Hydrogels for localized drug delivery: A special emphasis on dermatologic applications.

Skin disease treatment is a complex and time-consuming process due to the complex etiology, numerous side effects of conventional therapies, and difficulties in determining primary causes of the disease. Superficial wounds are often easy to treat. However, treatment of severe wounds caused by burn is challenging for clinicians. Optimum therapeutic benefits are based on the site-specific delivery of medicaments at the right time for a prolonged duration. Systemic toxicity and frequent dosing are the major challenges associated with the use of conventional therapeutics. Hydrogels are material of choice for drug delivery because of their high biocompatibility and ability to hold and release therapeutic agents. The number of hydrogels available for use in cosmetology and dermatology continues to grow during the past 1-2 decades. However, new hydrogel materials with high biocompatibility, antibacterial properties, and the ability to stimulate skin regeneration processes are in high demand. These are three-dimensional networks, which absorb a large amount of biological fluids and water. Hydrogels can be used as a biosensor, carrier systems for cells, drug delivery carriers especially for topical applications and in contact lenses. Hydrogels are highly porous carriers containing about 90% water. Stimuli-responsive hydrogels cause a change in network structure that is completely reversible in nature. The present review describes the applications of hydrogels in pharmaceutical formulations with a special emphasis on the treatment of dermatologic conditions such as acne, psoriasis, and mycosis.

Nanomedicine-Based Delivery Strategies for Breast Cancer Treatment and Management.

Breast cancer is one of the most common types of cancer among women globally. It is caused by mutations in the estrogen/progesterone receptors and conventional treatment methods are commonly utilized. About 70-80 percent of individuals with the early-stage non-metastatic disease may be cured. Conventional treatment is far less than the optimal ratio, as demonstrated through the high mortality rate of women with this cancer. However, conventional treatment methods like surgery, radiotherapy, and chemotherapy are not as effective as expected and lead to concerns about low bioavailability, low cellular uptake, emerging resistance, and adverse toxicities. A nanomedicine-based approach is a promising alternative for breast cancer treatment. The present era is witnessing rapid advancements in nanomedicine as a platform for investigating novel therapeutic applications and modern intelligent healthcare management strategies. This paper focuses on nanomedicine-based therapeutic interventions that are becoming more widely accepted for improving treatment effectiveness and reducing undesired side effects in breast cancer patients. By evaluating the state-of-the-art tools and taking the challenges involved into consideration, various aspects of the proposed nano-enabled therapeutic approaches have been discussed in this review.

Effect of papaverine on developmental hyperserotonemia induced autism spectrum disorder related behavioural phenotypes by altering markers of neuronal function, inflammation, and oxidative stress in rats.

Hyperserotonemia, in the early developmental phase, generates a variety of behavioural and biochemical phenotypes associated with autism spectrum disorder (ASD) in rats. Papaverine is known to provide benefits in various brain conditions. We investigated the role of a selective phosphodiesterase-10A (PDE10A) inhibitor, papaverine on ASD related behavioural phenotypes (social behaviour deficits, repetitive behaviour, anxiety and hyperlocomotion) in developmental hyperserotonemia (DHS) rat model. Also, effects on important biochemical markers related with neuronal function (brain-derived neurotrophic factor (BDNF)-neuronal survival and phosphorylated-cAMP response element binding protein (pCREB)-neuronal transcription factor), brain inflammation (interleukin (IL)-6, IL-10 and tumour necrosis factor (TNF)-α) and brain oxidative stress (TBARS and GSH) were studied in important brain areas (frontal cortex, cerebellum, hippocampus and striatum). Administration of a non-selective serotonin receptor agonist, such as 5-methoxytryptamine (5-MT) to rats prenatally (gestational day 12 - day of parturition) and during early stages (postnatal day (PND) 0 -PND20) of development, resulted in impaired behaviour and brain biochemistry. Administration of papaverine (15/30 mg/kg ip) to 5-MT administered rats from PND21 to PND48, resulted in improvement of behavioural deficits. Also, papaverine administration significantly increased the levels of BDNF, pCREB/CREB, IL-10, GSH and significantly decreased TNF-α, IL-6 and TBARS levels in different brain areas. Papaverine, in both doses rectified important behavioural phenotypes related with ASD, the higher dose (30 mg/kg ip) showed significantly greater improvement than 15 mg/kg ip, possibly by improving neuronal function, brain inflammation and brain oxidative stress. Thus, PDE10A could be a probable target for pharmacological interventions and furthering our understanding of ASD pathogenesis.

