Analgesic Effect of Sulforaphane: A New Application for Poloxamer-Hyaluronic Acid Hydrogels Juliana Zampoli Boava Papini, Bruno de Assis Esteves, Vagner Gomes de Souza Oliveira, Henrique Ballassani Abdalla, Cintia Maria Saia Cereda, et al. Gels, 2024 Sulforaphane (SFN) has shown potential as an antioxidant and anti-inflammatory agent. To improve its druggability, we developed new analgesic formulations with sulforaphane-loaded hyaluronic acid (HA)-poloxamer (PL) hydrogel. This study evaluated the pre-clinical safety and effectiveness of these formulations. Effectiveness was tested on Wistar rats divided into groups (n = 15) receiving (IM, 10 mg/kg) SFN formulations or control groups (without SFN). This study used a hind paw incision postoperative pain model to evaluate mechanical hypersensitivity with von Frey filaments. TNF-α, IL-1β, substance P, and CGRP levels verified anti-inflammatory activity in the hind paw tissue. Histopathology of tissues surrounding the injection site was assessed after 2 and 7 days post-treatment. To corroborate drug safety, cell viability of 3T3 and RAW 264.7 cultures was assessed. Additionally, RAW 264.7 cultures primed with carrageenan evaluated nitric oxide (NO) levels. All animals exhibited post-incisional hypersensitivity, and F2 (PL 407/338 (18/2%) + HA 1% + SFN 0.1%) showed a longer analgesic effect (p < 0.05). F2 reduced TNF-α, IL-1β, and CGRP levels (p < 0.05). Histopathological evaluation showed mild to moderate inflammatory reactions after the formulations’ injections. F2 produced no significant difference in cell viability (p > 0.05) but reduced NO production (p < 0.05). Thus, our results highlight the biocompatibility and effectiveness of F2.
Monoketonic Curcuminoid-Lidocaine Co-Deliver Using Thermosensitive Organogels: From Drug Synthesis to Epidermis Structural Studies Aryane A. Vigato, Ian P. Machado, Matheus del Valle, Patricia A. da Ana, Anderson F. Sepulveda, et al. Pharmaceutics, 2022 Organogels (ORGs) are remarkable matrices due to their versatile chemical composition and straightforward preparation. This study proposes the development of ORGs as dual drug-carrier systems, considering the application of synthetic monoketonic curcuminoid (m-CUR) and lidocaine (LDC) to treat topical inflammatory lesions. The monoketone curcuminoid (m-CUR) was synthesized by using an innovative method via a NbCl5–acid catalysis. ORGs were prepared by associating an aqueous phase composed of Pluronic F127 and LDC hydrochloride with an organic phase comprising isopropyl myristate (IPM), soy lecithin (LEC), and the synthesized m-CUR. Physicochemical characterization was performed to evaluate the influence of the organic phase on the ORGs supramolecular organization, permeation profiles, cytotoxicity, and epidermis structural characteristics. The physico-chemical properties of the ORGs were shown to be strongly dependent on the oil phase constitution. Results revealed that the incorporation of LEC and m-CUR shifted the sol-gel transition temperature, and that the addition of LDC enhanced the rheological G′/G″ ratio to higher values compared to original ORGs. Consequently, highly structured gels lead to gradual and controlled LDC permeation profiles from the ORG formulations. Porcine ear skin epidermis was treated with ORGs and evaluated by infrared spectroscopy (FTIR), where the stratum corneum lipids were shown to transition from a hexagonal to a liquid crystal phase. Quantitative optical coherence tomography (OCT) analysis revealed that LEC and m-CUR additives modify skin structuring. Data from this study pointed ORGs as promising formulations for skin-delivery.
