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1.
Clin Neuropharmacol ; 47(5): 150-156, 2024.
Article in English | MEDLINE | ID: mdl-39258554

ABSTRACT

OBJECTIVE: This study aimed to explore the efficacy of the clonidine adhesive patch for participants with Tourette syndrome (TS). METHODS: This randomized, double-blind, placebo-controlled, multicenter phase IV clinical trial included participants with TS at 20 centers between May 2012 and March 2015. Treatment efficacy at week 8 was the primary outcome. The Clinical Global Impression-Severity scale and Improvement scale were the secondary endpoints. RESULTS: This trial included 488 participants, with 121 participants in the 2.0-mg/wk group, 119 participants in the 1.5-mg/wk group, 126 participants in the 1.0-mg/wk group, and 122 participants in the placebo group. For Yale Global Tic Severity Scale score reduction rate, compared with the placebo group (39.60 ± 25.56), those of the 2.0-mg/wk group (63.21 ± 32.60) and the 1.5-mg/wk group (68.16 ± 25.88) were statistically significantly different (all P < 0.001). For total Yale Global Tic Severity Scale score, compared with the placebo group (17.0 ± 8.03), the score for the 2.0-mg/wk group was 9.9 ± 8.36 ( P < 0.001); 1.5-mg/wk group, 9.6 ± 8.03 ( P < 0.001); and 1.0-mg/wk group, 10.5 ± 9.28 ( P < 0.001). The Clinical Global Impression-Severity scale and Improvement scale scores were statistically significantly different in the 3 clonidine (or experimental) groups compared with the placebo group (all P < 0.001). CONCLUSIONS: Larger doses of the clonidine adhesive patch such as 1.5 and 2.0 mg/wk are effective in improving the symptoms and overall function of participants with TS.


Subject(s)
Clonidine , Tourette Syndrome , Humans , Tourette Syndrome/drug therapy , Clonidine/administration & dosage , Clonidine/therapeutic use , Double-Blind Method , Male , Female , Adolescent , Treatment Outcome , Adult , Young Adult , Child , Transdermal Patch , Adhesives/administration & dosage , Severity of Illness Index , Adrenergic alpha-2 Receptor Agonists/administration & dosage , Adrenergic alpha-2 Receptor Agonists/therapeutic use , Dose-Response Relationship, Drug
2.
Int J Pharm ; 665: 124707, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-39284425

ABSTRACT

Over 90 % of chiral drugs applied in transdermal drug delivery system (TDDS) are racemates, significantly increasing risks of side effects. Herein, we designed a chiral molecularly imprinted patch (CMIP) that achieved enantioselectively controlled release of S-enantiomers (eutomers) and inhibited the release of R-enantiomers (distomers) for transdermal drug delivery. It is composed of chiral pressure sensitive adhesive (PSA) and molecularly imprinted polymers (MIP), showing better transdermal delivery of S-enantiomers than that of R-enantiomers in vitro (1.86-fold) and in vivo (3.74-fold), significantly decreasing the intake of distomers. Additionally, synthesized fluorescent probe enantiomers visualized enantioselective process of CMIP. Furthermore, investigations of molecular mechanism indicated that dependence on spatial conformation was dominant. On one hand, imprinted cavity of MIP with D-isomer and stronger chiral interaction with R-enantiomers led to more specific adsorption. On the other hand, L-isomer of PSA controlled the release of S-enantiomers by multiple interaction including chiral H-bond, π-π interaction and Van der Waals force. Tthus, the innovatively designed transdermal patch with enantioselective ability released eutomers of racemate and simultaneously inhibited release of distomers, significantly improving therapeutical efficiency and avoiding overdose.