Formulation and characterization of oral rapid disintegrating tablets of levocetirizine.

BACKGROUND: Levocetirizine, active R (-) enantiomer of cetirizine, is an orally active and selective H1 receptor antagonist used medically as an anti-allergic. Allergic rhinitis is a symptomatic disorder of the nose induced by inflammation mediated by immunoglobulin E (IgE) in the membrane lining the nose after allergen exposure. OBJECTIVES: The purpose of the present study was to prepare rapidly disintegrating tablets of levocetirizine after its complexation with ß-cyclodextrin (ß-CD). MATERIAL AND METHODS: Levocetirizine-ß-CD complex tablets were prepared by direct compression technique using 3 synthetic superdisintegrants in different proportions. Development of the formulation in the present study was mainly based on the concentration of superdisintegrants and the properties of the drug. Nine batches of tablets were formulated and evaluated for various parameters: drug content, weight variation, water absorption ratio, wetting time, in vitro disintegration, hardness, friability, thickness uniformity, and in vitro dissolution. RESULTS: A Fourier-transform infrared spectroscopy (FTIR) study showed that there were no significant interactions between the drug and the excipients. The prepared tablets were good in appearance and showed acceptable results for hardness and friability. The in vitro disintegrating time of the formulated tablet batches was found to be 15-35 s percentage and the drug content of tablets in all formulations was found to be between 90-102%, which complied with the limits established in the United States Pharmacopeia. CONCLUSIONS: Complexation of levocetirizine with ß-CD significantly improves the solubility of the drug. The disintegration time of the tablets was decreased with an increase in superdisintegrant amount. The tablets (batch CPX5) had a minimum disintegration time of 20 s and 99.99% of the drug was released within 10 min.

Development of Ocular Delivery System for Glaucoma Therapy Using Natural Hydrogel as Film Forming Agent and Release Modifier.

BACKGROUND: Glaucoma is characterized by increased intraocular pressure, which results in damage to the optic nerve. The existing therapy with conventional eye drops is inefficient due to nasolachrymal drainage, resulting in a reduced corneal residence of the drug. OBJECTIVES: The objective was to develop controlled-release ocular films of timolol maleate using natural hydrogel from Tamarindus indica seeds as a sustaining and film-forming agent, to overcome the problems associated with eye drops. MATERIAL AND METHODS: The hydrogel was isolated using hot aqueous extraction followed by precipitation with ethanol. Six batches of ocular films were prepared and evaluated for drug content, weight variation, thickness, diameter and in vitro release profile. The ideal batch of the films was subjected to stability, pharmacodynamic and ocular safety studies. RESULTS: The yield of the hydrogel was 58.29%. The thickness of the ocular films was in the range of 0.17 to 0.25 mm and the weight of the films was found to increase with the increase in polymer content. The drug release from the films was found to be controlled over a period of 8 h. The films were found to be stable and were able to reduce the intraocular pressure for 24 h in a more efficient manner than the eye drops. The films were found to be practically non-irritating to the eye. CONCLUSIONS: It can be concluded that the hydrogel from tamarind seeds can be used as a film-forming and release-controlling agent for the development of an ocular drug delivery system for the effective therapy of glaucoma.

Development of novel gastroretentive drug delivery system of gliclazide: hollow beads.

