC associated mortality. Antioxidant compounds of plant origin with potential anti-tumor effect have been recognized as alternate modes in cancer treatment and chemoprevention. Resveratrol (RS) is a model natural nonflavonoid drug known for its anti-cancer activity. However, its clinical application is limited due to its poor bioavailability. The current research work aims to formulate, optimize, and characterize RS loaded cationic liposomes (RLs) for specific delivery in HCC. The optimized liposomes formulation (RL5) was spherical with a vesicle size (VS) of 145.78 ± 9.9 nm, ζ potential (ZP) of 38.03 ± 9.12 mV, and encapsulation efficiency (EE) of 78.14 ± 8.04%. In vitro cytotoxicity studies in HepG2 cells demonstrated an improved anti-cancer activity of RL5 in comparison with free RS. These outcomes were supported by a cell uptake study in HepG2 cells, in which RL5 exhibited a higher uptake than free RS. Furthermore, confocal images of HepG2 cells after 3 and 5 h of incubation showed higher internalization of coumarin 6 (C6) loaded liposomes (CL) as compared to those of the free C6. Pharmacokinetic and pharmacodynamic (prophylactic and therapeutic treatment modalities) studies were performed in N-nitrosodiethylamine (NDEA-carcinogen) induced HCC in rats. Pharmacokinetic evaluation of RL5 demonstrated increased localization of RS in cancerous liver tissues by 3.2- and 2.2-fold increase in AUC and Cmax, respectively, when compared to those of the free RS group. A pharmacodynamic investigation revealed a significant reduction in hepatocyte nodules in RL5 treated animals when compared to those of free RS. Further, on treatment with RL5, HCC-bearing rats showed a significant decrease in the liver marker enzymes (alanine transaminase, alkaline phosphatase, aspartate transaminase, total bilirubin levels, γ-glutamyl transpeptidase, and α-fetoprotein), in comparison with that of the disease control group. Our findings were supported by histopathological analysis, and we were first to demonstrate that NDEA induced detrimental effect on rat livers was successfully reversed with the treatment of RL5 formulation. These results implied that delivery of RS loaded cationic liposomes substantially controlled the severity of HCC and that they can be considered as a promising nanocarrier in the management of HCC.

Applications of alginate microspheres in therapeutics delivery and cell culture: Past, present and future.

Polymers are the backbone of pharmaceutical drug delivery. There are several polymers with varying properties available today for use in different pharmaceutical applications. Alginate is widely used in biomedical research due to its attractive features such as biocompatibility, biodegradability, inertness, low cost, and ease of production and formulation. Encapsulation of therapeutic agents in alginate/alginate complex microspheres protects them from environmental stresses, including the acidic environment in the gastro-intestinal tract (GIT) and enzymatic degradation, and allows targeted and sustained delivery of the agents. Microencapsulation is playing an increasingly important role in drug delivery as evidenced by the recent surge in research articles on the use of alginate in the delivery of small molecules, cells, bacteria, proteins, vaccines, and for tissue engineering applications. Formulation of these alginate microspheres (AMS) are commonly achieved by conventional external gelation method using various instrumental manipulation such as vortexing, homogenization, ultrasonication or spray drying, and each method affects the overall particle characteristics. In this review, an inclusive summary of the currently available methods for the formulation of AMS, its recent use in the encapsulation and delivery of therapeutics, and future outlook will be discussed.

Local drug delivery systems in the management of periodontitis: A scientific review.

Periodontitis (PD) is a microbial disease of tooth supporting tissues that results in progressive destruction of surrounding soft and hard tissues with eventual tooth mobility and exfoliation. Perioceutics, which includes the delivery of therapeutic agents via systemic and local means as an adjunct to mechanical therapy has revolutionized the arena of periodontal therapy. Selection of a right antimicrobial agent with appropriate route of drug administration is the key to successful periodontal therapy. Irrigating systems, fibers, gels, strips, films, microparticles, nanoparticles and low dose antimicrobial agents are some of the local drug delivery systems (LDDS) available in the field, which aims to deliver antimicrobial agents to sub-gingival diseased sites with minimal or no side-effects on other body sites. The present review aim to summarize the current state-of-the-art technology on LDDS in periodontal therapy ensuring the the practitioners are able to choose LDD agents which are custom made for a specific clinical condition.

Preparation, Optimization, and In Vivo Evaluation of Nanoparticle-Based Formulation for Pulmonary Delivery of Anticancer Drug.