Subject(s)
Administration, Cutaneous , Delayed-Action Preparations , Drug Liberation , Transdermal Patch , Stereoisomerism , Animals , Skin Absorption/drug effects , Male , Molecular Imprinting/methods , Drug Delivery Systems , Molecularly Imprinted Polymers/chemistry , Polymers/chemistry , Rats, Sprague-Dawley , Adhesives/chemistry , Adhesives/administration & dosage
3.
Nanoscale ; 16(35): 16485-16499, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39135488

ABSTRACT

Central nervous system tuberculosis (CNS-TB) is a severe form of extra-pulmonary tuberculosis with high mortality and morbidity rates. The standard treatment regimen for CNS-TB parallels that of pulmonary TB, despite the challenge posed by the blood-brain barrier (BBB), which limits the efficacy of first-line anti-TB drugs (ATDs). Nose-to-brain (N2B) drug delivery offers a promising solution for achieving high ATD concentrations directly at infection sites in the brain while bypassing the BBB. This study aimed to develop chitosan nanoparticles encapsulating ATDs, specifically isoniazid (INH) and rifampicin (RIF). These nanoparticles were further processed into micro-sized chitosan nano-aggregates (NA) via spray drying. Both INH-NA and RIF-NA showed strong mucoadhesion and significantly higher permeation rates across RPMI 2650 cells compared to free ATDs. Intranasal administration of these NAs to TB-infected mice for four weeks resulted in a significant reduction of mycobacterial load by approximately ∼2.86 Log 10 CFU compared to the untreated group. This preclinical data highlights the efficacy of intranasal chitosan nano-aggregates in treating CNS-TB, demonstrating high therapeutic potential, and addressing brain inflammation challenges. To our knowledge, this study is the first to show nasal delivery of ATD nano-formulations for CNS-TB management.


Subject(s)
Antitubercular Agents , Chitosan , Isoniazid , Nanoparticles , Rifampin , Tuberculosis, Central Nervous System , Animals , Mice , Tuberculosis, Central Nervous System/drug therapy , Blood-Brain Barrier , Chitosan/administration & dosage , Chitosan/chemistry , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Administration, Intranasal , Epithelial Cells/drug effects , Antitubercular Agents/administration & dosage , Antitubercular Agents/chemistry , Mice, Inbred BALB C , Adhesives/administration & dosage , Adhesives/chemistry , Mucins/chemistry , Brain/drug effects , Brain/pathology , Humans , Cell Line , Isoniazid/administration & dosage , Rifampin/administration & dosage , Drug Delivery Systems
4.
J Control Release ; 371: 193-203, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38782066

ABSTRACT

Microneedle patches have been developed as favorable platforms for delivery systems, such as the locoregional application of therapeutic drugs, and implantation systems, such as electronic devices on visceral tissue surfaces. However, the challenge lies in finding materials that can achieve both biocompatibility and stable fixation on the target tissue. To address this issue, utilizing a biocompatible adhesive biomaterial allows the flat part of the patch to adhere as well, enabling double-sided adhesion for greater versatility. In this work, we propose an adhesive microneedle patch based on mussel adhesive protein (MAP) with enhanced mechanical strength via ultraviolet-induced polyacrylate crosslinking and Coomassie brilliant blue molecules. The strong wet tissue adhesive and biocompatible nature of engineered acrylated-MAP resulted in the development of a versatile wet adhesive microneedle patch system for in vivo usage. In a mouse tumor model, this microneedle patch effectively delivered anticancer drugs while simultaneously sealing the skin wound. Additionally, in an application of rat subcutaneous implantation, an electronic circuit was stably anchored using a double-sided wet adhesive microneedle patch, and its signal location underneath the skin did not change over time. Thus, the proposed acrylated-MAP-based wet adhesive microneedle patch system holds great promise for biomedical applications, paving the way for advancements in drug delivery therapeutics, tissue engineering, and implantable electronic medical devices.