AIM: The current communication deals with the development of hollow floating beads of gliclazide. The primary effect of this drug is to potentiate glucose-stimulated insulin release from pancreatic islet-ß-cells by induction of a decrease in potassium efflux from these cells. Because of the poor aqueous solubility, its absorption is limited. Thus, an attempt was made to improve its release profile. METHODS: The hollow drug-loaded alginate beads in combination with low methoxyl pectin and hydroxypropylmethylcellulose (HPMC) were prepared by a simple ionotropic gelation method. The beads were evaluated for particle size and morphology using optical microscopy and scanning electron microscopy (SEM), respectively. Mucoadhesion test was done using goat stomach mucosal membrane. Release characteristics of the gliclazide-loaded hollow beads were studied in 0.1 N HCl (pH 1.2) and phosphate buffer (pH 5.8). RESULTS: The developed beads were spherical in shape with hollow internal structure and had a particle size in the range of 0.730 ± 0.05 to 0.890 ± 0.03 mm. The incorporation efficiency of alginate -pectin beads was higher than alginate -HPMC beads. The Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction analysis showed stable character of drug in the drug-loaded hollow beads and revealed the absence of any drug -polymer interactions. The beads remained buoyant for more than 12 h. The drug release from beads followed Fickian diffusion with swelling. CONCLUSION: The preliminary results of this study suggest that the developed beads containing gliclazide could enhance drug entrapment efficiency, reduce the initial burst release and modulate the drug release.

Natural mucoadhesive microspheres of Abelmoschus esculentus polysaccharide as a new carrier for nasal drug delivery.

This work describes the preparation and evaluation of mucoadhesive microspheres, using Abelmoschus esculentus polysaccharide as a novel carrier for safe and effective delivery of rizatriptan benzoate into nasal cavity. The polysaccharide was extracted from the fruit of A. esculentus and mucoadhesive microspheres were prepared by emulsification, followed by crosslinking using epichlorohydrin. Prepared microspheres were evaluated for size, morphology, swelling properties, mucoadhesive strength, encapsulation efficiency and drug release. Microspheres were found to release 50% of drug within 15 min and rest of the drug was released within 60 min. The drug release was found to decrease with increasing concentration of polysaccharide. To determine the retention time of the microspheres in the nasal cavity of rabbits, the microspheres were radiolabelled with (99m)Tc and subjected to gamma scintigraphy. The results showed a significant improvement in the nasal retention of the microspheres as compared to the aqueous solution of radiolabelled free-drug.

Topical application of aerial portion of Acalypha indica Linn ameliorates psoriasis in rodents: Evidences from in vivo and in silico studies.

ETHANOPHARMACOLOGICAL RELEVANCE: Acalypha indica Linn. is a weed, used traditionally for different skin diseases such as eczema and dermatitis in various parts of India. There are no previous in vivo studies reported on the antipsoriatic potential of this medicinal plant. AIM: The aim of this study was to investigate antipsoriatic activity of coconut oil dispersion of aerial portion of Acalypha indica Linn. Few lipid-soluble phytoconstituents of this plant were subjected to molecular docking studies on different targets to determine phytoconstituent responsible for antipsoriatic activity. METHODS: Virgin coconut oil dispersion of aerial portion of the plant was prepared by mixing three parts of coconut oil and one part of powdered aerial portion. The acute dermal toxicity was determined according to OECD guidelines. Mouse tail model was used to evaluate the antipsoriatic activity. Molecular docking of phytoconstituents was carried out using Biovia Discovery Studio. RESULTS: In acute dermal toxicity study,the coconut oil dispersion was found to be safe up to the dose of 20000 mg/kg. The dispersion exhibited significant antipsoriatic activity (p < 0.01) at the dose of 250 mg/kg; at 500 mg/kg dose, the activity was similar that of 250 mg/kg dose. In the docking study of the phytoconstituents, 2-methyl anthraquinone was found to be responsible for antipsoriatic activity. CONCLUSION: This study provides new evidence of Acalypha indica Linn as antipsoriatic plant and justifies its traditional use. Computational studies also endorse the results obtained via acute dermal toxicity study and mouse tail model for evaluation of antipsoriatic potential.

