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Normal skin is the first line of defense in the human body. A burn injury makes the skin susceptible to bacterial infection, thereby delaying wound healing and ultimately leading to sepsis. The chances of biofilm formation are high in burn wounds due to the presence of avascular necrotic tissue. The most common pathogen to cause burn infection and biofilm is Pseudomonas aeruginosa. The purpose of this study was to create a microemulsion (ME) formulation for topical application to treat bacterial burn infection. In the present study, tea tree oil was used as the oil phase, Tween 80 and transcutol were used as surfactants, and water served as the aqueous phase. Pseudo ternary phase diagrams were used to determine the design space. The ranges of components as suggested by the design were chosen, optimization of the microemulsion was performed, and in vitro drug release was assessed. Based on the characterization studies performed, it was found that the microemulsion were formulated properly, and the particle size obtained was within the desired microemulsion range of 10 to 300 nm. The I release study showed that the microemulsion followed an immediate release profile. The formulation was further tested based on its ability to inhibit biofilm formation and bacterial growth. The prepared microemulsion was capable of inhibiting biofilm formation. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), a neurodegenerative condition previously known to affect the older population, is also now seen in younger individuals. AD is often associated with cognitive decline and neuroinflammation elevation primarily due to amyloid β (Aβ) accumulation. Multiple pathological complications in AD call for therapies with a wide range of neuroprotection. Our study aims to evaluate the effect of N-acetyl-L-tryptophan (NAT) in ameliorating the cognitive decline and neuroinflammation induced by Aβ 1-42 oligomers and to determine the therapeutic concentration of NAT in the brain. We administered Aβ 1-42 oligomers in rats via intracerebroventricular (i.c.v.) injection to induce AD-like conditions. The NAT-treated animals lowered the cognitive decline in the Morris water maze characterized by shorter escape latency and increased path efficiency and platform entries. Interestingly, the hippocampus and frontal cortex showed downregulation of tumor necrosis factor, interleukin-6, and substance P levels. NAT treatment also reduced acetylcholinesterase activity and total and phosphorylated nuclear factor kappa B and Tau levels. Lastly, we observed upregulation of cAMP response element-binding protein 1 (CREB1) signaling. Surprisingly, our HPLC method was not sensitive enough to detect the therapeutic levels of NAT in the brain, possibly due to NAT concentrations being below the lowest limit of quantification of our validated method. To summarize, the administration of NAT significantly lowered cognitive decline, neuroinflammatory pathways, and Tau protein and triggered the upregulation of CREB1 signaling, suggesting its neuroprotective role in AD-like conditions. [ABSTRACT FROM AUTHOR]

Curcumin (CUR) is a phytochemical widely used in food industries, cosmetics, and in the treatment of various ailments. It is a polyphenol derived from turmeric and is often considered the golden spice. CUR has a low solubility of less than 1 µg/ml and poor oral bioavailability which can be improved by co-amorphization with naringin (NRG). Analytical method to simultaneously quantify CUR and NRG is not reported in literature. This study aimed to develop a stability-indicating reverse phase HPLC method in gradient mode to simultaneously quantify CUR and NRG in co-amorphous system. The co-amorphous system of CUR and NRG in molar ratios 1:1 and 1:2 was prepared by quench cooling technique. The separation was attained on a Genesis C18, (4.6 mm × 150 mm, 4 µm) column with the mobile phase comprising of methanol and a 0.1% acetate buffer pH 3.8 at a single wavelength, 289 nm. CUR and NRG eluted at 5.1 and 11.1 min, respectively. For both the molecules, the linearity range was 0.125–16 µg/ml with LOD and LOQ of 0.063 and 0.125 µg/ml. The method developed was validated as per International Conference on Harmonization (ICH) guidelines for linearity, accuracy, precision, and robustness. The method was used to estimate CUR and NRG content in co-amorphous mixture and for in vitro evaluation. [ABSTRACT FROM AUTHOR]

