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PLGA (Lactic- co-glycolic acid) coated chitosan microspheres loaded with hydroxyapatite and doxycycline hyclate complex were developed in the present study for periodontal delivery. A modified single emulsion method was adopted for the development of microspheres. Formulation was optimized on the basis of particle size, drug loading and encapsulation efficiency with the central composite design using 2 3 factorial design. Microspheres were optimized and electron microscopy revealed their spherical shape and porous nature. In-vitro study showed initial burst and then sustained release behavior of the formulation for 14 days. Further, in-vitro antibacterial study performed on E. coli (ATCC-25922) and S. aureus (ATCC-29213) revealed concentration dependent activity. Also, in-vitro cyto-toxicity assessment ensures biocompatibility of the formulation with the fibroblast's cells. Overall, the quality by design assisted PLGA microspheres, demonstrated the desired attributes and were found suitable for periodontal drug delivery., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Eugenol is a bioactive compound widely available in many herbs like clove, cinnamon, tulsi, pepper etc. The compound is known for its antioxidant, antimicrobial, anesthetic, anti-inflammatory, neuroprotective, anti-diabetic, and anti-cancer activities. In pharmaceutical analysis, eugenol is used as a marker for single drugs and drug products. Dental care, household, and personal hygiene products are other areas where it has established its potential. In the food industry, eugenol is used as a flavouring agent in non-alcoholic beverages, baked foods, and chewing gums. Considering the huge potential of eugenol, this review is an attempt to collate the regulatory information, physico-chemical properties, toxicity profile, marketed conventional and novel formulations, analytical methods, extraction procedures, recent patents and clinical trials of the moiety. Based on literature survey a schematic diagram of mechanism of action has also been made., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Candidal vulvovaginitis (CVV), is the second most leading vaginal infection (global prevalence > 75%), caused due to excessive growth of Candida spp. , predominantly Candida albicans (>95% cases). The current treatment regimens for CVV are marred with the challenges of fungal resistance & infection recurrence, subsequently leading to the compromised therapeutic efficacy of anti-fungal drugs, prolonged treatment and low patient compliance. The core of the present research was the fabrication & investigation of 2 T-SLN (solid lipid nanoparticles) gel carrying luliconazole for the amelioration of CVV. '2T' symbolizes transvaginal & thermosensitive attributes of the present formulation. SLNs were prepared by a modified melt emulsification-ultra sonication method using a combination of solid lipids (Gelucire 50/13 & Precirol ATO 5), surfactant (Tween 80) and co-surfactant (Kolliphor). Formulation by design (FbD) approach was adopted to obtain appropriately screened and tailored SLNs. The optimized SLNs yielded a particle size, polydispersity index & entrapment efficiency of 62.18 nm, 0.263 & 81.5% respectively. To formulate the 2 T-gel, the final SLNs were loaded into Carbopol 971P-NF and Triethanolamine based gel. The 2 T-SLN gel was found to be easily spreadable and homogenous with mean extrudability (15 ± 0.4 g/cm 2 ), viscosity (696.42 ± 2.34 Pa·s) and %drug content (93.24 ± 0.73%) values.. The pH of the prepared 2 T-SLN gel (4.5 ± 0.5) was in concordance with the vaginal pH (normal conditions). For in-vitro characterization of an optimized 2 T-SLN gel the release kinetics & anticandidal activity were assessed which offers a %cumulative drug release of 62 ± 0.5% in 72 h and 37.3 ± 1.5 mm zone of inhibition in 48 h. The visual appearance & dimensions were determined using fluorescent microscopy (spherical shape) & transmission electron microscopy (90-120 nm) respectively. The optimized 2 T-SLN gel showcases a skin-friendly profile with no significant signs of erythema and oedema and was found to be stable at room temperature for 2 months without any visual non-uniformity/cracking/breaking. In conclusion, the current research serves a new therapeutic perspective in assessing the activity of luliconazole for vaginal drug delivery using a 2 T-SLN gel system., (© 2020 The Authors.)

