176
Views
0
CrossRef citations to date
0
Altmetric
Review

Nanotechnology-Based Mucoadhesive and Mucus-Penetrating Drug-Delivery Systems for Transbuccal Drug Delivery

, ORCID Icon, , , ORCID Icon & ORCID Icon
Pages 1495-1514 | Received 10 Jul 2023, Accepted 22 Aug 2023, Published online: 13 Oct 2023

References

  • Alqahtani MS , KaziM, AlsenaidyMA, AhmadMZ. Advances in oral drug delivery. Front. Pharmacol.12, doi: 10.3389/fphar.2021.618411 (2021) ( Online).
  • Mitchell MJ , BillingsleyMM, HaleyRM, WechslerME, PeppasNA, LangerR. Engineering precision nanoparticles for drug delivery. Nat. Rev. Drug Discov.20(2), 101–124 (2021).
  • Abramson A , KirtaneAR, ShiYet al. Oral mRNA delivery using capsule-mediated gastrointestinal tissue injections. Matter5(3), 975–987 (2022).
  • Mazzinelli E , FavuzziI, ArcovitoAet al. Oral mucosa models to evaluate drug permeability. Pharmaceutics15(5), 1559 (2023).
  • Zhang H , ZhangJ, StreisandJB. Oral mucosal drug delivery: clinical pharmacokinetics and therapeutic applications. Clin. Pharmacokinet.41(9), 661–680 (2002).
  • Lam JKW , XuY, WorsleyA, WongICK. Oral transmucosal drug delivery for pediatric use. Adv. Drug. Deliv. Rev.73, 50–62 (2014).
  • Madhav NVS , ShakyaAK, ShakyaP, SinghK. Orotransmucosal drug delivery systems: a review. J. Control. Rel.140(1), 2–11 (2009).
  • Patel VF , LiuF, BrownMB. Advances in oral transmucosal drug delivery. J. Control. Rel.153(2), 106–116 (2011).
  • Hua S . Advances in nanoparticulate drug delivery approaches for sublingual and buccal administration. Front. Pharmacol.10, doi: 10.3389/fphar.2019.01328 (2019) ( Online).
  • Shipp L , LiuF, Kerai-VarsaniL, OkwuosaTC. Buccal films: a review of therapeutic opportunities, formulations and relevant evaluation approaches. J. Control. Rel.352, 1071–1092 (2022).
  • Al-Dhubiab BE , NairAB, KumriaR, AttimaradM, HarshaS. Formulation and evaluation of nano based drug delivery system for the buccal delivery of acyclovir. Colloids Surf. B Biointerfaces136, 878–884 (2015).
  • Abd El Azim H , NafeeN, RamadanA, KhalafallahN. Liposomal buccal mucoadhesive film for improved delivery and permeation of water-soluble vitamins. Int. J. Pharm.488(1–2), 78–85 (2015).
  • Kamimori GH , KaryekarCS, OtterstetterRet al. The rate of absorption and relative bioavailability of caffeine administered in chewing gum versus capsules to normal healthy volunteers. Int. J. Pharm.234(1–2), 159–167 (2002).
  • Russell MA , MerrimanR, StapletonJ, TaylorW. Effect of nicotine chewing gum as an adjunct to general practitioner's advice against smoking. Br. Med. J. (Clin. Res. Ed.)287(6407), 1782–1785 (1983).
  • Vaidya A , MitragotriS. Ionic liquid-mediated delivery of insulin to buccal mucosa. J. Control. Rel.327, 26–34 (2020).
  • Chinna Reddy P , ChaitanyaKSC, MadhusudanRao Y. A review on bioadhesive buccal drug delivery systems: current status of formulation and evaluation methods. Daru19(6), 385 (2011).
  • Bayer IS . Recent advances in mucoadhesive interface materials, mucoadhesion characterization, and technologies. Adv. Mater. Interfaces9(18), (2022) ( Online).
  • Tran PHL , DuanW, TranTTD. Recent developments of nanoparticle-delivered dosage forms for buccal delivery. Int. J. Pharm.571, doi: 10.1016/j.ijpharm.2019.118697 (2019) ( Online).
  • Manikkath J , ParekhHS, MutalikS. Surface-engineered nanoliposomes with lipidated and non-lipidated peptide-dendrimeric scaffold for efficient transdermal delivery of a therapeutic agent: development, characterization, toxicological and preclinical performance analyses. Eur. J. Pharm. Biopharm.156, 97–113 (2020).