Ropivacaine-Loaded Poloxamer Binary Hydrogels for Prolonged Regional Anesthesia: Structural Aspects, Biocompatibility, and Pharmacological Evaluation Kelli Cristina Freitas Mariano, Juliana Zampoli Boava Papini, Naially Cardoso de Faria, Daniele Nicoli Cabral Heluany, Ana Luiza Lourençoni Botega, et al. Biomed Research International, 2021 This study reports the development of thermosensitive hydrogels for delivering ropivacaine (RVC), a wide clinically used local anesthetic. For this purpose, poloxamer‐ (PL‐) based hydrogels were synthesized for evaluating the influence of polymer concentration, hydrophilic‐lipophilic balances, and binary system formation on biopharmaceutical properties and pharmacological performance. Transition temperatures were shifted, and rheological analysis revealed a viscoelastic behavior with enhanced elastic/viscous modulus relationship (G’/G” = 1.8 to 22 times), according to hydrogel composition and RVC incorporation. The RVC release from PL407 and PL407/338 systems followed the Higuchi model (R2 = 0.923–0.989), indicating the drug diffusion from hydrogels to the medium. RVC‐PL hydrogels were potentially biocompatible evoking low cytotoxic effects (in fibroblasts and Schwann cells) and mild/moderate inflammation signs on sciatic nerve nearby histological evaluation. In vivo pharmacological assays demonstrated that PL407 and PL407/338 evoked differential analgesic effects, by prolonging the sensory blockade duration up to ~340 and 250 min., respectively. All those results highlighted PL407 and PL407/338 as promising new strategies for sustaining analgesic effects during the postoperative period.
Improved efficacy of naproxen-loaded NLC for temporomandibular joint administration Viviane A. Guilherme, Lígia N. M. Ribeiro, Ana C. S. Alcântara, Simone R. Castro, Gustavo H. Rodrigues da Silva, et al. Scientific Reports, 2019 Inflammatory conditions of the temporomandibular joint (TMJ) and peripheral tissues affect many people around the world and are commonly treated with non-steroidal anti-inflammatory drugs (NSAIDs). However, in order to get desirable results, treatments with NSAIDs may take weeks, causing undesirable side effects and requiring repeated administration. In this sense, this work describes the development of an optimized nanostructured lipid carrier (NLC) formulation for intra-articular administration of naproxen (NPX). An experimental design (23) selected the best formulation in terms of its physicochemical and structural properties, elucidated by different methods (DLS, NTA, TEM, DSC, and ATR-FTIR). The chosen formulation (NLC-NPX) was tested on acute inflammatory TMJ nociception, in a rat model. The optimized excipients composition provided higher NPX encapsulation efficiency (99.8%) and the nanoparticles were found stable during 1 year of storage at 25 °C. In vivo results demonstrated that the sustained delivery of NPX directly in the TMJ significantly reduced leukocytes migration and levels of pro-inflammatory cytokines (IL-1β and TNF-α), for more than a week. These results point out the NLC-NPX formulation as a promising candidate for the safe treatment of inflammatory pain conditions of TMJ or other joints.
Preclinical Evaluation of Ropivacaine in 2 Liposomal Modified Systems Carolina C. Rennó, Juliana Z. B. Papini, Cintia Maria Saia Cereda, Elizabeth Martinez, Victor Angelo Montalli, et al. Anesthesia and Analgesia, 2019 BACKGROUND: Our research group has recently developed liposomes with ionic gradient and in a combined manner as donor and acceptor vesicles containing ropivacaine (RVC; at 2% or 0.75%). Looking for applications of such novel formulations for postoperative pain control, we evaluated the duration of anesthesia, pharmacokinetics, and tissue reaction evoked by these new RVC formulations. METHODS: The formulations used in this study were large multivesicular vesicle (LMVV) containing sodium acetate buffer at pH 5.5 or in a combined manner with LMVV as donor and large unilamellar vesicles (LUVs) as acceptor vesicles with an external pH of 7.4. Wistar rats were divided into 6 groups (n = 6) and received sciatic nerve block (0.4 mL) with 6 formulations of RVC (LMVVRVC0.75%, LMVV/LUVRVC0.75%, LMVVRVC2%, LMVV/LUVRVC2%, RVC 0.75%, and RVC 2%). To verify the anesthetic effect, the animals were submitted to the pain pressure test and the motor block was also monitored. Histopathology of the tissues surrounding the sciatic nerve region was also assessed 2 and 7 days after treatment. Rats (n = 6) were submitted to a hind paw incision, and mechanical hypersensitivity was measured via the withdrawal response using von Frey filaments after injection of the 6 formulations. Finally, New Zealand white rabbits (n = 6) received sciatic nerve block (3 mL) with 1 of the 6 formulations of RVC. Blood samples were collected predose (0 minutes) and at 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 420, 480, and 540 minutes after injection. RVC plasma levels were determined using a triple-stage quadrupole mass spectrometer. RESULTS: Duration and intensity of the sensory block were longer with all liposomal formulations, when compared to the plain RVC solution (P < .05). Histopathological evaluation showed greater toxicity for the positive control (lidocaine 10%), when compared to all formulations (P < .05). After the hind paw incision, all animals presented postincisional hypersensitivity and liposomal formulations showed longer analgesia (P < .05). LMVVRVC0.75% presented higher time to reach maximum concentration and mean residence time than the remaining formulations with RVC 0.75% (P < .05), so LMVV was able to reduce systemic exposure of RVC due to slow release from this liposomal system. CONCLUSIONS: All new liposomal formulations containing 0.75% RVC were able to change the pharmacokinetics and enhance anesthesia duration due to slow release of RVC from liposomes without inducing significant toxic effects to local tissues.