Background and Oobjectives: Lung cancer, a pressing issue in present-day society due to its high prevalence and mortality rate, can be managed effectively by long-term delivery of anticancer agents encapsulated in nanoparticles in the form of inhalable dry powder. This approach is expected to be of strategic importance in the management of lung cancer and is a developing area in current research. In the present investigation, we report on the formulation and characterization of docetaxel inhalable nanoparticles as a viable alternative for effective treatment of non-small cell lung cancer as a long-term delivery choice. Materials and Methods: Poloxamer (PLX-188) coated poly (lactic-co-glycolic acid) (PLGA) nanoparticles containing docetaxel (DTX-NPs) were prepared by simple oil in water (o/w) single emulsification-solvent evaporation process. The nanoparticles were collected as pellet by centrifugation, dispersed in mannitol solution, and lyophilized to get dry powder. Results: Optimized DTX-NPs were smooth and spherical in morphology, had particle size around 200 nm, zeta potential around -36 mV, and entrapment efficiency of around 60%. The invitro anticancer assay was assessed and it was observed that nanoparticle-based formulation exhibited enhanced cytotoxicity when compared to the free form of the drug post 48 h. On examining for invitro drug release, slow but continuous release was seen until 96 h following Higuchi release kinetics. DTX-NPs were able to maintain their desired characteristics when studied at accelerated conditions of stability. Conclusions: In-vivo study indicated that the optimized nanoparticles were well retained in lungs and that the drug level could be maintained for a longer duration if given in the form of DTX-NPs by the pulmonary route. Thus, the non-invasive nature and target specificity of DTX-NPs paves the way for its future use as a pulmonary delivery for treating non-small cell lung cancer (NSCLC).

Phytosynthesis of gold nanoparticles: Characterization, biocompatibility, and evaluation of its osteoinductive potential for application in implant dentistry.

Gold nanoparticles have been extensively used in diagnostics, biomedical imaging, and drug delivery owing to simple method of synthesis and versatile surface functionalization. Present investigation aims to evaluate the osteoinductive property of Salacia chinensis (SC) mediated gold nanoparticles (GNPs) for its application in implant dentistry. The formation of GNPs was assessed initially using the visual method and characterized analytically by using UV-visible spectroscopy, Zetasizer, X-RD, ICP-AES, AFM, and TEM. Green synthesized GNPs exhibited a remarkable stability in various blood components (0.2 M histidine, 0.2 M cysteine 2% bovine serum albumin, and 2% human serum albumin) and were found to be nontoxic when evaluated for their cytocompatibility and blood compatibility using periodontal fibroblasts and erythrocytes respectively. Exposure of GNPs to MG-63 cell lines displayed increased percent cell viability (138 ±â€¯27.4) compared to the control group (96 ±â€¯3.7) which confirms its osteoinductive potential. Herein, it can be concluded that the stable, biocompatible and eco-friendly GNPs can be used as an effective bone inductive agent during dental implant therapy.

Phytosynthesis of Silver Nanoparticles: Characterization, Biocompatibility Studies, and Anticancer Activity.

Silver nanoparticles (SNPs), owing to their wide range of biomedical applications, have recently attracted remarkable interest for use in cancer nanomedicine. The present research work investigated the anticancer activity of phytosynthesized SNPs against human cancer cell lines. Phytosynthesis of SNPs was achieved by using an aqueous extract of Salacia chinensis (SC) bark as a green source to reduce silver nitrate to silver nanoparticles. Characterization of synthesized nanoparticles demonstrated a UV-visible peak at 443 nm, ζ-potential (zetasizer) of -25.6 ± 0.34 and particle size (transmission electron microscopy analysis) in the range of 40-80 nm, which validates formation of stable silver nanoparticles. The absence of cytotoxicity against normal human fibroblasts and blood erythrocytes confirms the biocompatible nature of green synthesized SNPs. In vitro anticancer assay demonstrated IC50 values of 6.31, 4.002, 5.228, 8.452, 14.37, 7.46, and 6.55 µg/mL against liver (Hep G2), lungs (L-132), pancreas (MIA-Pa-Ca-2), breast (MDA-MB-231), oral (KB cells), prostate (PC-3), and cervical (HeLa) cancer cell lines respectively, which confirms its potent anticancer action. The results of the present study give an experimental proof that the SC mediated green synthesized SNPs could serve as a promising anticancer agent to overcome limitations of existing conventional cancer chemotherapeutics.

Formulation of thermoreversible gel of cranberry juice concentrate: Evaluation, biocompatibility studies and its antimicrobial activity against periodontal pathogens.