Fungal keratitis, an ocular fungal infection, is one of the leading causes of monocular blindness. Natamycin has long been considered the mainstay drug used for treating fungal keratitis and is the only US Food and Drug Administration (USFDA)-approved drug, commercially available as a topical 5% w/v suspension. Furthermore, ocular fungal infection treatment takes a few weeks to months to recover, and the available marketed antifungal suspensions are associated with poor residence time, limited bioavailability (< 5%) and high dosing frequency as well as minor irritation and discomfort. Despite these challenges, natamycin is still the preferred drug choice for treating fungal keratitis, as it has fewer side effects and less ocular toxicity and is more effective against Fusarium species than other antifungal agents. Several novel therapeutic approaches for the topical delivery of natamycin have been reported to overcome the challenges posed by the conventional dosage forms and to improve ocular bioavailability for the efficient management of fungal keratitis. Current progress in the delivery systems uses approaches aimed at improving the corneal residence time, bioavailability and antifungal potency, thereby reducing the dose and dosing frequency of natamycin. In this review, we discuss the various strategies explored to overcome the challenges present in ocular drug delivery of natamycin and improve its bioavailability for ocular therapeutics. [ABSTRACT FROM AUTHOR]

Cervical cancer is an aggressive type of cancer affecting women worldwide. Many affected individuals rely on smear tests for the diagnosis, surgery, chemotherapy, or radiation for their treatment. However, due to a broad set of undesired results and side-effects associated with the existing protocols, the search for better diagnostic and therapeutic interventions is a never-ending pursuit. In the purview, the bio-concentration of trace elements (copper, selenium, zinc, iron, arsenic, manganese, and cadmium) is seen to fluctuate during the occurrence of cervical cancer and its progression from pre-cancerous to metastatic nature. Thus, during the occurrence of cervical cancer, the detection of trace elements and their supplementation will prove to be highly advantageous in developing diagnostic tools and therapeutics, respectively. This review provides a detailed overview of cervical cancer, its encouragement by human papillomavirus infections, the mechanism of pathology, and resistance. Majorly, the review emphasizes the less explored role of trace elements, their contribution to the growth and inhibition of cervical cancer. Numerous clinical trials have been listed, thereby providing a comprehensive reference to the exploration of trace elements in the management of cervical cancer. [ABSTRACT FROM AUTHOR]

Curcumin (CUR), a natural polyphenolic compound extracted from the rhizomes of Curcuma longa, is used as a pharmaceutical agent, spice in food, and as a dye. Currently, CUR is being investigated for cancer treatment in Phase-II clinical trials. CUR also possesses excellent activities like anti-inflammatory, anti-microbial, and anti-oxidant, therefore quality control is crucial. The present research work was to develop a new, simple, validated and time-saving rapid 96-well plate spectrofluorimetric method for the determination of CUR. The developed method was compared with routinely used high performance liquid chromatography (HPLC) technique. The developed method were found to be linear in the concentration range of 15 to 3900 ng/mL with R2 ≥ 0.9983 for spectrofluorimetric and 50-7500 ng/mL with R2 ≥ 0.9999 for HPLC method. Accuracy, intraday and interday precision was adequate, with RSD lower than the suggested limits. The limits for the detection and the quantification of CUR were 7 and 15 ng/mL for spectrofluorimetric, and 25 and 50 ng/mL for HPLC respectively. The Bland-Altman analysis demonstrated the similarities between the two methods. The 96-well plate method was successfully applied to determine CUR in solid lipid nanoparticles (SLNs) and chitosan nanoparticles (Chi-NPs). The developed spectrofluorimetric method can hence serve as a possible replacement for the HPLC method for the quantification of CUR in healthcare and food products. [ABSTRACT FROM AUTHOR]

Derma roller, a device rolled onto the skin to form micropores, is extensively used for cosmetic purposes. The pores thus created are utilized to either result in the induction of collagen production, leading to glowing and wrinkle-free skin or for permeating the applied formulations to the site of action within the skin. Recent studies have shown the benefits of using derma rollers for transdermal delivery of drugs. In the nascent stage, this approach paves a way to successfully breach the stratum corneum and aid in the movement of medications directed towards the dermis and the hair follicles. The review essentially summarizes the evidence of the use of derma rollers in cosmetic setup, their designing, and the preclinical and clinical reports of efficacy, safety, and concerns when translated for pharmaceutical purposes and transdermal drug delivery. [ABSTRACT FROM AUTHOR]