Drug delivery systems for local anesthetics Eneida de Paula, Cintia Cereda, Giovana Tofoli, Michelle Franz-Montan, Leonardo Fraceto, et al. Recent Patents on Drug Delivery and Formulation, 2010
Bioadhesive film for the delivery of local anesthetics to the buccal mucosa: ex-vivo and in-vivo evaluation GR Tofoli, JZB Papini, B Furlan, CMS Cereda, SA Calafatti, E De Paula, ... Journal of Drug Delivery Science and Technology 103, 106446 , 2025 2025 Citations: 2
Influence of structural organization on mucoadhesive properties of poloxamer-hyaluronic acid-based micelles and hydrogels: From molecular modelling to biointerfaces interactions AF Sepulveda, JB da Silva, ML Bruschi, MKKD Franco, F Yokaichiya, ... Colloids and Surfaces A: Physicochemical and Engineering Aspects 698, 134527 , 2024 2024 Citations: 4
Analgesic effect of sulforaphane: a new application for poloxamer-hyaluronic acid hydrogels JZB Papini, B de Assis Esteves, VG de Souza Oliveira, HB Abdalla, ... Gels 10 (7), 460 , 2024 2024 Citations: 7
Bioadhesive film for the delivery of local anesthetics to the buccal mucosa: ex-vivo and in-vivo evaluation GR Tofoli, JZB Papini, B Furlan, CMS Cereda, SA Calafatti, E de Paula, ... JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY 103, 10 , 2024 2024
Nanomedicine Applied to Inflammatory Bowel Diseases CMS Cereda, GR Tofoli Biotechnology Applied to Inflammatory Diseases: Cellular Mechanisms and … , 2023 2023
Monoketonic curcuminoid-lidocaine co-deliver using thermosensitive organogels: From drug synthesis to epidermis structural studies AA Vigato, IP Machado, M Del Valle, PA da Ana, AF Sepulveda, ... Pharmaceutics 14 (2), 293 , 2022 2022 Citations: 16
Pre-clinical evaluation of new dibucaine formulations for preventive analgesia B Furlan, BT De Melo, JZB Papini, M Sperandio, JD Oliveira, E De Paula, ... Journal of liposome research 31 (3), 230-236 , 2021 2021 Citations: 4
Ropivacaine‐Loaded Poloxamer Binary Hydrogels for Prolonged Regional Anesthesia: Structural Aspects, Biocompatibility, and Pharmacological Evaluation KCF Mariano, JZB Papini, NC de Faria, DNC Heluany, ALL Botega, ... BioMed Research International 2021 (1), 7300098 , 2021 2021 Citations: 6
Evaluation of Budesonide–Hydroxypropyl- β -Cyclodextrin Inclusion Complex in Thermoreversible Gels for Ulcerative Colitis CM Lázaro, CC de Oliveira, A Gambero, T Rocha, CMS Cereda, ... Digestive diseases and sciences 65 (11), 3297-3304 , 2020 2020 Citations: 20
Evaluation of Budesonide-hydroxypropyl-?-cyclodextrin inclusion complex in thermoreversible gels for ulcerative colitis CC Oliveira, A Gambero, T Rocha, CMS Cereda, GR Tofoli Springer Science and Business Media LLC , 2020 2020
Physico-chemical characterization and biopharmaceutical evaluation of lipid-poloxamer-based organogels for curcumin skin delivery AA Vigato, SM Querobino, NC De Faria, ACBB Candido, LG Magalhães, ... Frontiers in Pharmacology 10, 1006 , 2019 2019 Citations: 32
Improved efficacy of naproxen-loaded NLC for temporomandibular joint administration VA Guilherme, LNM Ribeiro, ACS Alcântara, SR Castro, ... Scientific reports 9 (1), 11160 , 2019 2019 Citations: 81