Behavioral and biochemical investigations to explore the efficacy of quercetin and folacin in experimental diabetes induced vascular endothelium dysfunction and associated dementia in rats.

OBJECTIVES: Vascular dementia (VaD), being strongly associated with metabolic conditions is a major health concern around the world. Diabetes is a major risk factor for the development of VaD. This study investigates the efficacy of quercetin and folacin in diabetes induced vascular endothelium dysfunction and related dementia. METHODS: Single dose streptozotocin (STZ) (50 mg/kg i.p) was administered to albino Wistar rats (male, 200-250 g) by dissolving in citrate buffer. Morris water maze (MWM) and attentional set shifting tests were used to assess the spatial learning, memory, reversal learning, and executive functioning in animals. Body weight, serum glucose, serum nitrite/nitrate, vascular endothelial function, aortic superoxide anion, brains' oxidative markers (thiobarbituric acid reactive species-TBARS, reduced glutathione-GSH, superoxide dismutase-SOD, and catalase-CAT), mitochondrial enzyme complex (I, II, and IV), inflammatory markers (interleukin-IL-6, IL-10, tumor necrosis factor-TNF-α, and myeloperoxidase-MPO), and acetylcholinesterase activity-AChE were also assessed. Quercetin (30 mg kg-1/60 mg kg-1) and folacin (30 mg kg-1/60 mg kg-1) were used as the treatment drugs. Donepezil (0.5 mg kg-1) was used as a positive control. RESULTS: STZ administered rats showed reduction in learning, memory, reversal learning, executive functioning, impairment in endothelial function, increase in brains' oxidative stress; inflammation; AChE activity, and decrease in mitochondrial complex (I, II, and IV) activity. Administration of quercetin and folacin in two different doses, significantly attenuated the STZ induced diabetes induced impairments in the behavioral, endothelial, and biochemical parameters. CONCLUSIONS: STZ administration caused diabetes and VaD which was attenuated by the administration of quercetin and folacin. Therefore, these agents may be studied further for the assessment of their full potential in diabetes induced VaD conditions.

Nanovaccine: A Hope to Triumph the Battle Against Novel Coronavirus Disease 2019 (COVID-19).

BACKGROUND: The novel coronavirus 2019 (COVID-19) infection has caused the global emergence of coronavirus in humans during the last 12 months. Till May 11, 2021, the confirmed global COVID-19 cases and deaths reached 158551526 and 3296855, respectively. METHODS: Goblet cells and ciliated cells in the nose act as the initial infection site of SARS-CoV-2. Thus, mucus immunity is important to protect from infection. The outburst of SARS-CoV-2 infection can be halted only when an effective vaccine will be developed. RESULTS: Globally, over 100 different vaccines are under investigation, including DNA vaccines, RNA vaccines, inactivated virus vaccines, adenovirus-based vaccines, recombinant/subunit protein vaccines, peptide vaccines, virus-like particles, etc. Inactivated virus vaccines and mRNA, and adenovirus-based vaccines have moved fast into patent clinical trials. CONCLUSION: Vaccines containing spike protein of SARS-CoV as subunit could effectively prevent binding of coronavirus to the host cell and membrane fusion. Thus, spike protein can be used as a major target for subunit vaccine preparation.

Optimization studies on gastroretentive floating system using response surface methodology.