  • Nair AB , KumriaR, HarshaS, AttimaradM, Al-DhubiabBE, AlhaiderIA. In vitro techniques to evaluate buccal films. J. Control. Rel.166(1), 10–21 (2013).
  • Brizuela M , WintersR. Histology, oral mucosa. Updated 8 May 2023. In: StatPearls.StatPearls Publishing, FL, USA (2023). www.ncbi.nlm.nih.gov/books/NBK572115/
  • Yakubov GE , GibbinsH, ProctorGB, CarpenterGH. Oral mucosa: physiological and physicochemical aspects. In: Mucoadhesive Materials and Drug Delivery Systems.KhutoryanskiyVV ( Ed.). John Wiley and Sons, Chichester, UK, 1–38 (2014).
  • Schwartz M , NeiersF, CharlesJPet al. Oral enzymatic detoxification system: insights obtained from proteome analysis to understand its potential impact on aroma metabolization. Compr. Rev. Food Sci. Food Saf.20(6), 5516–5547 (2021).
  • Sneha R , Vedha HariBN, RamyaDevi D. Design of antiretroviral drug-polymeric nanoparticles laden buccal films for chronic HIV therapy in paediatrics. Colloid Interface Sci. Commun.27, 49–59 (2018).
  • Zhao K , XieY, LinX, XuW. The mucoadhesive nanoparticle-based delivery system in the development of mucosal vaccines. Int. J. Nanomed.17, 4579–4598 (2022).
  • Smart JD . The basics and underlying mechanisms of mucoadhesion. Adv. Drug Deliv. Rev.57(11), 1556–1568 (2005).
  • Shaikh R , RajSingh TR, GarlandM, WoolfsonA, DonnellyR. Mucoadhesive drug delivery systems. J. Pharm. Bioallied Sci.3(1), 89–100 (2011).
  • Brooks AE . The potential of silk and silk-like proteins as natural mucoadhesive biopolymers for controlled drug delivery. Front. Chem.3, 65 (2015).
  • Ponchel G , IracheJM. Specific and non-specific bioadhesive particulate systems for oral delivery to the gastrointestinal tract. Adv. Drug Deliv. Rev.34(2–3), 191–219 (1998).
  • Lai SK , WangYY, HanesJ. Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv. Drug Deliv. Rev.61(2), 158–171 (2009).
  • Roy S , PalK, AnisA, PramanikK, PrabhakarB. Polymers in mucoadhesive drug-delivery systems: a brief note. Des. Monomers Polym.12(6), 483–495 (2012).
  • Cone RA . Barrier properties of mucus. Adv. Drug Deliv. Rev.61(2), 75–85 (2009).
  • Olmsted SS , PadgettJL, YudinAI, WhaleyKJ, MoenchTR, ConeRA. Diffusion of macromolecules and virus-like particles in human cervical mucus. Biophys. J.81(4), 1930–1937 (2001).
  • Saltzman WM , RadomskyML, WhaleyKJ, ConeRA. Antibody diffusion in human cervical mucus. Biophys. J.66, 508–515 (1994).
  • Tan YL , LiuCG. Preparation and characterization of self-assembled nanoparticles based on folic acid modified carboxymethyl chitosan. J. Mater. Sci. Mater. Med.22(5), 1213–1220 (2011).
  • Manikkath J , SumathyT, ManikkathA, MutalikS. Delving deeper into dermal and transdermal drug delivery: factors and mechanisms associated with nanocarrier-mediated strategies. Curr. Pharm. Des.24(27), 3210–3222 (2018).
  • Hua S , de MatosMBC, MetselaarJM, StormG. Current trends and challenges in the clinical translation of nanoparticulate nanomedicines: pathways for translational development and commercialization. Front. Pharmacol.9, 790 (2018).
  • Gómez-Guillén MC , MonteroMP. Enhancement of oral bioavailability of natural compounds and probiotics by mucoadhesive tailored biopolymer-based nanoparticles: a review. Food Hydrocoll.118, doi: 10.1016/j.foodhyd.2021.106772 (2021) ( Online).
  • Mansuri S , KesharwaniP, JainK, TekadeRK, JainNK. Mucoadhesion: a promising approach in drug delivery system. React. Funct. Polym.100, 151–172 (2016).
