Papers by Michelle Franz-Montan
O objetivo deste estudo cruzado e cego foi avaliar a eficacia da anestesia topica de ropivacaina ... more O objetivo deste estudo cruzado e cego foi avaliar a eficacia da anestesia topica de ropivacaina a 1% (forma lipossomada ou nao) em Odontologia. Trinta voluntarios foram submetidos a anestesia topica com quatro anestesicos, em oito sessoes (tratamentos) determinadas aleatoriamente: 20mg de gel de ropivacaina a 1% -Ropi-20, 60mg de gel de ropivacaina a 1% -Ropi-60, 20mg de gel de ropivacaina a 1% encapsulada em lipossomas -RopiLipo-20, 60mg de gel de ropivacaina a 1% encapsulada em lipossomas -RopiLipo-60, 20mg da mistura eutetica de lidocaina a 2.5% e prilocaina a 2.5% (EMLA cream AstraZeneca®) - EMLA-20, 60mg de EMLA cream -EMLA-60, 20mg de gel de benzocaina a 20% (Benzotop® DFL) -Benzo-20 e 60mg de gel de benzocaina a 20% -Benzo-60. Cada tratamento foi aplicado no fundo de sulco da regiao de canino superior direito durante dois minutos; o intervalo entre os tratamentos foi de uma semana. Foram avaliadas a anestesia pulpar, por meio de estimulo eletrico (pulp tester); a dor durante a puncao por meio das escalas analogica visual (EAV) e de 11 pontos em caixa (E11); e a anestesia em tecido mole por meio de estimulo fisico. A influencia do anestesico na resposta pulpar foi avaliada durante 20 minutos apos a aplicacao do anestesico topico. Nao houve diferenca estatisticamente significante entre os tratamentos com relacao as escalas EAV e E11 (p>0.05). A duracao da anestesia em tecido mole com o EMLA-60 e RopiLipo-60 foi maior (p 0.05). Nenhum dos tratamentos avaliados exerceu efeito anestesico sobre o tecido pulpar. Assim, a ropivacaina a 1% encapsulada ou nao em lipossomas apresentaram eficacia semelhante em reduzir a dor a puncao em comparacao aos outros anestesicos avaliados, no entanto, nas condicoes avaliadas, nenhum dos anestesicos exerceu influencia sobre a resposta pulpar
Pharmaceutics, 2021
Permeation assays are important for the development of topical formulations applied on buccal muc... more Permeation assays are important for the development of topical formulations applied on buccal mucosa. Swine buccal and esophageal epithelia are usually used as barriers for these assays, while frozen epithelia have been used to optimize the experimental setup. However, there is no consensus on these methods. In transdermal studies, barrier integrity has been evaluated by measuring electrical resistance (ER) across the skin, which has been demonstrated to be a simple, fast, safe, and cost-effective method. Therefore, the aims here were to investigate whether ER might also be an effective method to evaluate buccal and esophageal epithelium mucosa integrity for in vitro permeation studies, and to establish a cut-off ER value for each epithelium mucosa model. We further investigated whether buccal epithelium could be substituted by esophageal epithelium in transbuccal permeation studies, and whether their permeability and integrity were affected by freezing at −20 °C for 3 weeks. Fresh ...
COMPOSICcO PHARMACEUTICAL, PROCESS OF OBTENCcO COMPOSICcO PHARMACEUTICAL USE OF A pharmaceuticall... more COMPOSICcO PHARMACEUTICAL, PROCESS OF OBTENCcO COMPOSICcO PHARMACEUTICAL USE OF A pharmaceutically effective amount of anesthesia and gelling agent, PRODUCT AND TREATMENT METHOD. The present invention relates to a pharmaceutical composition for local anesthetic gel directed to topical use in dental procedures. A pharmaceutical composition comprising a pharmaceutically effective amount of at least one anesthetic and at least one gelling agent, wherein said composition has a viscosity of 30 Pa.s, when subjected to a temperature variation of 5 ° C to 50 ° C. The presented invention allows greater penetration of the anesthetic at a stable viscosity that keeps the drug for longer and at higher concentration at the site of action, increased anesthesia time, reducing their toxicity and by restricting the action of the drug to the site of application.