Subject(s)
Drug Delivery Systems , Needles , Proteins , Animals , Proteins/administration & dosage , Microinjections/methods , Rats, Sprague-Dawley , Transdermal Patch , Tissue Adhesives/administration & dosage , Mice , Humans , Antineoplastic Agents/administration & dosage , Male , Cell Line, Tumor , Rats , Female , Mice, Inbred BALB C , Skin/metabolism , Adhesives/administration & dosage , Acrylates/chemistry , Acrylates/administration & dosage
5.
J Control Release ; 370: 643-652, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38744344

ABSTRACT

Neonatal hypoglycemia is a common disease in newborns, which can precipitate energy shortage and follow by irreversible brain and neurological injury. Herein, we present a novel approach for treating neonatal hypoglycemia involving an adhesive polyvinylpyrrolidone/gallic acid (PVP/GA) film loading glucose. The PVP/GA film with loose cross-linking can be obtained by mixing their ethanol solution and drying complex. When depositing this soft film onto wet tissue, it can absorb interfacial water to form a hydrogel with a rough surface, which facilitates tight contact between the hydrogel and tissue. Meanwhile, the functional groups in the hydrogels and tissues establish both covalent and non-covalent bonds, leading to robust bioadhesion. Moreover, the adhered PVP/GA hydrogel can be detached without damaging tissue as needed. Furthermore, the PVP/GA films exhibit excellent antibacterial properties and biocompatibility. Notably, these films effectively load glucose and deliver it to the sublingual tissue of newborn rabbits, showcasing a compelling therapeutic effect against neonatal hypoglycemia. The strengths of the PVP/GA film encompass excellent wet adhesion in the wet and highly dynamic environment of the oral cavity, on-demand detachment, antibacterial efficacy, biocompatibility, and straightforward preparation. Consequently, this innovative film holds promise for diverse biomedical applications, including but not limited to wearable devices, sealants, and drug delivery systems.


Subject(s)
Animals, Newborn , Glucose , Hypoglycemia , Povidone , Animals , Rabbits , Glucose/administration & dosage , Glucose/chemistry , Povidone/chemistry , Infant, Newborn , Humans , Hydrogels/administration & dosage , Hydrogels/chemistry , Adhesives/administration & dosage , Adhesives/chemistry , Anti-Bacterial Agents/administration & dosage , Drug Delivery Systems
6.
Comput Math Methods Med ; 2021: 8212518, 2021.
Article in English | MEDLINE | ID: mdl-34887942

ABSTRACT

Bleeding and infection can cause significant increases in mortalities. Hydrogel sealants have attracted extensive attention for their ability to control bleeding. In this study, the adjuvant treatment with antibacterial adhesive hydrogel dressings was applied to patients with deep second-degree burns/scalds. The traditional medical dressing was regarded as control adjuvant treatment. The results indicated that the total positive rate of bacteria in wound secretions and the pain during dressing change in patients who used antibacterial adhesive hydrogel dressings were significantly reduced. The number of fibroblasts and new capillaries in the granulation tissue of the wound increased, and the patient's wound healing is accelerated. The overall clinical effectiveness has been significantly improved. It is proven that the antibacterial adhesive hydrogel dressing has a significant effect on wound healing.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Bandages , Wound Healing/drug effects , Adhesives/administration & dosage , Adolescent , Adult , Aged , Burns/microbiology , Burns/pathology , Burns/therapy , Capillaries/pathology , Computational Biology , Female , Fibroblasts/pathology , Granulation Tissue/blood supply , Granulation Tissue/pathology , Humans , Hydrogels/administration & dosage , Male , Middle Aged , Nanoparticles/administration & dosage , Treatment Outcome , Wound Healing/physiology , Young Adult
7.
Br J Radiol ; 94(1125): 20201208, 2021 Sep 01.
Article in English | MEDLINE | ID: mdl-34319810