The aim of the present investigation was to develop and optimize gastroretentive floating system of amoxicillin for the efficient treatment of peptic ulcer induced by Helicobacter pylori infection. Floating microballoons were developed using central composite design (CCD), and optimization was done by employing response surface methodology. The selected independent variables were cellulose acetate phthalate, drug-Eudragit S100 ratio, and the ratio of dichloromethane/ethanol/isopropyl alcohol. The selected dependent variables were yield, mean particle size, buoyancy, encapsulation efficiency, and drug release within 8 h. A quadratic polynomial model was generated which had linear, interaction, and quadratic terms to predict and evaluate the independent variables with respect to the dependent variables. Results showed that selected independent variables significantly affect the yield (30.53-82.71%), particle size (31.62-47.03 µm), buoyancy (42.68-95.75%), encapsulation efficiency (56.96-93.13%), and cumulative drug release from the microballoons (34.01-74.65%). The interaction and quadratic terms were also found to affect the process variables. An excellent agreement was found between the actual value and predicted value. In conclusion, it can be said that CCD is a valuable second-degree design to develop and optimize GFS of amoxicillin which in turn provides a basis to localize the drug release in the gastric region for effective treatment of H. pylori-mediated infection.

Vinpocetine ameliorates developmental hyperserotonemia induced behavioral and biochemical changes: role of neuronal function, inflammation, and oxidative stress.

Hyperserotonemia, during the early developmental phase, generates behavioral and biochemical phenotypes associated with autism spectrum disorder (ASD) in rats. Phosphodiesterase­1 (PDE1) inhibitors are known to provide benefits in various brain conditions. We investigated the role of a selective PDE1 inhibitor, vinpocetine on ASD­related behavioral phenotypes (social behavioral deficits, repetitive behavior, anxiety, and hyperlocomotion) in a developmental hyperserotonemia (DHS) rat model. Also, effects on biochemical markers related with neuronal function brain derived neurotrophic factor (BDNF) and phosphorylated cAMP response element binding protein (pCREB), inflammation interleukins (IL­6 and IL­10) and tumor necrosis factor-alpha (TNF­α), and oxidative stress (TBARS and GSH) were studied in important brain areas (frontal cortex, cerebellum, hippocampus, and striatum). Administration of 5­methoxytryptamine (5­MT) to rats prenatally (gestational day 12) and in early developmental stages postnatal day (PND 0 - PND 20), resulted in impaired behavior and brain biochemistry. Administration of vinpocetine daily (10 and 20 mg/kg) to 5­MT rats from PND 21 to PND 48 resulted in an improvement of behavioral deficits. Also, vinpocetine administration significantly increased the levels of BDNF, ratio of pCREB/ CREB, IL­10, and GSH, and significantly decreased TNF­α, IL­6, and TBARS levels in different brain areas. Finally, our correlation analysis indicated that behavioral outcomes were significantly associated with the biochemical outcome. Vinpocetine, a selective PDE1 inhibitor, rectified important behavioral phenotypes related with ASD, possibly by improving markers of neuronal function, brain inflammation, and brain oxidative stress. Thus, PDE1 could be a potential target for pharmacological interventions and furthering our understanding of ASD pathogenesis.

Therapeutic Potential of Antileukotriene Drug-Camellia sinensis Extract Co-Formulation on Histamine Induced Asthma in Guinea Pigs.

BACKGROUND/OBJECTIVE: To study the therapeutic potential of Antileukotriene drug- Camellia sinensis extract co-formulation on histamine induced asthma in guinea pigs. METHODS: SRSD of Montelukast sodium was prepared by the solvent evaporation method. Lyophilized aqueous extract of Camellia sinensis leaves and SRSD mixture was filled in capsule and the capsule shell was coated to achieve initial release lag time. In vitro and pharmacokinetic study of capsules was performed and compared with commercial tablets. A further role of green tea, as an antioxidant adjunct for asthma management, has been analyzed by lung histology, mast cell count and oxidative stress assay in the serum of control and experimental animals. RESULTS: The drug release from the commercial tablet was immediate and rapid, but capsule has shown an initial 3.5 hr lag time followed by sustained action up to 8 hr. Pharmacokinetic results show that studied formulations are bioequivalent with respect to Cmax and AUC, while rest parameters showed asignificant difference. Mast cells count in lung tissue were increased (p<0.001) in the experimental group along with glycoprotein deposition in asthmatic bronchioles. Levels of SOD and GPX were decreased (p<0.05) while CAT was increased (p<0.04) in the asthma group in comparison to control. CONCLUSION: In the experimental animal model, co-formulation was effective in modulating allergic inflammation and contributing to better control of the inflammatory response. Our findings suggest that Camellia sinensis leaves extract may be used as an adjunct for future improvements in asthma treatment and prevention.