Preclinical evaluation of ropivacaine in 2 liposomal modified systems CC Rennó, JZB Papini, CMS Cereda, E Martinez, VA Montalli, E de Paula, ... Anesthesia & Analgesia 129 (2), 387-396 , 2019 2019 Citations: 15
Efficacy of Tramadol in Thermoreversibles Gels in a Model of Postoperative Pain G Tofoli, J Papini, C Cereda, J Napimoga, C Macedo, D de Araujo The FASEB Journal 33 (S1), 820.1-820.1 , 2019 2019
Synthesis and characterization of nanostructured lipid-poloxamer organogels for enhanced skin local anesthesia AA Vigato, SM Querobino, NC de Faria, ACP de Freitas, GR Leonardi, ... European Journal of Pharmaceutical Sciences 128, 270-278 , 2019 2019 Citations: 25
Liposomal-based lidocaine formulation for the improvement of infiltrative buccal anaesthesia ACP de Almeida, LMA Pinto, GP Alves, LNM Ribeiro, MHA Santana, ... Journal of liposome research 29 (1), 66-72 , 2019 2019 Citations: 13
Association of capsaicin with local anesthetics to increase analgesia= Associação de capsaicina com anestésicos locais para aumento da analgesia VM Couto [sn] , 2019 2019
Avaliação do papel das células T e astrócitos do subnúcleo caudal trigeminal na hipernocicepção inflamatória persistente induzida pela artrite na articulação temporomandibular … R Bonfante [sn] , 2019 2019
Hybrid hydrogel composed of polymeric nanocapsules co-loading lidocaine and prilocaine for topical intraoral anesthesia BV Muniz, D Baratelli, S Di Carla, L Serpe, CB da Silva, VA Guilherme, ... Scientific Reports 8 (1), 17972 , 2018 2018 Citations: 59
Bupivacaine in alginate and chitosan nanoparticles: an in vivo evaluation of efficacy, pharmacokinetics, and local toxicity CMS Cereda, DS Mecatti, JZB Papini, DV Bueno, M Franz-Montan, ... Journal of pain research, 683-691 , 2018 2018 Citations: 21
MOST CITED SCHOLAR PUBLICATIONS
Development and pharmacological evaluation of ropivacaine-2-hydroxypropyl-β-cyclodextrin inclusion complex DR de Araujo, SS Tsuneda, CMS Cereda, FDGF Carvalho, PSC Preté, ... european journal of pharmaceutical sciences 33 (1), 60-71 , 2008 2008 Citations: 165
Micro and nanosystems for delivering local anesthetics E de Paula, CMS Cereda, LF Fraceto, DR de Araujo, M Franz-Montan, ... Expert opinion on drug delivery 9 (12), 1505-1524 , 2012 2012 Citations: 104
Recent advances and perspectives in topical oral anesthesia M Franz-Montan, LNM Ribeiro, MC Volpato, CMS Cereda, FC Groppo, ... Expert opinion on drug delivery 14 (5), 673-684 , 2017 2017 Citations: 101
Drug delivery systems for local anesthetics E de Paula, C Cereda, GR Tofoli, M Franz-Montan, LF Fraceto, ... Recent patents on drug delivery & formulation 4 (1), 23-34 , 2010 2010 Citations: 96
Liposomal formulations of prilocaine, lidocaine and mepivacaine prolong analgesic duration: [Des préparations liposomiques de prilocaïne, de lidocaïne et de mépivacaïne … CM Saia Cereda, GB Brunetto, DR de Araújo Phd, E de Paula Canadian Journal of Anesthesia/Journal canadien d'anesthésie 53 (11), 1092-1097 , 2006 2006 Citations: 92
Liposomal lidocaine gel for topical use at the oral mucosa: characterization, in vitro assays and in vivo anesthetic efficacy in humans M Franz-Montan, D Baroni, G Brunetto, VRV Sobral, CMG da Silva, ... Journal of liposome research 25 (1), 11-19 , 2015 2015 Citations: 83