In the current work, we set out to develop and evaluate a gingiva disc of cellulose acetate phthalate and poloxamer F-127 for the simultaneous delivery of multiple drugs, namely minocycline, celecoxib, doxycycline hyclate, and simvastatin, to abolish infection, impede inflammation, avert collagen destruction, and promote alveolar bone regeneration, respectively. In vitro release studies revealed the sustained release profiles of the drugs for 12 h and that they were active against Staphylococcus aureus , Escherichia coli and Streptococcus mutans. The in vivo bioactivity levels of these drugs were assessed by comparing the number of colony forming units during different phases of a study on Wistar rats, and the results showed a reduction in the number of bacterial colonies with the applied formulation. A mucosal irritation study conducted on Wistar rat gingiva confirmed the non-irritancy of the optimal gingiva disc. Hence, this customized, non-invasive polymeric gingiva disc displaying a sustained release of drugs can be a useful tool to treat acute to moderate stages of periodontitis., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Melanoma is one of the most aggressive cancers which has very low response rate and survival rate. Melanoma cells are known to be inherently resistant to the chemotherapy which results in poor outcomes and even failure of the therapy. For this reason, a better understanding of underlying mechanism of melanoma pathogenesis and resistance is required, so that more efficient and novel therapeutic strategies can be developed. Survivin is a protein which is overexpressed in melanoma cells and is known to impart resistance to them against apoptosis. Also, melanoma cells overexpress Vascular Endothelial Growth Factor (VEGF) and basic Fibroblast Growth Factor (bFGF) angiogenic growth factors which lead to aggressive angiogenesis in melanoma cells thereby making the treatment more challenging. This hypothesis presents a combinatorial approach against melanoma where an anti-survivin agent and an anti-angiogenic agent are combined with a chemotherapeutic drug and loaded in surface functionalized liposomes in order to target specific mechanisms of melanoma, thus overcoming its resistance. Thus, the study aims to overcome the resistance of melanoma cells by developing a wise combination of drugs and achieve a higher response rate in resistant melanoma model, which is usually not achieved with the existing treatment modalities., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Rutin (RT), an antioxidant drug, has been utilized to treat cerebral ischemia hence a sensitive quantification method for estimation of RT in brain homogenate is necessary to develop. This study aims to prepare RT loaded Chitosan Nanoparticles (RT-CS-NPs) develop and validate ultra-high performance liquid chromatography-electrospray ionization-synapt mass spectrometric method Synapt Mass Spectrometry (Synapt MS) (UHPLC/ESI-QTOF-MS/MS) for quantification of RT in brain homogenate from Wistar rat. The process of chromatographic separation was carried out on Waters ACQUITY UPLC™ with the components of separation in detail as; column: BEH C-18 with dimension as 2.1 mm×100 mm and particle size 1.7 µm, mobile phase: acetonitrile (85 % v/v/v): 2 mM ammonium formate (15 % v/v/v): formic acid (0.1 % v/v/v) and flow rate: 0.25 mL/min. Liquid-liquid extraction method (LLE), in mixture, i.e. ethyl acetate:acetonitrile, was considered to optimize the recovery of analyte from the brain homogenate of Wistar rat. Over a total run time of 5 minutes, the elution time for RT and internal standard (IS), i.e. Tolbutamide, observed was 2.67 and 2.82 min respectively whereas the transition observed for RT and IS was at m/z 611.1023/303.1071 and 271.1263/155.1073, respectively. Results, regarding various processes and parameters studied for RT as summarized, established a linear dynamic range over a concentration range of 1.00 ng/mL - 1000.0 ng/mL with r 2 ; 0.9991±0.0010. Accuracy for intra and inter-assay in terms of % CV revealed a range of 0.45- 2.11 whereas lower limit of detection (LOD) and quantitation (LOQ) observed was 0.09 ng/mL and 0.142 ng/mL, respectively. The analyte stability as well as method specificity and accuracy, i.e. recovery > 86 %, supports the idea for application of current developed method in order to quantify and evaluate the RT-loaded-CS-NPs for RT determination in brain homogenate after intranasal drug delivery.

The pivotal idea toward the development of chronotherapeutics is synchronizing the in vivo drug bioavailability with the rhythms of the disease to optimize therapeutic outcomes and minimize side effects, which is contrary to the homeostatic theory of drug delivery. The advent of formulation technologies, marketing exclusivities of innovative products, and provisions/amendments in regulatory frameworks have led to the development of commercial chronotherapeutic products, but their numbers are few and are confined mainly to diseases of the cardiovascular system. A major bottleneck for its development would be the understanding of rhythmic variations of disease, but following regulatory pathways for commercial development has always been challenging. In this article, a few commercial products have been investigated in view of their developmental strategies in order to find out the minimum preclinical and clinical studies needed for the development of chronotherapeutics.