Cilostazol attenuated prenatal valproic acid-induced behavioural and biochemical deficits in a rat model of autism spectrum disorder.

OBJECTIVES: Autism spectrum disorder (ASD) is categorized as a neurodevelopmental disorder, presenting with a variety of aetiological and phenotypical features. Inhibiting the enzyme phosphodiesterase-3 (PDE3) with cilostazol is known to produce beneficial effects in several brain disorders. The pharmacological outcome of cilostazol administration was investigated in prenatal valproic acid (VPA)-induced ASD deficits in albino Wistar rats. METHODS: Cilostazol was administered in two doses (30/60 mg/kg) to male rats born of females administered with VPA on gestational day 12. Behavioural assays on locomotion (open field), social interaction, repetitive behaviour (y-maze) and anxiety (elevated plus maze) were performed in all groups. Further, biochemical assessments of markers associated with neuronal function (BDNF, pCREB), inflammation (TNF-α, IL-6, IL-10) and oxidative stress were carried out in frontal cortex, hippocampus, striatum and cerebellum. KEY FINDINGS: The cilostazol regimen, attenuated prenatal VPA exposure associated hyperlocomotion, social interaction deficits, repetitive behavior, and anxiety. Further, biochemical markers such as BDNF, pCREB, IL-10 and GSH were found to be significantly increased contrary to markers such as TNF-α, IL-6 and TBARS in the assessed brain regions. CONCLUSIONS: Cilostazol rectified core behavioural traits while producing significant changes to biochemistry in the brain, suggesting benefits of cilostazol administration in experimental models of ASD.

Protein-Based Nanohydrogels for Bioactive Delivery.

Hydrogels possess a unique three-dimensional, cross-linked network of polymers capable of absorbing large amounts of water and biological fluids without dissolving. Nanohydrogels (NGs) or nanogels are composed of diverse types of polymers of synthetic or natural origin. Their combination is bound by a chemical covalent bond or is physically cross-linked with non-covalent bonds like electrostatic interactions, hydrophobic interactions, and hydrogen bonding. Its remarkable ability to absorb water or other fluids is mainly attributed to hydrophilic groups like hydroxyl, amide, and sulphate, etc. Natural biomolecules such as protein- or peptide-based nanohydrogels are an important category of hydrogels which possess high biocompatibility and metabolic degradability. The preparation of protein nanohydrogels and the subsequent encapsulation process generally involve use of environment friendly solvents and can be fabricated using different proteins, such as fibroins, albumin, collagen, elastin, gelatin, and lipoprotein, etc. involving emulsion, electrospray, and desolvation methods to name a few. Nanohydrogels are excellent biomaterials with broad applications in the areas of regenerative medicine, tissue engineering, and drug delivery due to certain advantages like biodegradability, biocompatibility, tunable mechanical strength, molecular binding abilities, and customizable responses to certain stimuli like ionic concentration, pH, and temperature. The present review aims to provide an insightful analysis of protein/peptide nanohydrogels including their preparation, biophysiochemical aspects, and applications in diverse disciplines like in drug delivery, immunotherapy, intracellular delivery, nutraceutical delivery, cell adhesion, and wound dressing. Naturally occurring structural proteins that are being explored in protein nanohydrogels, along with their unique properties, are also discussed briefly. Further, the review also covers the advantages, limitations, overview of clinical potential, toxicity aspects, stability issues, and future perspectives of protein nanohydrogels.