Pharmaceutics, 2021
Recent advances have been reported for needle-free local anesthesia in maxillary teeth by adminis... more Recent advances have been reported for needle-free local anesthesia in maxillary teeth by administering a nasal spray of tetracaine (TTC) and oxymetazoline, without causing pain, fear, and stress. This work aimed to assess whether a TTC-loaded hybrid system could reduce cytotoxicity, promote sustained permeation, and increase the anesthetic efficacy of TTC for safe, effective, painless, and prolonged analgesia of the maxillary teeth in dental procedures. The hybrid system based on TTC (4%) encapsulated in nanostructured lipid carriers (NLC) and incorporated into a thermoreversible hydrogel of poloxamer 407 (TTCNLC-HG4%) displayed desirable rheological, mechanical, and mucoadhesive properties for topical application in the nasal cavity. Compared to control formulations, the use of TTCNLC-HG4% slowed in vitro permeation of the anesthetic across the nasal mucosa, maintained cytotoxicity against neuroblastoma cells, and provided a three-fold increase in analgesia duration, as observed u...
Scientific Reports, 2020
Topical anesthetics are widely applied in order to relieve the discomfort and anxiety caused by n... more 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...
International Journal of Molecular Sciences, 2020
Acidic environments, such as in inflamed tissues, favor the charged form of local anesthetics (LA... more Acidic environments, such as in inflamed tissues, favor the charged form of local anesthetics (LA). Hence, these drugs show less cell permeation and diminished potency. Since the analgesic capsaicin (CAP) triggers opening of the TRPV1 receptor pore, its combination with LAs could result in better uptake and improved anesthesia. We tested the above hypothesis and report here for the first time the analgesia effect of a two-drug combination (LA and CAP) on an inflamed tissue. First, CAP solubility increased up to 20 times with hydroxypropyl-beta-cyclodextrin (HP-β-CD), as shown by the phase solubility study. The resulting complex (HP-β-CD-CAP) showed 1:1 stoichiometry and high association constant, according to phase-solubility diagrams and isothermal titration calorimetry data. The inclusion complex formation was also confirmed and characterized by differential scanning calorimetry (DSC), X-ray diffraction, and 1H-NMR. The freeze-dried complex showed physicochemical stability for at ...
Journal of Pharmacy and Pharmacology, 2019
Objectives To evaluate whether a ternary system composed of hydroxypropyl-β-cyclodextrin (HP-βCD)... more Objectives To evaluate whether a ternary system composed of hydroxypropyl-β-cyclodextrin (HP-βCD) further encapsulated into egg phosphatidylcholine liposomes (LUV) could prolong the action and reduce the toxicity of ropivacaine (RVC). Methods Dynamic light scattering and NMR were used to characterize the inclusion complex (RVC : HP-βCD), liposomal (RVC : LUV) and ternary (LUV : RVC : HP-βCD) systems containing 0.25% RVC. Their encapsulation efficiency, release kinetics, in-vitro cytotoxicity and in-vivo anaesthetic effect (paw-withdraw tests in mice) were also evaluated. Key findings 1 : 1 RVC : HP-βCD inclusion complex was encapsulated in liposomes (220.2 ± 20.3 nm size, polydispersity <0.25, zeta potentials = −31.7 ± 1.4 mV). NMR (diffusion-ordered spectroscopy (DOSY)) revealed stronger anaesthetic binding to LUV : RVC : HP-βCD (Ka = 342 m−1) than to RVC : HP-βCD (Ka = 128 m−1) or liposomal formulation (Ka = 22 m−1). The formulations promoted in-vitro sustained drug release and...