ABSTRACT

OBJECTIVE: To compare the efficacy of medical adhesive and hookwire as CT-guided non-palpable pulmonary nodule (NPN) localization methods before video-assisted thoracoscopic surgery (VATS) resection, and determine the risk factors for common complications during localization. METHODS: This was a single-center non-randomized retrospective study. 102 consecutive patients with 109 NPNs were divided into Group A (medical adhesive, 66 patients, 72 nodules) and Group B (hookwire, 36 patients, 37 nodules) before VATS. Patient- and nodule-based characteristics were compared. Logistic regression was performed to identify the risk factors for complications. RESULTS: Localization was successfully performed in all the NPNs. For Group A, the rate of pneumothorax immediately after localization was lower (p = 0.049) and the localization-to-surgery interval was longer (p = 0.011) than Group B. There was no significant difference in rates of hemorrhage after needle withdrawal between the two groups (p = 0.198). Hookwire ( vs medical adhesive) (ß = 1.12, p = 0.018), total insertion depth (ß = -0.41, p = 0.013), pleura-needle angle (ß = -0.04, p = 0.025) and grade of hemorrhage after needle withdrawal (ß = -0.96, p = 0.030) were independently associated with pneumothorax, while age (ß = -0.94, p = 0.018), tumor size (ß = 0.29, p = 0.007) and its distance from the pleural surface (ß = 0.14, p = 0.004) were associated with higher grade hemorrhage after needle withdrawal. CONCLUSION: Compared with hookwire, localization with medical adhesive excelled in lower risk of pneumothorax, a more flexible localization-to-surgery interval, and had similar rates of hemorrhage after needle withdrawal. Hookwire is an independent risk factor of pneumothorax immediately after localization. ADVANCES IN KNOWLEDGE: This study added new clinical evidence to the efficacy of medical adhesive in pre-operative CT-guided NPN localization.


Subject(s)
Adhesives/administration & dosage , Lung Neoplasms/surgery , Multiple Pulmonary Nodules/surgery , Preoperative Care/methods , Radiography, Interventional/methods , Solitary Pulmonary Nodule/surgery , Tomography, X-Ray Computed/methods , Female , Humans , Lung/diagnostic imaging , Lung/surgery , Lung Neoplasms/diagnostic imaging , Male , Middle Aged , Multiple Pulmonary Nodules/diagnostic imaging , Retrospective Studies , Risk Factors , Solitary Pulmonary Nodule/diagnostic imaging , Thoracic Surgery, Video-Assisted/methods
8.
Proc Natl Acad Sci U S A ; 118(29)2021 07 20.
Article in English | MEDLINE | ID: mdl-34292870

ABSTRACT

The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2), presents an urgent health crisis. More recently, an increasing number of mutated strains of SARS-CoV-2 have been identified globally. Such mutations, especially those on the spike glycoprotein to render its higher binding affinity to human angiotensin-converting enzyme II (hACE2) receptors, not only resulted in higher transmission of SARS-CoV-2 but also raised serious concerns regarding the efficacies of vaccines against mutated viruses. Since ACE2 is the virus-binding protein on human cells regardless of viral mutations, we design hACE2-containing nanocatchers (NCs) as the competitor with host cells for virus binding to protect cells from SARS-CoV-2 infection. The hACE2-containing NCs, derived from the cellular membrane of genetically engineered cells stably expressing hACE2, exhibited excellent neutralization ability against pseudoviruses of both wild-type SARS-CoV-2 and the D614G variant. To prevent SARS-CoV-2 infections in the lung, the most vulnerable organ for COVID-19, we develop an inhalable formulation by mixing hACE2-containing NCs with mucoadhesive excipient hyaluronic acid, the latter of which could significantly prolong the retention of NCs in the lung after inhalation. Excitingly, inhalation of our formulation could lead to potent pseudovirus inhibition ability in hACE2-expressing mouse model, without imposing any appreciable side effects. Importantly, our inhalable hACE2-containing NCs in the lyophilized formulation would allow long-term storage, facilitating their future clinical use. Thus, this work may provide an alternative tactic to inhibit SARS-CoV-2 infections even with different mutations, exhibiting great potential for treatment of the ongoing COVID-19 epidemic.