Vinpocetine amended prenatal valproic acid induced features of ASD possibly by altering markers of neuronal function, inflammation, and oxidative stress.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex etiology and phenotypes. Phosphodiesterase-1 (PDE1) inhibitors are known to provide benefits in various brain conditions manifesting similar behavioral phenotypes. The pharmacological consequences of vinpocetine administration a PDE1 inhibitor in prenatal-valproic acid (pre-VPA) induced ASD related behavioral phenotypes (social behavior deficits, repetitive behavior, anxiety, hyperlocomotion, and nociception) was assessed. Also, effects on important biochemical markers of neuronal function (DCX-neurogenesis, BDNF-neuronal survival, synapsin-IIa-synaptic transmission, pCREB-neuronal transcription factor), inflammation (interleukin [IL]-6, IL-10, and TNF-α) and oxidative stress (thiobarbituric acid reactive substance [TBARS] and glutathione (GSH) were studied in important brain areas (frontal cortex, cerebral cortex, hippocampus, and striatum). Further, neuronal cell viability was determined in dentate gyrus using Nissl staining. Pre-VPA administration resulted into impaired behavior, brain biochemistry, and neuronal cell viability. Administration of vinpocetine resulted in improvements of pre-VPA impaired social behavior, repetitive behavior, anxiety, locomotion, and nociception. Also, vinpocetine resulted in a significant increase in the levels of BDNF, synapsin-IIa, DCX, pCREB/CREB, IL-10, and GSH along with significant decrease in TNF-α, IL-6, TBARS, number of pyknotic and chromatolytic cells in different brain areas of pre-VPA group. Finally, high association between behavioral parameters and biochemical parameters was observed upon Pearson's correlation analysis. Vinpocetine, a PDE1 inhibitor rectified important behavioral phenotypes related with ASD, possibly by improving neuronal function, brain inflammation and brain oxidative stress. Thus, PDE1 may be a possible target for further understanding ASD. LAY SUMMARY: ASD is a brain developmental disorder with a wide array of genetic and environmental factors. Many targets have been identified till date, but a clinical treatment is still afar. The results of this study indicate that vinpocetine administration resulted in amelioration of ASD associated symptomatology in rats, prenatally exposed to VPA. Our research adds a widely expressed brain enzyme PDE1, as a possible novel pharmacological target and opens-up a new line of enquiry for ASD treatment.

Lipid Nanoparticles as Carriers for Bioactive Delivery.

Nanotechnology has made a great impact on the pharmaceutical, biotechnology, food, and cosmetics industries. More than 40% of the approved drugs are lipophilic and have poor solubility. This is the major rate-limiting step that influences the release profile and bioavailability of drugs. Several approaches have been reported to administer lipophilic drugs with improved solubility and bioavailability. Nanotechnology plays a crucial role in the targeted delivery of poorly soluble drugs. Nanotechnology-based drug delivery systems can be classified as solid lipid nanoparticulate drug delivery systems, emulsion-based nanodrug delivery systems, vesicular drug delivery systems, etc. Nanotechnology presents a new frontier in research and development to conquer the limitations coupled with the conventional drug delivery systems through the formation of specific functionalized particles. This review presents a bird's eye view on various aspects of lipid nanoparticles as carriers of bioactive molecules that is, synthesis, characterization, advantage, disadvantage, toxicity, and application in the medical field. Update on recent development in terms of patents and clinical trials of solid lipid nanoparticles (SLNs) and nanostructure lipid carriers (NLCs) have also been discussed in this article.