  • Crater JS , CarrierRL. Barrier properties of gastrointestinal mucus to nanoparticle transport. Macromol. Biosci.10(12), 1473–1483 (2010).
  • Roblegg E , FröhlichE, MeindlC, TeublB, ZaverskyM, ZimmerA. Evaluation of a physiological in vitro system to study the transport of nanoparticles through the buccal mucosa. Nanotoxicology6(4), 399–413 (2012).
  • Bashyal S , SeoJE, KeumT, NohG, LamichhaneS, LeeS. Development, characterization, and ex vivo assessment of elastic liposomes for enhancing the buccal delivery of insulin. Pharmaceutics13(4) (2021).
  • Smistad G , JacobsenJ, SandeSA. Multivariate toxicity screening of liposomal formulations on a human buccal cell line. Int. J. Pharm.330(1–2), 14–22 (2007).
  • Okafor NI , NgoepeM, NoundouXS, MaçedoKrause RW. Nano-enabled liposomal mucoadhesive films for enhanced efavirenz buccal drug delivery. J. Drug Deliv. Sci. Technol.54, doi: 10.1016/j.jddst.2019.101312 (2019) ( Online).
  • Zewail MB , FAsaad G, SwellamSMet al. Design, characterization and in vivo performance of solid lipid nanoparticles (SLNs)-loaded mucoadhesive buccal tablets for efficient delivery of Lornoxicam in experimental inflammation. Int. J. Pharm.624, doi: 10.1016/j.ijpharm.2022.122006 (2022) ( Online).
  • Tzanova MM , HagesaetherE, ThoI. Solid lipid nanoparticle-loaded mucoadhesive buccal films – critical quality attributes and in vitro safety and efficacy. Int. J. Pharm.592, doi: 10.1016/j.ijpharm.2020.120100 (2021) ( Online).
  • Kraisit P , HirunN, MahadlekJ, LimmatvapiratS. Fluconazole-loaded solid lipid nanoparticles (SLNs) as a potential carrier for buccal drug delivery of oral candidiasis treatment using the Box–Behnken design. J. Drug Deliv. Sci. Technol.63, doi: 10.1016/j.jddst.2021.102437 (2021) ( Online).
  • Ho HN , LeHH, LeTGet al. Formulation and characterization of hydroxyethyl cellulose-based gel containing metronidazole-loaded solid lipid nanoparticles for buccal mucosal drug delivery. Int. J. Biol. Macromol.194, 1010–1018 (2022).
  • Jeitler R , GladerC, TetyczkaCet al. Investigation of cellular interactions of lipid-structured nanoparticles with oral mucosal epithelial cells. Front. Mol. Biosci.9, doi: 10.3389/fmolb.2022.917921 (2022) ( Online).
  • Rahbarian M , MortazavianE, DorkooshFA, RafieeTehrani M. Preparation, evaluation and optimization of nanoparticles composed of thiolated triethyl chitosan: a potential approach for buccal delivery of insulin. J. Drug Deliv. Sci. Technol.44, 254–263 (2018).
  • Amin MK , BoatengJS. Enhancing stability and mucoadhesive properties of chitosan nanoparticles by surface modification with sodium alginate and polyethylene glycol for potential oral mucosa vaccine delivery. Mar. Drugs20(3), 156 (2022).
  • Al-Nemrawi NK , AlsharifSSM, AlzoubiKH, AlkhatibRQ. Preparation and characterization of insulin chitosan-nanoparticles loaded in buccal films. Pharm. Dev. Technol.24(8), 967–974 (2019).
  • Suh JW , LeeJS, KoS, LeeHG. Preparation and characterization of mucoadhesive buccal nanoparticles using chitosan and dextran sulfate. J. Agric. Food Chem.64(26), 5384–5388 (2016).
  • Goldberg M , ManziA, ConwayPet al. A nanoengineered topical transmucosal cisplatin delivery system induces anti-tumor response in animal models and patients with oral cancer. Nat. Commun.13(1), 1–14 (2022).
  • Giovino C , AyensuI, TettehJ, BoatengJS. Development and characterisation of chitosan films impregnated with insulin loaded PEG-b-PLA nanoparticles (NPs): a potential approach for buccal delivery of macromolecules. Int. J. Pharm.428(1–2), 143–151 (2012).
  • Giovino C , AyensuI, TettehJ, BoatengJS. An integrated buccal delivery system combining chitosan films impregnated with peptide loaded PEG-b-PLA nanoparticles. Colloids Surf. B Biointerfaces112, 9–15 (2013).