International Journal of Polymer Science, 2017
The use of biomaterials composed of organic pristine components has been successfully described i... more The use of biomaterials composed of organic pristine components has been successfully described in several purposes, such as tissue engineering and drug delivery. Drug delivery systems (DDS) have shown several advantages over traditional drug therapy, such as greater therapeutic efficacy, prolonged delivery profile, and reduced drug toxicity, as evidenced by in vitro and in vivo studies as well as clinical trials. Despite that, there is no perfect delivery carrier, and issues such as undesirable viscosity and physicochemical stability or inability to efficiently encapsulate hydrophilic/hydrophobic molecules still persist, limiting DDS applications. To overcome that, biohybrid systems, originating from the synergistic assembly of polymers and other organic materials such as proteins and lipids, have recently been described, yielding molecularly planned biohybrid systems that are able to optimize structures to easily interact with the targets. This work revised the biohybrid DDS clari...
Frontiers in Pharmacology, 2019
Oral diseases, Jan 15, 2018
To determine whether stress-related substances and sex hormones influence the growth and in vitro... more To determine whether stress-related substances and sex hormones influence the growth and in vitro production of volatile sulfur compounds (VSCs) by Solobacterium moorei and Fusobacterium nucleatum. Bacteria growth and VSCs production were evaluated in the presence of alpha-amylase, beta-defensin-2, mucin, estradiol, and progesterone. Growth was evaluated by colony counting, and the production of the VSCs hydrogen sulfide (H S) and methyl mercaptan (CH SH) was measured using the Oral Chroma™ instrument. Mucin induced the production of H S by both bacteria, but had a slight inhibitory effect on CH SH production by F. nucleatum. It also increased the viability of F. nucleatum. Alpha-amylase increased H S production by S. moorei and CH SH production by F. nucleatum, but had no effect on H S production by F. nucleatum. No substance altered the viability of S. moorei. No effects of beta-defensin-2, estradiol, or progesterone were observed. The salivary stress-related proteins mucin and al...
Journal of nanoscience and nanotechnology, 2018
This work describes the development of poly-ε-caprolactone nanocapsules (PCL-NC) and solid lipid ... more This work describes the development of poly-ε-caprolactone nanocapsules (PCL-NC) and solid lipid nanoparticles (SLN) aiming delivery for articaine (ATC), in order to improve its chemical stability in semi-solid preparations looking forward their use for skin delivery. The nanoparticles were characterized by size, polydispersity index, and pH. Cellular viability was evaluated using the MTT test and the in vitro release kinetics was determined using a two-compartment model. The hydrogels with nanoparticle suspensions were characterized considering their rheological aspects and in vitro permeation across artificial membranes. Colloidal stability was satisfactory, since the formulations did not present major alterations during 120 days. High ATC encapsulation was achieved (78% for PCL-NC and 65% for SLN). The release profile of PCL-NC-ATC was slower, compared to the free molecule and SLN-ATC. MTT experiments showed the nanosystems were capable to increase cellular viability compared wit...
Current pharmaceutical design, Jan 21, 2017
Topical drug administration offers an attractive route with minimal invasiveness. It also avoids ... more Topical drug administration offers an attractive route with minimal invasiveness. It also avoids limitations of intravenous administration such as the first pass metabolism and presystemic elimination within the gastrointestinal tract. Furthermore, topical drug administration is safe, have few side effects, is easy to apply, and offers a fast onset of action. However, the development of effective topical formulations still represents a challenge for the desired effect to be reached, locally or systemically. Solid lipid nanoparticles and nanostructured lipid carriers are particular candidates to overcome the problem of topical drug administration. The nanometric particle size of lipid nanoparticles favors the physical adhesion to the skin or mucosal, what can also be attained with the formation of hybrid (nanoparticles/polymer) systems. In this review, we discuss the major challenges for lipid nanoparticles formulations for topical application to oral mucosa, skin, and eye, highlight...