Attenuation of neurobehavioural abnormalities by papaverine in prenatal valproic acid rat model of ASD.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex aetiology and phenotypes. Phosphodiesterase-10A (PDE10A) inhibition has shown to provide benefits in various brain conditions. We investigated the role of a PDE10A inhibitor, papaverine on core phenotypes in prenatal-valproic acid (Pre-VPA) model of ASD. In order to identify probable mechanisms involved, the effects on several protein markers of neuronal function such as, neurogenesis-DCX, neuronal survival-BDNF, synaptic transmission-synapsin-IIa, neuronal transcription factor-pCREB, neuronal inflammation (IL-6, IL-10 and TNF-α) and neuronal oxidative stress (TBARS and GSH) were studied in frontal cortex, cerebellum, hippocampus and striatum. Pre-VPA induced impairments in social behaviour, presence of repetitive behaviour, hyper-locomotion, anxiety, and diminished nociception were studied in male Albino Wistar rats. Administration of papaverine to Pre-VPA animals resulted in improvements of social behaviour, corrected repetitive behaviour, anxiety, locomotor, and nociceptive changes. Also, papaverine resulted in a significant increase in the levels of BDNF, synapsin-IIa, DCX, pCREB, IL-10 and GSH along with significant decrease in TNF-α, IL-6 and TBARS in different brain areas of Pre-VPA group. Finally, high association between behavioural parameters and biochemical parameters was observed upon Pearson's correlation analysis. Papaverine, administration rectified core behavioural phenotype of ASD, possibly by altering protein markers associated with neuronal survival, neurogenesis, neuronal transcription factor, neuronal transmission, neuronal inflammation, and neuronal oxidative stress. Implicating PDE10A as a possible target for furthering our understanding of ASD phenotypes.

Topical delivery of Tacrolimus using liposome containing gel: An emerging and synergistic approach in management of psoriasis.

Psoriasis is a chronic relapsing inflammatory and hyperproliferative skin disease affecting quality of life. It affects an estimated 8 million Americans and more than 125 million people worldwide. The estimated cost to treat psoriasis in USA is over 13 billion US dollars per year. Treatment of psoriasis may include topical steroid-sparing agent, topical corticosteroids, phototherapy or biologics. Tacrolimus has 10-fold greater immunosuppressive activity than the ciclosporin A which has been recommended for effective treatment of psoriasis. However, it has been widely investigated using conventional formulation approaches which limit its clinical outcomes. It has poor cutaneous bioavailability when administered topically using conventional delivery approach, thus it has poor efficacy against the psoriasis. Low aqueous solubility and high degradation of Tacrolimus make it difficult to formulate as a liquid preparation. Moreover, Tacrolimus has narrow therapeutic index and thus it is essential to prevent its possible toxic effects when a modified release dosage form is administered. The present hypothesis aims to put forward to incorporate Tacrolimus into a novel lipid based nanocarrier system, which would be further loaded into a hydrogel base and evaluated for its target specific topic delivery. Due to the structural similarity of the lipid nanocarriers and skin, these vesicles would target the skin tissues effectively and treat psoriasis with minimum or no side effects. Thus, the proposed formulation would be a considerable value addition to the current therapeutic approaches used for psoriasis management.

Nanoantibiotic Formulations to Combat Antibiotic Resistance - Old Wine in a New Bottle.

Antibiotic resistance is becoming one of the major obstacles to treatment success in various pathological conditions. Development process of a new antimicrobial agent is slow and difficult, whereas bacterial resistance is decreasing the arsenal of existing antibiotics. Therefore, there is a need to develop novel antibiotic formulations to combat the resistance of existing antibiotics. Nanoparticles are investigated as novel antibiotic formulation, but are often inefficient in practical applications. Nanotechnology presents a new frontier to overcome the issue of antibiotic resistance through the development of functionalized particles. Balance of physicochemical characteristics such as small particle size and high drug loading capacity along with improved stability are the challenges associated with large scale manufacturing of nanoantibiotic formulations. In the last 1-2 decades, a gradual increase in patents on nanoantibiotic formulations has been noted to address the resistance issues of antibiotic. The aim of this review is to consolidate recently-investigated nanoantibiotic formulations to combat antibiotic resistance.