Improved efficacy of naproxen-loaded NLC for temporomandibular joint administration VA Guilherme, LNM Ribeiro, ACS Alcântara, SR Castro, ... Scientific reports 9 (1), 11160 , 2019 2019 Citations: 81
Encapsulation of mepivacaine prolongs the analgesia provided by sciatic nerve blockade in mice DR de Araujo, CMS Cereda, GB Brunetto, LMA Pinto, MHA Santana, ... Canadian Journal of Anesthesia 51 (6), 566-572 , 2004 2004 Citations: 79
Strategies for delivering local anesthetics to the skin: focus on liposomes, solid lipid nanoparticles, hydrogels and patches DR de Araujo, DC da Silva, RM Barbosa, M Franz-Montan, CMS Cereda, ... Expert opinion on drug delivery 10 (11), 1551-1563 , 2013 2013 Citations: 77
Liposomal prilocaine: preparation, characterization, and in vivo evaluation CMS Cereda, DR De Araujo, GB Brunetto, E De Paula J Pharm Pharm Sci 7 (2), 235-240 , 2004 2004 Citations: 72
Local neurotoxicity and myotoxicity evaluation of cyclodextrin complexes of bupivacaine and ropivacaine CMS Cereda, GR Tofoli, LG Maturana, A Pierucci, LAS Nunes, ... Anesthesia & Analgesia 115 (5), 1234-1241 , 2012 2012 Citations: 66
Bioadhesive Films Containing Benzocaine: Correlation Between In Vitro Permeation and In Vivo Local Anesthetic Effect DR de Araujo, C Padula, CMS Cereda, GR Tófoli, RB Brito Jr, E de Paula, ... Pharmaceutical Research 27 (8), 1677-1686 , 2010 2010 Citations: 66
Pharmacological and local toxicity studies of a liposomal formulation for the novel local anaesthetic ropivacaine DR de Araujo, CMS Cereda, GB Brunetto, VU Vomero, A Pierucci, ... Journal of pharmacy and pharmacology 60 (11), 1449-1457 , 2008 2008 Citations: 62
Hybrid hydrogel composed of polymeric nanocapsules co-loading lidocaine and prilocaine for topical intraoral anesthesia BV Muniz, D Baratelli, S Di Carla, L Serpe, CB da Silva, VA Guilherme, ... Scientific Reports 8 (1), 17972 , 2018 2018 Citations: 59
Improvement of tetracaine antinociceptive effect by inclusion in cyclodextrins RA Franco de Lima, MB de Jesus, CM Saia Cereda, GR Tofoli, ... Journal of drug targeting 20 (1), 85-96 , 2012 2012 Citations: 44
Efficacy of liposome-encapsulated mepivacaine for infiltrative anesthesia in volunteers GR Tofoli, CMS Cereda, FC Groppo, MC Volpato, M Franz-Montan, ... Journal of Liposome Research 21 (1), 88-94 , 2011 2011 Citations: 42
Liposomal-benzocaine gel formulation: correlation between in vitro assays and in vivo topical anesthesia in volunteers M Franz-Montan, CMS Cereda, A Gaspari, CMG da Silva, DR de Araujo, ... Journal of liposome research 23 (1), 54-60 , 2013 2013 Citations: 38
Transdermal delivery of butamben using elastic and conventional liposomes CMS Cereda, M Franz-Montan, CMG da Silva, BR Casadei, ... Journal of liposome research 23 (3), 228-234 , 2013 2013 Citations: 33
Stability and local toxicity evaluation of a liposomal prilocaine formulation CM Saia Cereda, GR Tofoli, RB De Brito Junior, MB De Jesus, LF Fraceto, ... Journal of Liposome Research 18 (4), 329-339 , 2008 2008 Citations: 33
Physico-chemical characterization and biopharmaceutical evaluation of lipid-poloxamer-based organogels for curcumin skin delivery AA Vigato, SM Querobino, NC De Faria, ACBB Candido, LG Magalhães, ... Frontiers in Pharmacology 10, 1006 , 2019 2019 Citations: 32