The present work aims to investigate the efficacy of thermoreversible gel of cranberry juice concentrate (CJC) as local drug delivery for the treatment of periodontitis. CJC was initially tested for its antimicrobial activities like MIC, MBC, antiadhesion, antibiofilm and time kill assay against the panel of organisms (S. mutans (SM), E. faecalis (EF), A. actinomycetemcomitans (AA), P. gingivalis (PG), T. forsythia (TF)) responsible for periapical and periodontal infections. Antimicrobial activity of CJC showed MIC value of 50mg/ml and MBC value of 100mg/ml with desirable antiadhesion (83-90%) and antibiofilm activity (70-85%). CJC was evaluated for its biocompatibility using periodontal fibroblasts by cell based MTT assay and found to be nontoxic. Influence of CJC on periodontopathogen PG derived virulence factors (fimA and kgp) was studied using real time polymerase chain reaction (RT-PCR) technique wherein down regulation of selected genes demonstrated inhibitory effect against PG virulence factors. Thermoreversible gel of CJC was formulated by cold method using poloxamer 407 as thermosensitive polymer and carbopol 934 as mucoadhesive polymer and evaluated for its gelation temperature, viscosity, gel strength and mucoadhesive strength. Comparison of optimized thermoreversible gel of CJC (500mg/ml) with commercially available chlorhexidine gluconate gel (0.2%) using agar well diffusion demonstrated equal zone of inhibition against SM, EF, AA, PG & TF. Hence the formulated thermoreversible gel of CJC could serve as a novel herbal alternative to currently available periodontal treatment modalities.

Effective Cancer Theranostics with Polymer Encapsulated Superparamagnetic Nanoparticles: Combined Effects of Magnetic Hyperthermia and Controlled Drug Release.

A combination of chemotherapy with nonconventional nanoparticle based physical destruction therapy has been proposed clinically to reduce the prospect of evolution of drug resistance in cancer. Superparamagnetic nanoparticles have been actively used for synergetic cancer therapy including magnetic fluid hyperthermia (MFH) guided by magnetic resonance imaging (MRI). To explore this direction of potential applications in cancer therapy, we have functionalized superparamagnetic La0.7Sr0.3MnO3 nanoparticles (SPMNPs) with an oleic acid-polyethylene glycol (PEG) polymeric micelle (PM) structure, and loaded it with anticancer cancer drug doxorubicin (DOX) in a high loading capacity (∼60.45%) for in vitro delivery into cancer cells. The micellar structure provided good colloidal stability and biocompatibility. Upon drug loading, the cancer cell death rate of 89% was comparable to free DOX (75%) for 24 h, and that the counterstrategy of DOX conjugated SPMNPs-induced hyperthermia resulted the cancer cell extinction up to 80% under in vitro conditions within 30 min. In addition, the preliminary effect of protein corona formation on in vitro drug release and delivery was studied. Finally, in vivo bio distribution of micellar SPMNPs is observed in mice model for 50 mg kg-1 dose of SPMNPs. Taken together, polymeric micelle SPMNPs reported here can serve as a promising candidate for effective multimodal cancer theranostics such as in the combined chemotherapy-hyperthermia cancer therapy.

Doxorubicin loaded gold nanoparticles: Implication of passive targeting on anticancer efficacy.

The present work aims to investigate targeting potential of doxorubicin (Dox) functionalized gold nanoparticles (D-GNPs) for treatment of chemically induced fibrosarcoma in mice. Carrier GNPs were synthesised by green chemistry method and loaded with doxorubicin by incubation method. D-GNPs were studied for its biocompatibility using normal mouse fibroblasts (L929) and found to be cell compatible and non-toxic. D-GNPs (at a dose of 2.5, 2 and 1.5mg/kg equivalent to Dox) demonstrated passive targeting measured as function of antitumor efficacy against chemical induced fibrosarcoma which showed higher latency to the tumour growth as compared to free Dox (2.5mg/kg). D-GNPs exhibited significantly higher therapeutic anticancer efficacy (∼81% tumour suppression at dose of 2.5mg/kg equivalent to Dox) in the same model as compared to that of free doxorubicin (∼48% tumour suppression at dose of 2.5mg/kg). Safety profile and targeting efficiency of developed formulation was established by assessing cardiac and blood markers.

Thermoreversible nanoethosomal gel for the intranasal delivery of Eletriptan hydrobromide.