Pentoxifylline (PTX), an anti-hemorrhage drug used in the treatment of intermittent claudication, is extensively metabolized by the liver resulting in a reduction of the therapeutic levels within a short duration of time. Self-nano-emulsifying drug delivery system (SNEDDS) is well reported to enhance the bio-absorption of drugs by forming nano-sized globules upon contact with the biological fluids after oral administration. The present study aimed to formulate, characterize, and improve the oral bioavailability of PTX using SNEDDS. The formulated SNEDDS consisted of palm oil, Capmul® MCM, and Tween® 80 as oil, surfactant, and co-surfactant, respectively. The mixture design module under the umbrella of the design of experiments was used for the optimization of SNEDDS. The dynamic light-scattering technique was used to confirm the formation of nanoemulsion based on the globule size, in addition to the turbidity measurements. In vivo bioavailability studies were carried out on male Wistar rats. The pharmacokinetic parameters upon oral administration were calculated using the GastroPlus software. The optimized SNEDDS had a mean globule size of 165 nm with minimal turbidity in an aqueous medium. Bioavailability of PTX increased 1.5-folds (AUC = 1013.30 ng h/mL) as SNEDDS than the pure drug with an AUC of 673.10 ng h/mL. In conclusion, SNEDDS was seen to enhance the bioavailability of PTX and can be explored to effectively control the incidents of intermittent claudication. [ABSTRACT FROM AUTHOR]

This study investigated the dissolution behavior of BCS class II ionizable weak base Saquinavir and its mesylate salt in the multi-compartment transfer setup employing different composition of dissolution media. The dissolution behavior of Saquinavir was studied by using a two-compartment transfer model representing the transfer of drug from the stomach (donor compartment) to the upper intestine (acceptor compartment). Various buffers like phosphate, bicarbonate, FaSSIF, and FeSSIF were employed. The dissolution was also studied in the concomitant presence of the additional solute, i.e., Quercetin. Further, the dissolution profiles of Saquinavir and its mesylate salt were simulated by GastroPlusTM, and the simulated dissolution profiles were compared against the experimental ones. The formation of in situ HCl salt and water-soluble amorphous phosphate aggregates was confirmed in the donor and acceptor compartments of the transfer setup, respectively. As the consequence of the lower solubility product of HCl salt of Saquinavir, the solubility advantage of mesylate salt was vanished leading to the lower than the predicted dissolution in the acceptor compartment. However, the formation of water-soluble aggregates in the presence of the phosphate salts was observed leading to the higher than the predicted dissolution of the free base in the transfer setup. Interestingly, the formation of such water-soluble aggregates was found to be hindered in the concomitant presence of an ionic solute resulting in the lower dissolution rates. The in situ generation of salts and aggregates in the transfer model lead to the inconsistent prediction of dissolution profiles by GastroPlusTM. [ABSTRACT FROM AUTHOR]

Adapalene-loaded transfersome gel containing vitamin C as a combination therapy for the management of acne vulgaris was developed in the present study. The transfersome was prepared by reverse-phase evaporation, and the effect of various process parameters were investigated by the Design of Experiment (DOE) approach and optimized based on the particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE). The selected tranfersomes were further evaluated for their thermal behavior and morphology by transmission electron microscopy and turbidity measurements and incorporated into a gel with/without vitamin C. The gel was evaluated and compared with the marketed product (Adiff gel) for various physicochemical parameters, and in vivo studies in testosterone-induced rat models of acne. The prepared transfersomes had PS in the range of 280 to 400 nm, PDI values of 0.416 to 0.8, ZP of − 38 to − 20 mV, and % EE of 32 to 70%. DSC studies confirmed a positive interaction of the components in the transfersome. Surface morphology confirmed that the vesicles were spherical, unilamellar, and discrete. A relative deformability study showed higher elasticity of the transfersomes compared with Adiff aqs gel. Ascorbyl-6-palmitate in adapalene-loaded transfersome gel containing vitamin C (ADVTG) was found to have a good antioxidant free radical–scavenging activity. An in vitro drug release study showed that the sustained release of the transfersomal formulations was attributed to the flexibility of the vesicles by which penetration was increased. ADVTG was found to be promising in treating acne compared with the marketed product. [ABSTRACT FROM AUTHOR]