  • Ho HN , NguyenVAT, HoNAT, LeHH. Development of a hydrogel containing metronidazole-loaded Eudragit RS 100 nanoparticles for buccal drug delivery. Trop. J. Pharm. Res.22(6), 1147–1154 (2023).
  • Castro PM , BaptistaP, MadureiraAR, SarmentoB, PintadoME. Combination of PLGA nanoparticles with mucoadhesive guar-gum films for buccal delivery of antihypertensive peptide. Int. J. Pharm.547(1–2), 593–601 (2018).
  • Castro PM , BaptistaP, ZuccheriG, MadureiraAR, SarmentoB, PintadoME. Film-nanoparticle composite for enhanced oral delivery of alpha-casozepine. Colloids Surf. B Biointerfaces181, 149–157 (2019).
  • Castro PM , SousaF, MagalhãesRet al. Incorporation of beads into oral films for buccal and oral delivery of bioactive molecules. Carbohydr. Polym.194, 411–421 (2018).
  • Liang H , HuangQ, ZhouBet al. Self-assembled zein–sodium carboxymethyl cellulose nanoparticles as an effective drug carrier and transporter. J. Mater. Chem. B3(16), 3242–3253 (2015).
  • Wang K , LiuT, LinRet al. Preparation and in vitro release of buccal tablets of naringenin-loaded MPEG-PCL nanoparticles. RSC Adv.4(64), 33672–33679 (2014).
  • Rodrigues DA , MiguelSP, LoureiroJ, RibeiroM, RoqueF, CoutinhoP. Oromucosal alginate films with zein nanoparticles as a novel delivery system for digoxin. Pharmaceutics13(12), 2030 (2021).
  • Mašek J , LubasováD, LukáčRet al. Multi-layered nanofibrous mucoadhesive films for buccal and sublingual administration of drug-delivery and vaccination nanoparticles – important step towards effective mucosal vaccines. J. Control. Rel.249, 183–195 (2017).
  • Hashem HM , MotaweaA, KamelAH, BaryEMA, HassanSSM. Fabrication and characterization of electrospun nanofibers using biocompatible polymers for the sustained release of venlafaxine. Sci. Rep.12(1), 1–16 (2022).
  • Zhou L , LiA, WangH, SunW, ZuoS, LiC. Preparation and characterization of luteolin-loaded MPEG-PCL-g-PEI micelles for oral Candida albicans infection. J. Drug Deliv. Sci. Technol.63, doi: 10.1016/j.jddst.2021.102454 (2021) ( Online).
  • de Souza Ferreira SB , BragaG, deOliveira ÉLet al. Colloidal systems composed of poloxamer 407, different acrylic acid derivatives and curcuminoids: optimization of preparation method, type of bioadhesive polymer and storage conditions. J. Drug Deliv. Sci. Technol.57, doi: 10.1016/j.jddst.2020.101686 (2020) ( Online).
  • Ouellette M , MasseF, Lefebvre-DemersMet al. Insights into gold nanoparticles as a mucoadhesive system. Sci. Rep.8(1), 1–15 (2018).
  • Essawy MM , El-SheikhSM, RaslanHSet al. Function of gold nanoparticles in oral cancer beyond drug delivery: implications in cell apoptosis. Oral Dis.27(2), 251–265 (2021).
  • Wang S , JiangL, MengSet al. Hollow mesoporous silica nanoparticles-loaded ion-crosslinked bilayer films with excellent mechanical properties and high bioavailability for buccal delivery. Int. J. Pharm.624, doi: 10.1016/j.ijpharm.2022.122056 (2022) ( Online).
  • Yuan Q , FuY, KaoWJ, JanigroD, YangH. Transbuccal delivery of CNS therapeutic nanoparticles: synthesis, characterization, and in vitro permeation studies. ACS Chem. Neurosci.2(11), 676–683 (2011).
  • Lai SK , O'HanlonDE, HarroldSet al. Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus. Proc. Natl Acad. Sci. USA104(5), 1482–1487 (2007).
  • Schuster BS , EnsignLM, AllanDB, SukJS, HanesJ. Particle tracking in drug and gene delivery research: state-of-the-art applications and methods. Adv. Drug. Deliv. Rev.91, 70–91 (2015).