The objective of the current study was to formulate and characterize thermoreversible gel of Eletriptan Hydrobromide for brain targeting via the intranasal route. Ethosomes were prepared by 3(2) factorial design with two independent variables (concentration of soya lecithin and ethanol) and two response variables [percent entrapment efficiency and vesicle size (nm)] using ethanol injection method. Formulated ethosomes were evaluated for preliminary microscopic examination followed by percent drug entrapment efficiency, vesicle size analysis, zeta potential, polydispersibility index and Transmission electron microscopy (TEM). TEM confirms spherical morphology of ethosomes, whereas Malvern zeta sizer confirms that the vesicle size was in the range of 191 ± 6.55-381.3 ± 61.0 nm. Ethosomes were incorporated in gel using poloxamer 407 and carbopol 934 as thermoreversible and mucoadhesive polymers, respectively. Ethosomal gels were evaluated for their pH, viscosity, mucoadhesive strength, in vitro drug release and ex vivo drug permeation through the sheep nasal mucosa. Mucoadhesive strength and pH was found to be 4400 ± 45 to 5500 ± 78.10 dynes/cm(2) and 6.0 ± 0.3 to 6.2 ± 0.1, respectively. In-vitro drug release from the optimized ethosomal gel formulation (G4) was found to be almost 100 % and ex vivo permeation of 4980 µg/ml with a permeability coefficient of 11.94 ± 0.04 × 10(-5) cm/s after 24 h. Histopathological study of the nasal mucosa confirmed non-toxic nature of ethosomal gels. Formulated EH loaded ethosomal thermoreversible gel could serve as the better alternative for the brain targeting via the intranasal route which in turn could subsequently improve its bioavailability.

Green and ecofriendly synthesis of silver nanoparticles: Characterization, biocompatibility studies and gel formulation for treatment of infections in burns.

The current study summarizes a unique green process for the synthesis of silver nanoparticles (AgNPs) by simple treatment of silver nitrate with aqueous extract of Ammania baccifera. Phytosynthesized AgNPs were characterized by various advanced analytical methods and studied for its use against infections associated with burns. Formation of AgNPs was observed by visual color change from colorless to dark brown and confirmed by UV-visible characteristic peak at 436 nm. Zeta potential, particle size and polydispersity index of nano-silver were found to be -33.1 ± 1.12, 112.6 ± 6.8 nm and 0.3 ± 0.06 respectively. XRD spectra revealed crystalline nature of AgNPs whereas TEM confirmed the presence of mixed morphology of AgNPs. The overall approach designated in the present research investigation for the synthesis of AgNPs is based on all 12 principles of green chemistry, in which no man-made chemical other than the silver nitrate was used. Synthesized nano-silver colloidal dispersion was initially tested for minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against a panel of organisms involved in infections associated with burns (Pseudomonas aeruginosa (PA), Staphylococcus aureus (SA) and methicillin resistant S. aureus (MRSA)). MIC and MBC were found to be in range of 0.992 to 7.93 and 7.93 to 31.75 µg/mL respectively. MBC was used for formulation of AgNP gel and tested for its efficacy using agar well diffusion method against PA, SA and MRSA. Comparative bactericidal efficacy of formulated gel (0.03% w/w) and marked formulation Silverex™ ionic (silver nitrate gel 0.2% w/w) showed equal zone of inhibition against all pathogenic bacteria. Formulated AgNP gel consisting of 95% lesser concentration of silver compared to marketed formulation was found to be equally effective against all organisms. Hence, the formulated AgNP gel could serve as a better alternative with least toxicity towards the treatment presently available for infections in burns.

Poloxamer 407-based intranasal thermoreversible gel of zolmitriptan-loaded nanoethosomes: formulation, optimization, evaluation and permeation studies.