Clinical Therapeutics, 2017
The Journal of pharmacy and pharmacology, Jan 17, 2017
Oxethazaine (OXZ) is one of the few local anaesthetics that provides analgesia at low pH, but pre... more Oxethazaine (OXZ) is one of the few local anaesthetics that provides analgesia at low pH, but presents poor solubility, cytotoxicity and no parenteral formulations. To address these issues, we aimed to prepare OXZ host-guest inclusion complex with hydroxypropyl-beta-cyclodextrin (HP-β-CD). The inclusion complex was formed by co-solubilization, followed by a job plot analysis to determine stoichiometry of complexation and dialysis equilibrium analysis (based on UV/VIS absorption and fluorescence profiles of OXZ). Complex formation was confirmed by phase-solubility data, X-ray, Scanning Electron Microscopy and DOSY-(1) H-NMR experiments. In vitro cytotoxicity was analysed by MTT test in 3T3 fibroblasts. In vivo analgesia was tested by Von Frey test (inflammatory wounds - rats). Oxethazaine complexed (1 : 1 molar ratio) with HP-β-CD, as indicated by loss of OZX crystalline structure (X-ray) and strong host: guest interaction (NMR, K = 198/M), besides increased solubility. In vitro cell...
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, Jan 11, 2016
The objective of this study was to determine whether in buccal tissues, after insertion and remov... more The objective of this study was to determine whether in buccal tissues, after insertion and removal of coated microneedles, the presence of saliva over the insertion site can lead to loss of the deposited drug, and if saliva can influence in vitro permeation of the drug across the tissue. Microneedles were coated with sulforhodamine (SRD), which was used as a model drug, and inserted in to porcine buccal mucosa in vitro. Fluorescence microscopy was used to study microneedle coating quality and the diffusion of SRD through the mucosa. Permeation experiments were conducted for simulated dynamic or static salivary flow by adding 100μL/h or 100, 200 or 300μL of phosphate buffered saline (PBS) in the donor compartment of the Franz diffusion cells, into which buccal tissue after insertion of SRD-coated microneedles was placed. Microscopy showed that microneedles were uniformly coated with SRD and that SRD was successfully delivered in to the mucosa. Some SRD remained in the tissue even af...
Journal of liposome research, Jan 28, 2016
The aim of this study was to evaluate the in vitro cytotoxicity and the in vivo analgesic effect ... more The aim of this study was to evaluate the in vitro cytotoxicity and the in vivo analgesic effect and local toxicity of the local anesthetic butamben (BTB) encapsulated in conventional or elastic liposomes incorporated in gel formulations. The results showed that both gel formulations of liposomal BTB reduced the cytotoxicity (p < 0.001; one-way ANOVA/Tukey's test) and increased the topical analgesic effect (p < 0.05; one-way ANOVA/Tukey's test) of butamben, compared to plain BTB gel. The gel formulations presented good rheological properties, and stability assays detected no differences in physicochemical stability up to 30 d after preparation. Moreover, histological assessment revealed no morphological changes in rat skin after application of any of the gel formulations tested.
Objectives: The aim of this study was to develop a suitable in vitro condition simulating saliva ... more Objectives: The aim of this study was to develop a suitable in vitro condition simulating saliva to perform permeation studies involving coated microneedles across pig oral mucosa in Franz diffusion cells. Methods: Sulforhodamine, a fluorescent modeldrug, was coated on metal microneedles using a microprecision coating technique and efficiency and quality of coating was evaluated. Porcine buccal mucosa was submitted to a 3minapplication of coatedmicroneedles to: confirm mucosal perforation by histological analyses; evaluate the efficiency of delivery; and conduct permeation studies. Permeation was performed in Franztype diffusion cells during 24hours. Influence of saliva in removal of penetrateddrug was assessed in the donor chamber by using 3 different volumes of PBS (100, 200 and 300µL) over the tissue throughout the experiment. These groups were compared to either a " moist condition " with no PBS in contact to the tissue (moist gauze) and a control group not su...
Journal of Liposome Research, 2015
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Papers by Michelle Franz-Montan