  • McCarron PA , DonnellyRF, CanningPE, McGovernJG, JonesDS. Bioadhesive, non-drug-loaded nanoparticles as modulators of candidal adherence to buccal epithelial cells: a potentially novel prophylaxis for candidosis. Biomaterials25(12), 2399–2407 (2004).
  • Rao S , SongY, PeddieF, EvansAM. Particle size reduction to the nanometer range: a promising approach to improve buccal absorption of poorly water-soluble drugs. Int. J. Nanomed.6, 1245–1251 (2011).
  • Ourique AF , PohlmannAR, GuterresSS, BeckRCR. Tretinoin-loaded nanocapsules: preparation, physicochemical characterization, and photostability study. Int. J. Pharm.352(1–2), 1–4 (2008).
  • Morales JO , HuangS, WilliamsRO, McConvilleJT. Films loaded with insulin-coated nanoparticles (ICNP) as potential platforms for peptide buccal delivery. Colloids Surf. B Biointerfaces122, 38–45 (2014).
  • Morales JO , McConvilleJT. Manufacture and characterization of mucoadhesive buccal films. Eur. J. Pharm. Biopharm.77(2), 187–199 (2011).
  • Salehi S , BoddohiS. New formulation and approach for mucoadhesive buccal film of rizatriptan benzoate. Prog. Biomater.6(4), 175–187 (2017).
  • Boateng J , ManiJ, KianfarF. Improving drug loading of mucosal solvent cast films using a combination of hydrophilic polymers with amoxicillin and paracetamol as model drugs. Biomed. Res. Int.2013 (2013).
  • Silva BMA , BorgesAF, SilvaC, CoelhoJFJ, SimõesS. Mucoadhesive oral films: the potential for unmet needs. Int. J. Pharm.494(1), 537–551 (2015).
  • Shah RB , PatelM, MaahsDM, ShahVN. Insulin delivery methods: past, present and future. Int. J. Pharm. Investig.6(1), 1 (2016).
  • Bashir S , FitaihiR, AbdelhakimHE. Advances in formulation and manufacturing strategies for the delivery of therapeutic proteins and peptides in orally disintegrating dosage forms. Eur. J. Pharm. Sci.182 (2023).
  • Nagai T , MachidaY. Buccal delivery systems using hydrogels. Adv. Drug Deliv. Rev.11(1–2), 179–191 (1993).
  • Russo E , SelminF, BaldassariSet al. A focus on mucoadhesive polymers and their application in buccal dosage forms. J. Drug Deliv. Sci. Technol.32, 113–125 (2016).
  • Singh B , PalL. Radiation crosslinking polymerization of sterculia polysaccharide–PVA–PVP for making hydrogel wound dressings. Int. J. Biol. Macromol.48(3), 501–510 (2011).
  • Mahmoud GA , AliAEH, RaafatAI, BadawyNA, ElshahawyMF. Development of (acrylic acid/polyethylene glycol)-zinc oxide mucoadhesive nanocomposites for buccal administration of propranolol HCl. Radiat. Phys. Chem. Oxf.147, 18–26 (2018).
  • El-Hag Ali A , AlarifiAS. Swelling and drug release profile of poly(2-ethyl-2-oxazoline)-based hydrogels prepared by gamma radiation-induced copolymerization. J. Appl. Polym. Sci.120(5), 3071–3077 (2011).
  • Hearnden V , SankarV, HullKet al. New developments and opportunities in oral mucosal drug delivery for local and systemic disease. Adv. Drug Deliv. Rev.64(1), 16–28 (2012).
  • Fini A , BergamanteV, CeschelGC. Mucoadhesive gels designed for the controlled release of chlorhexidine in the oral cavity. Pharmaceutics3(4), 665–679 (2011).
  • Cook SL , BullSP, MethvenL, ParkerJK, KhutoryanskiyVV. Mucoadhesion: a food perspective. Food Hydrocoll.72, 281–296 (2017).
  • Ashri LY , AbouEl Ela AESF, IbrahimMA, AlshoraDH, NaguibMJ. Optimization and evaluation of chitosan buccal films containing tenoxicam for treating chronic periodontitis: in vitro and in vivo studies. J. Drug Deliv. Sci. Technol.57, doi: 10.1016/j.jddst.2020.101720 (2020) ( Online).
  • Hirpara MR , ManikkathJ, SivakumarKet al. Long circulating PEGylated-chitosan nanoparticles of rosuvastatin calcium: development and in vitro and in vivo evaluations. Int. J. Biol. Macromol.107(Pt B), 2190–2200 (2018).
