The biopharmaceutical aspects of nasal mucoadhesive drug delivery

Ugwoke, Michael Ikechukwu; Verbeke, Norbert; Kinget, Renaat

doi:10.1211/0022357011775145

Cited by 295 publications

(179 citation statements)

References 103 publications

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“…According to the chemical structure of the thiolated polymer, thiolate anions are responsible for the formation of new disulfide bonds which are available at pH 6-7. Moreover, the thiolated microparticles are reported to show higher cohesive properties which are also essential for high mucoadhesion (Ugwoke et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

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Insulin delivery through nasal route using thiolated microspheres

Nema

Jain

et al. 2013

Drug Delivery

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The aim of the present study was to investigate the potential of developed thiolated microspheres for insulin delivery through nasal route. In the present study, cysteine was immobilized on carbopol using EDAC. A total of 269.93 mmol free thiol groups per gram polymer were determined. The prepared nonthiolated and thiolated microspheres were studied for particle shape, size, drug content, swellability, mucoadhesion and in vitro insulin release. The thiolated microspheres exhibited higher mucoadhesion due to formation of covalent bonds via disulfide bridges with the mucus gel layer. Drug permeation through goat nasal mucosa of nonthiolated and thiolated microspheres were found as 52.62 AE 2.4% and 78.85 AE 3.1% in 6 h, respectively. Thiolated microspheres bearing insulin showed better reduction in blood glucose level (BGL) in comparison to nonthiolated microspheres as 31.23 AE 2.12% and 75.25 AE 0.93% blood glucose of initial BGL were observed at 6 h after nasal delivery of thiolated and nonthiolated microspheres in streptozotocin-induced diabetic rabbits.

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Section: Discussionmentioning

confidence: 99%

“…Ugwoke et al (2001) reported that polymers with thiol groups provide much higher adhesive properties than polymers generally considered to be mucoadhesive. The enhancement of mucoadhesion can be explained by the formation of covalent bonds between the polymer and the mucus layer, which are stronger than noncovalent bonds.…”

Section: Introductionmentioning

confidence: 99%

Insulin delivery through nasal route using thiolated microspheres

Nema

Jain

et al. 2013

Drug Delivery

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“…Although intranasal drug delivery offers many advantages, one of the main limitations is the short residence time of the formulation in the nasal cavity, as a result of mucociliary clearance (MCC) 10 . This movement involves the beating of mucocilia at a frequency of 1,000 strokes per minute and hence movement of mucus of 5 mm/minute 11 .…”

Section: Introductionmentioning

confidence: 99%

“…To achieve this goal, the use of intelligent polymer based systems have now become more commonplace in this field and particularly the use of responsive systems which may respond to the nasal cavity temperature [13][14][15][16][17][18][19][20][21][22] or pH [23][24][25][26][27] have increased amongst researchers. Furthermore, the use of mucoadhesive polymers 4,[27][28][29][30][31][32][33] to enhance the adhesion of the formulations onto the nasal mucosa has further demonstrated the ability to prolong contact time with the mucosa and hence increase bioavailability 10,15,18,23,[34][35][36] .…”

Section: Introductionmentioning

confidence: 99%

Development and Evaluation of a Novel Intranasal Spray for the Delivery of Amantadine

Lungare

Bowen

Badhan

2016

Journal of Pharmaceutical Sciences

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The aim of this study was to develop and characterise an intranasal delivery system for amantadine (AMT). Optimal formulations (F) consisted of a thermosensitive polymer Pluronic ® 127 (P127) and either carboxy methyl cellulose (CMC) or chitosan (CS) which demonstrated gel-transition at nasal cavity temperatures (34 °C ± 1 °C). Rheologically, the loss tangent (Tan δ) confirmed a three-stage gelation phenomena at 34 °C ± 1 °C and nonNewtonian behaviour. Storage of FCMC and FCS at 4 °C for 8 weeks resulted in repeatable release profiles at 34 °C when sampled, with a Fickian mechanism earlier on but moving towards anomalous transport by week 8. Polymers (P127, CMC and CS) demonstrated no significant cellular toxicity to human nasal epithelial cells up to 4 mg/mL and up to 1 mM for AMT (IC50: 4.5 mM ± 0.05 mM). FCMC and FCS demonstrated slower release across an in-vitro human nasal airway model (43-44 % vs 79 % ± 4.58 % for AMT). Using a human nasal cast model, deposition into the olfactory regions (potential nose-to-brain) was demonstrated upon nozzle insertion (5 mm) whereas tilting of the head forward (15°) resulted in greater deposition in the bulk of the nasal cavity. KEYWORDSParkinson's disease; rheology; nasal; RPMI 2650; nose to brain; thermoresponsive; 3 INTRODUCTION Parkinson's disease (PD) is an ageing associated progressive neurological disorder and affects 1.5 % of the population over 65-years of age 1 , with age-adjusted prevalence rates thought to be around 150 per 100,000 with a suggested mean onset in the 70's 1 . Ageing is the largest single risk factor for the development of PD and the pathogenesis of PD is composed of a range of events leading towards neuronal apoptosis, primarily of degradation of dopamine neurones in the sustantia nigra. The mainstay of clinical drug therapy focuses on increases the levels of dopamine (DA) in the brain, with oral dosing of levodopa being the most commonly used to pharmacological intervention treatment to reverse the symptoms of PD. It is also common to use adjunct therapies in conjunction with levodopa, such as the weak NMDA-type receptor antagonist amantadine, which can aid in blocking dopamine reuptake.