Zolmitriptan is the drug of choice for migraine, but low oral bioavailability (<50%) and recurrence of migraine lead to frequent dosing and increase in associated side effects. Increase in the residence time of drug at the site of drug absorption along with direct nose to brain targeting of zolmitriptan can be a solution to the existing problems. Hence, in the present investigation, thermoreversible intranasal gel of zolmitriptan-loaded nanoethosomes was formulated by using mucoadhesive polymers to increase the residence of the drug into the nasal cavity. The preparation of ethosomes was optimized by using 3(2) factorial design for percent drug entrapment efficiency, vesicle size, zeta potential, and polydispersity index. Optimized formulation E6 showed the vesicle size (171.67 nm) and entrapment efficiency (66%) when compared with the other formulations. Thermoreversible gels prepared by using poloxamer 407 showed the phase transition temperature at 32-33 °C which was in line with the nasal physiological temperature. The optimized ethosomes were loaded into the thermoreversible mucoadhesive gel optimized by varying concentrations of poloxamer 407, carbopol 934, HPMC K100, and evaluated for gel strength, gelation temperature, mucoadhesive strength, in vitro drug release, and ex vivo drug permeation, where G3 and G6 were found to be optimized formulations. In vitro drug release was studied by different kinetic models suggested that G3 (n = 0.582) and G6 (n = 0.648) showed Korsemeyer-Peppas (KKP) model indicating non-Fickian release profiles. A permeation coefficient of 5.92 and 5.9 µg/cm(2) for G3 and G6, respectively, revealed very little difference in release rate after 24 h between both the formulations. Non-toxic nature of the gels on columnar epithelial cells was confirmed by histopathological evaluation.

Nepenthes khasiana mediated synthesis of stabilized gold nanoparticles: Characterization and biocompatibility studies.

The current study summarizes a unique green process for the synthesis of gold nanoparticles by simple treatment of gold salts with aqueous extract of Nepenthes khasiana (NK)--a red listed medicinal plant and its characterization. Study on the effect of different process parameters like temperature, pH and stirring on surface and stability characteristics has been demonstrated. Formation of GNPs was visually observed by change in color from colorless to wine red and characterized by UV-Visible spectroscopy, FT-IR spectroscopy, Zetasizer, X-RD, ICP-AES, SEM-EDAX, AFM and TEM. In vitro stability studies of gold colloidal dispersion in various blood components suggest that, NK mediated GNPs exhibit remarkable in vitro stability in 2% bovine serum albumin, 2% human serum albumin (HSA), 0.2M histidine, and 0.2M cysteine but unstable in 5% NaCl solution and acidic pH. Biocompatibility of NK stabilized GNPs against normal mouse fibroblasts (L929) cell lines revealed nontoxic nature of GNPs and thus provides exceptional opportunities for their uses as nanomedicine for diagnosis and drug therapy. The role of antioxidant phytochemicals (flavonoids and polyphenols) of NK extract in synthesis of biocompatible and stabilized GNPs was demonstrated by estimating total flavonoid content, total phenolic content and total antioxidant capacity of extract before and after formation of GNPs. Fast and easy synthesis of biocompatible GNPs possesses unique physical and chemical features which serve as an advantage for its use in various biomedical applications. The overall approach designated in the present research investigation for the synthesis of GNPs is based on all 12 principles of green chemistry, in which no man-made chemical other than the gold chloride was used.

Development of hot melt co-formulated antimalarial solid dispersion system in fixed dose form (ARLUMELT): Evaluating amorphous state and in vivo performance.

The aim of this study was to investigate the industrial feasibility of developing a co-formulated solid dispersion (SD) containing two antimalarial drugs artemether (ARTM) and lumefantrine (LUMF). Soluplus(®) (polyethyleneglycol-polyvinyl caprolactam-polyvinyl acetate grafted copolymer) was used as primary carrier matrices via hot-melt extrusion processing to improve solubility profile and the oral bioavailability of the combination. Based on the preliminary screening, the optimized quantities of PEG 400, Lutrol F127 and Lutrol F68 were incorporated as surfactant with soluplus in different ratios to improve extrudability, increase wettability and the melt viscosity of the HME process. Soluplus(®) was proved to successfully stabilize both the drugs inside its polymeric network during extrusion via forming a stable solid dispersion. Physicochemical properties of the APIs and the SDs characterized by thermo-gravimetric analysis (TGA), differential scanning calorimetry (DSC), MDSC, FTIR spectroscopy and X-ray diffractometry (XRD) revealed the amorphous existence of the drug in all SDs developed. Molecular level morphology of solid dispersion characterized by using advanced physicochemical characterization techniques such as Raman spectroscopy, atomic force microscopy (AFM) and 2D NMR showed the transformation of the crystalline drugs to its stable amorphous state. All manufactured SDs retained their amorphicity even after a stability study conducted in accelerated condition over 6 months. The solubility and in vitro dissolution performance of both drugs in SD formulations was improved significantly when compared with pure drugs and marketed product while the in vivo studies revealed the same.The pharmacokinetic studies in rats revealed that the SD (AL1) shows a 44.12-65.24 folds increase in the AUC(0-72) and 42.87-172.61 folds increase in Cmax compared to that of pure drugs and a better bioavailability than that of commercial product.