  • Calvo P , Vila-JatoJL, AlonsoMJ. Evaluation of cationic polymer-coated nanocapsules as ocular drug carriers. Int. J. Pharm.153(1), 41–50 (1997).
  • Mahdizadeh Barzoki Z , Emam-DjomehZ, MortazavianEet al. Determination of diffusion coefficient for released nanoparticles from developed gelatin/chitosan bilayered buccal films. Int. J. Biol. Macromol.112, 1005–1013 (2018).
  • Mortazavian E , AminiM, DorkooshFAet al. Preparation, design for optimization and in vitro evaluation of insulin nanoparticles integrating thiolated chitosan derivatives. J. Drug Deliv. Sci. Technol.24(1), 40–49 (2014).
  • Abdelhaleem Ali AM , AboEl-Enin HA. In-vitro/in-vivo evaluation of paclitaxel freeze-dried micellar nanoparticles intended for buccal delivery. J. Drug Deliv. Sci. Technol.62, doi: 10.1016/j.jddst.2021.102424 (2021) ( Online).
  • Lv Q , ShenC, LiXet al. Mucoadhesive buccal films containing phospholipid-bile salts-mixed micelles as an effective carrier for cucurbitacin B delivery. Drug Deliv.22(3), 351–358 (2015).
  • Gavin A , PhamJT, WangD, BrownlowB, ElbayoumiTA. Layered nanoemulsions as mucoadhesive buccal systems for controlled delivery of oral cancer therapeutics. Int. J. Nanomed.10(1), 1569–1584 (2015).
  • Itin C , KomargodskiR, DombAJ, HoffmanA. Controlled delivery of apomorphine through buccal mucosa, towards a noninvasive administration method in Parkinson's disease: a preclinical mechanistic study. J. Pharm. Sci.109(9), 2729–2734 (2020).
  • Dong Z , LinY, XuSet al. NIR-triggered tea polyphenol-modified gold nanoparticles-loaded hydrogel treats periodontitis by inhibiting bacteria and inducing bone regeneration. Mater. Des.225, doi: 10.1016/j.matdes.2022.111487 (2023) ( Online).
  • Rana P , MurthyRSR. Formulation and evaluation of mucoadhesive buccal films impregnated with carvedilol nanosuspension: a potential approach for delivery of drugs having high first-pass metabolism. Drug Deliv.20(5), 224–235 (2013).
  • Dhanuthai K , RojanawatsirivejS, ThosapornWet al. Oral cancer: a multicenter study. Med. Oral Patol. Oral Cir. Bucal.23(1), e23–e29 (2018).
  • Johnson DE , BurtnessB, LeemansCR, LuiVWY, BaumanJE, GrandisJR. Head and neck squamous cell carcinoma. Nat. Rev. Dis. Primers6(1), 1–22 (2020).
  • Anand U , DeyA, ChandelAKSet al. Cancer chemotherapy and beyond: current status, drug candidates, associated risks and progress in targeted therapeutics. Genes Dis.10(4), 1367–1401 (2022).
  • Moorthi C , ManavalanR, KathiresanK. Nanotherapeutics to overcome conventional cancer chemotherapy limitations. J. Pharm. Pharm. Sci.14(1), 67–77 (2011).
  • Manikkath J , JishnuPV, WichPR, ManikkathA, RadhakrishnanR. Nanoparticulate strategies for the delivery of miRNA mimics and inhibitors in anticancer therapy and its potential utility in oral submucous fibrosis. Nanomedicine (Lond.)17(3), 181–195 (2022).
  • Elsayed A , Al-RemawiM, JaberN, Abu-SalahKM. Advances in buccal and oral delivery of insulin. Int. J. Pharm.633 (2023).
  • Banerjee A , IbsenK, BrownT, ChenR, AgatemorC, MitragotriS. Ionic liquids for oral insulin delivery. Proc. Natl Acad. Sci. USA115(28), 7296–7301 (2018).
  • Hajishengallis G , ChavakisT. Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities. Nat. Rev. Immunol.21(7), 426–440 (2021).
  • Kitamoto S , Nagao-KitamotoH, JiaoYet al. The intermucosal connection between the mouth and gut in commensal pathobiont-driven colitis. Cell182(2), 447–462.e14 (2020).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.