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“…1,2) The nasal structure feature was one of the main biological factors. The nasal cavity could be anatomically segregated into five different regions: nasal vestibule, atrium, respiratory area, olfactory region and nasopharnyx.…”

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confidence: 99%

The Permeation of Nalmefene Hydrochloride across Different Regions of Ovine Nasal Mucosa

Yong-liang

Nie

et al. 2006

Chem. Pharm. Bull.

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Nasal drug delivery has been generating widespread interest in the drug delivery field because it could not only be used in local treatment but also in systemic administration. Various properties of nasal drug delivery made it an alternative route for intravenous and oral administration, such as bypassing of enzymatic or acidic degradation and exempting the first-pass hepatic metabolism; the relatively large epithelial surface, porous endothelial membranes and highly vascularized epithelium also maintained the rapid absorption of drugs.Various factors that might affect the permeability of drugs through the nasal mucosa could be broadly classified into three categories as follow: biological factors, formulation aspects and device-related factors. 1,2) The nasal structure feature was one of the main biological factors. The nasal cavity could be anatomically segregated into five different regions: nasal vestibule, atrium, respiratory area, olfactory region and nasopharnyx.2) The structure features of different regions were quite different which resulted in different blood supply, nasal secretion and mucociliary clearance among them, 3) and thus may influence the permeability of drug and presystemic degradation. Moreover, different devices and dosage forms may result in differences of the deposition place and residence time of drugs in the nasal cavity. Therefore, the research on the permeability of drug through mucosas of different regions of nasal cavity in vitro may help us to find out the main absorption region of drugs and understand the mechanism, rate and extent of drug absorption across the nasal mucosa. Furthermore, it may also be helpful for choosing dosage forms to deposit drugs on the main absorption region and prolong the residence time.However, there were few studies about the permeation of drugs through mucosas of different regions of the nasal cavity. In present study, the Valia-Chien chamber technique 4) and a hydrophilic model drug nalmefene hydrochloride [17-N-cyclopropylmethyl-3,14-b-dihydroxy-4,5-a-epoxy-6-methylene morphinan hydrochloride] 5) which was chosen for its possibility to be developed as a product for emergency medicine, 6) was used to study the permeability of the five different regions. The permeability coefficient and accumulative drug permeation was investigated. The permeation of NH through different pieces obtained from the same middle turbinate mucosa and the same septum mucosa was also investigated to evaluate the uniformity of such mucosa.The excised tissue of animals such as sheep, 7-9) pig, 10,11) rabbit, 4,12,13) and ox 14,15) had been employed by researchers to study the drug delivery through nasal mucosa. Among these animals, the morphology of the ovine mucosa is more comparable to that of humans because of the presence of ciliated and non ciliated cells, basal cells, goblet cells and serous glands. 16) In the present study, ovine nasal mucosa was employed. During the experimental process, it was easier to handle the tissue and keep the mucosa intact and unstrained. Ther...

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The biopharmaceutical aspects of nasal mucoadhesive drug delivery

Cited by 295 publications

References 103 publications

Insulin delivery through nasal route using thiolated microspheres

Insulin delivery through nasal route using thiolated microspheres

Development and Evaluation of a Novel Intranasal Spray for the Delivery of Amantadine

The Permeation of Nalmefene Hydrochloride across Different Regions of Ovine Nasal Mucosa

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