In the past decade, research in the area of nanodrug delivery has reached a new height with the advent of lipid based nanodrug delivery systems. Lipids being biocompatible and possessing diverse physicochemical properties have tremendous potential to enhance oral bioavailability of water insoluble drugs. Incorporation of a drug in lipid carriers is a smart approach to overcome problems related with conventional oral therapy. In recent years, two lipid based nanoparticles, namely solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are widely explored. SLN are spherical nanoparticles with a drug-containing solid lipid core stabilized with surfactants and formulated mainly to improve bioavailability of the drug molecules. Despite several advantages of SLNs, their major drawbacks include limited drug loading, drug leakage, and crystallization during storage. These drawbacks were avoided or reduced by the development of a new generation of lipid nanoparticles, the NLC, wherein a solid lipid is blended with liquid lipid. Modulation of drug release was added advantage with NLC formulations. The present review focuses on production techniques, characterization, release characteristics, stability, toxicity and potential applications of SLNs and NLCs. [ABSTRACT FROM AUTHOR]

Telmisartan (TEL) is a poorly bioavailable antihypertensive drug candidate owing to its low solubility in all the biofluids. The present study is aimed to enhance the solubility of TEL by forming an inclusion complex with sulfobutylether beta-cyclodextrin (SBE-β-CD), discover its mode of inclusion and predict the bioavailability of the prepared complexes. The formation of the inclusion complex is explained based on the hydrogen bond propensities and molecular dynamics simulations. Freeze-drying method was employed for the preparation of inclusion complexes. These complexes were subsequently characterized by powder X-ray diffraction, differential scanning calorimetry, and Fourier transform-infrared spectroscopy. The spatial configuration of the drug inside the cyclodextrin cavity is probed using 1H and 13C NMR. The in silico docking results are in good agreement with the experimental data and reveal that the hydrogen bond is formed as a part of the guest molecule enters from the broader end of the ring and the protons at the interior portion of the molecule interact with the carboxylic acid (-COOH) group of TEL leading to the formation of a hydrogen bond. The phenyl moiety of TEL occupies the central core and forms multiple Van-der-Waals interactions with the glucopyranose units of the SBE-β-CD. The inclusion complex demonstrates significantly higher in vitro dissolution profile as compared with plain TEL. The GastroPlus™ simulation software generated parameters of inclusion complex in comparison to plain TEL show a seven fold increase in Cmax and 18 fold increase in bioavailability. [ABSTRACT FROM AUTHOR]

Purpose: A non-propellant based foam (NPF) system was developed incorporating the antibiotics, pectin capped green nano-silver and sulfadiazine (SD) for the topical treatment of burn wounds as a convenient alternative to the existing therapies. Methods: NPF were prepared using various surfactants and oils forming a nanoemulsion. Anti-microbial studies by resazurin microtitre assay, ex vivo diffusion, in vivo skin permeation and deposition studies, and acute irritation studies were carried out. NPF was applied onto secondary thermal wounds manifested on mice models followed by macroscopic and histological examinations. Results: NPF had an average globule size of <75 nm. The viscosity was ~10 cP indicating the feasibility of expulsion from the container upon actuation. With no skin irritation, the foams showed a higher skin deposition of SD. A high contraction and an evident regeneration of the skin tissue upon treatment with NPF indicated a good recovery from the thermal injury was apparent from the histology studies. Conclusion: NPF represents an alternative topical formulation that can be employed as a safe and effective treatment modality for superficial second degree (partial thickness) burn wounds. With a minimal requirement of mechanical force, the no-touch application of NPF makes it suitable for sensitive and irritant skin surfaces. [ABSTRACT FROM AUTHOR]