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      Hybrid nanofilms as topical anesthetics for pain-free procedures in dentistry

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          Abstract

          Topical anesthetics are widely applied in order to relieve the discomfort and anxiety caused by needle insertion and other painful superficial interventions at the oral cavity. So far, there are no commercially available effective topical anesthetic formulations for that purpose, and the most of developments are related to hydrophilic and low mucoadhesive forms. Therefore, we have prepared different hybrid nanofilms composed of biopolymer matrices (chitosan, pectin, and chitosan-pectin) blended with nanostructured lipid carriers (NLC) loading the eutectic mixture of 5% lidocaine–prilocaine (LDC–PLC), in order to fulfill this gap in the market. These dual systems were processed as hybrid nanofilms by the solvent/casting method, and its mucoadhesive, structural and mechanical properties were detailed. The most appropriate hybrid nanofilm combined the advantages of both pectin (PCT) and NLC components. The resultant material presented sustained LDC–PLC release profile for more than 8 h; permeation across porcine buccal mucosa almost twice higher than control and non-cytotoxicity against 3T3 and HACAT cell lines. Then, the in vivo efficacy of PCT/NLC formulation was compared to biopolymer film and commercial drug, exhibiting the longest-lasting anesthetic effect (> 7 h), assessed by tail flick test in mice. These pectin-based hybrid nanofilms open perspectives for clinical trials and applications beyond Dentistry.

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          On the use of the Weibull function for the discernment of drug release mechanisms.

          Previous findings from our group based on Monte Carlo simulations indicated that Fickian drug release from Euclidian or fractal matrices can be described with the Weibull function. In this study, the entire drug release kinetics of various published data and experimental data from commercial or prepared controlled release formulations of diltiazem and diclofenac are analyzed using the Weibull function. The exponent of time b of the Weibull function is linearly related to the exponent n of the power law derived from the analysis of the first 60% of the release curves. The value of the exponent b is an indicator of the mechanism of transport of a drug through the polymer matrix. Estimates for b< or =0.75 indicate Fickian diffusion in either fractal or Euclidian spaces while a combined mechanism (Fickian diffusion and Case II transport) is associated with b values in the range 0.75
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            Buccal bioadhesive drug delivery--a promising option for orally less efficient drugs.

            Rapid developments in the field of molecular biology and gene technology resulted in generation of many macromolecular drugs including peptides, proteins, polysaccharides and nucleic acids in great number possessing superior pharmacological efficacy with site specificity and devoid of untoward and toxic effects. However, the main impediment for the oral delivery of these drugs as potential therapeutic agents is their extensive presystemic metabolism, instability in acidic environment resulting into inadequate and erratic oral absorption. Parenteral route of administration is the only established route that overcomes all these drawbacks associated with these orally less/inefficient drugs. But, these formulations are costly, have least patient compliance, require repeated administration, in addition to the other hazardous effects associated with this route. Over the last few decades' pharmaceutical scientists throughout the world are trying to explore transdermal and transmucosal routes as an alternative to injections. Among the various transmucosal sites available, mucosa of the buccal cavity was found to be the most convenient and easily accessible site for the delivery of therapeutic agents for both local and systemic delivery as retentive dosage forms, because it has expanse of smooth muscle which is relatively immobile, abundant vascularization, rapid recovery time after exposure to stress and the near absence of langerhans cells. Direct access to the systemic circulation through the internal jugular vein bypasses drugs from the hepatic first pass metabolism leading to high bioavailability. Further, these dosage forms are self-administrable, cheap and have superior patient compliance. Developing a dosage form with the optimum pharmacokinetics is a promising area for continued research as it is enormously important and intellectually challenging. With the right dosage form design, local environment of the mucosa can be controlled and manipulated in order to optimize the rate of drug dissolution and permeation. A rational approach to dosage form design requires a complete understanding of the physicochemical and biopharmaceutical properties of the drug and excipients. Advances in experimental and computational methodologies will be helpful in shortening the processing time from formulation design to clinical use. This paper aims to review the developments in the buccal adhesive drug delivery systems to provide basic principles to the young scientists, which will be useful to circumvent the difficulties associated with the formulation design.
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              In vitro evaluation of the mucoadhesive properties of chitosan microspheres

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                Author and article information

                Contributors
                nuneslica@gmail.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                9 July 2020
                9 July 2020
                2020
                : 10
                : 11341
                Affiliations
                [1 ]ISNI 0000 0001 0723 2494, GRID grid.411087.b, Department of Biochemistry and Tissue Biology, Institute of Biology, , University of Campinas - UNICAMP, ; Rua Monteiro Lobato, 255-Cidade Universitária, Campinas, São Paulo 13083862 Brazil
                [2 ]ISNI 0000 0001 0723 2494, GRID grid.411087.b, Department of Physiological Sciences, Piracicaba Dental School, , UNICAMP, ; Piracicaba, São Paulo Brazil
                [3 ]ISNI 0000 0001 2165 7632, GRID grid.411204.2, Department of Chemistry, , Federal University of Maranhão, ; São Luís, Maranhão Brazil
                [4 ]ISNI 0000 0001 0723 2494, GRID grid.411087.b, Department of Analytical Chemistry, Institute of Chemistry, , University of Campinas, UNICAMP, ; Campinas, São Paulo Brazil
                [5 ]ISNI 0000 0004 4647 6936, GRID grid.411284.a, School of Veterinary Medicine, Federal University of Uberlândia, UFU, ; Uberlândia, Minas Gerais Brazil
                Article
                68247
                10.1038/s41598-020-68247-0
                7347607
                16ba0c4a-d405-4f3c-919f-e158be70e5a2
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 30 March 2020
                : 22 June 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001807, Fundação de Amparo à Pesquisa do Estado de São Paulo;
                Award ID: 14/25372-0
                Award ID: 14/14457-5
                Award ID: 14/50867-3
                Categories
                Article
                Custom metadata
                © The Author(s) 2020

                Uncategorized
                materials science,nanoscience and technology
                Uncategorized
                materials science, nanoscience and technology

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