The aim of the work was to develop, characterize, and carry out a clinical trial with nano-atropine sulfate (nano-AS) dry powder inhaler (DPI), because this route may offer several advantages over the conventional intramuscular route as an emergency treatment, including ease of administration and more rapid bioavailability. Different batches of nanoparticles of AS were produced using variants of nanoprecipitation method. The influence of the process parameters, such as the types and quantity of solvent and nonsolvent, the stirring speed, the solvent-to-nonsolvent volume ratio, and the drug concentration, was investigated. The methodology resulted in optimally sized particles. Bulk properties of the particles made by the chosen methodology were evaluated. A clinical trial was conducted in six healthy individuals using a single DPI capsule containing 6 mg nano-AS DPI in lactose. Early blood bioavailability and atropinization pattern confirmed its value as a potential replacement to parenteral atropine in field conditions. The formulation seems to have the advantage of early therapeutic drug concentration in blood due to absorption through the lungs as well as sustained action due to absorption from the gut of the remaining portion of the drug.

The recognition of periodontal diseases as amenable to local antibiotherapy has resulted in a paradigmatic shift in treatment modalities of dental afflictions. Moreover the presence of antimicrobial resistance, surfacing of untoward reactions owing to systemic consumption of antibiotics has further advocated the use of local delivery of physiologically active substances into the periodontal pocket. While antimicrobials polymerized into acrylic strips, incorporated into biodegradable collagen and hollow permeable cellulose acetate fibers, multiparticulate systems, bio-absorbable dental materials, biodegradable gels/ointments, injectables, mucoadhesive microcapsules and nanospheres will be more amenable for direct placement into the periodontal pockets the lozenges, buccoadhesive tablets, discs or gels could be effectively used to mitigate the overall gingival inflammation. Whilst effecting controlled local delivery of a few milligram of an antibacterial agent within the gingival crevicular fluid for a longer period of time, maintaining therapeutic concentrations such delivery devices will circumvent all adverse effects to non- oral sites. Since the pioneering efforts of Goodson and Lindhe in 1989, delivery at gingival and subgingival sites has witnessed a considerable progress. The interest in locally active systems is evident from the patents being filed and granted. The present article shall dwell in reviewing the recent approaches being proffered in the field. Patents as by Shefer, et al. US patent, 6589562 dealing with multicomponent biodegradable bioadhesive controlled release system for oral care products, Lee, et al. 2001, US patent 6193994, encompassing a locally administrable, biodegradable and sustained-release pharmaceutical composition for periodontitis and process for preparation thereof and method of treating periodontal disease as suggested by Basara in 2004via US patent 6830757, shall be the types of intellectual property reviewed and presented in the current manuscript.

Multiple emulsions are complex polydispersed systems where both oil in water and water in oil emulsion exists simultaneously which are stabilized by lipophillic and hydrophilic surfactants respectively. The ratio of these surfactants is important in achieving stable multiple emulsions. Among water-in-oil-in-water (w/o/w) and oil-in-water-in-oil (o/w/o) type multiple emulsions, the former has wider areas of application and hence are studied in great detail. Formulation, preparation techniques and in vitro characterization methods for multiple emulsions are reviewed. Various factors affecting the stability of multiple emulsions and the stabilization approaches with specific reference to w/o/w type multiple emulsions are discussed in detail. Favorable drug release mechanisms and/or rate along with in vivo fate of multiple emulsions make them a versatile carrier. It finds wide range of applications in controlled or sustained drug delivery, targeted delivery, taste masking, bioavailability enhancement, enzyme immobilization, etc. Multiple emulsions have also been employed as intermediate step in the microencapsulation process and are the systems of increasing interest for the oral delivery of hydrophilic drugs, which are unstable in gastrointestinal tract like proteins and peptides. With the advancement in techniques for preparation, stabilization and rheological characterization of multiple emulsions, it will be able to provide a novel carrier system for drugs, cosmetics and pharmaceutical agents. In this review, emphasis is laid down on formulation, stabilization techniques and potential applications of multiple emulsion system.