Subject(s)
COVID-19/prevention & control , Nanostructures/administration & dosage , SARS-CoV-2/drug effects , Adhesives/administration & dosage , Adhesives/chemistry , Adhesives/pharmacokinetics , Administration, Inhalation , Angiotensin-Converting Enzyme 2/metabolism , Animals , Cryoprotective Agents/chemistry , Drug Storage , Epithelial Cells/metabolism , Excipients/administration & dosage , Excipients/chemistry , Excipients/pharmacokinetics , HEK293 Cells , Humans , Hyaluronic Acid/administration & dosage , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacokinetics , Lung/drug effects , Lung/metabolism , Lung/virology , Mice , Mice, Transgenic , Nanostructures/chemistry , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Virus Attachment/drug effects
9.
AAPS PharmSciTech ; 22(4): 150, 2021 May 10.
Article in English | MEDLINE | ID: mdl-33973096

ABSTRACT

Suspension-based matrix transdermal delivery systems (TDSs) are specialized systems that maintain a continuous driving force for drug delivery over prolonged wear. The pressure-sensitive adhesive (PSA) is the most critical constituent of such systems. Our study aimed to determine the effect of different mixing methods on the performance of silicone PSA-based suspension TDSs. Lidocaine suspension TDSs were prepared using conventional slow rotary mixing, high-speed homogenization, bead-mill homogenization, vortex shaking, and by an unguator. Resultant TDSs were tested for tack, shear, and peel properties and correlated to coat weight, content uniformity, microstructure, and in vitro permeation across dermatomed human skin. Every mixing method tested caused a significant reduction in peel. However, bead-mill homogenization resulted in significant loss of all adhesive properties tested, while unguator-mixed TDSs retained most properties. Good linear correlation (R2 = 1.000) between the shear properties of the TDSs with the average cumulative amount of lidocaine permeated after 24 h was observed, with no significant difference between percutaneous delivery from slow rotary-mixed systems (1334 ± 59.21 µg/cm2) and unguator-mixed systems (1147 ± 108.3 µg/cm2). However, significantly lower delivery from bead-mill homogenized systems (821.1 ± 28.00 µg/cm2) was noted. While many factors affect TDS performance, careful consideration must also be given to the processing parameters during development as they have been shown to affect the resultant system's therapeutic efficacy. Extensive mixing with bead-mill homogenization demonstrated crystallization of drug, loss in adhesive properties, coat weight, and film thickness, with reduced transdermal delivery of lidocaine from the prepared system.


Subject(s)
Adhesives/administration & dosage , Adhesives/chemical synthesis , Drug Delivery Systems/methods , Skin Absorption/drug effects , Transdermal Patch , Adhesives/pharmacokinetics , Administration, Cutaneous , Anesthetics, Local/administration & dosage , Anesthetics, Local/chemical synthesis , Anesthetics, Local/pharmacokinetics , Humans , Lidocaine/administration & dosage , Lidocaine/chemical synthesis , Lidocaine/pharmacokinetics , Mineral Oil/administration & dosage , Mineral Oil/chemical synthesis , Mineral Oil/pharmacokinetics , Organ Culture Techniques , Silicones/metabolism , Silicones/pharmacology , Skin Absorption/physiology , Suspensions
10.
CNS Neurosci Ther ; 27(7): 857-861, 2021 07.
Article in English | MEDLINE | ID: mdl-34050606

ABSTRACT

Microvascular Decompression for Hemifacial Spasm Involving the Vertebral Artery (VA): A Modified Effective Technique Using a Gelatin Sponge with a FuAiLe Medical Adhesive. (a)The VA pushes the anterior inferior cerebellar artery (AICA) which compressed the root exit zone (REZ) of the facial nerve. (b) The VA was adhered to the petrous dura, and the AICA was decompressed from the REZ by a Teflon pad.


Subject(s)
Adhesives/administration & dosage , Gelatin Sponge, Absorbable/administration & dosage , Gelatin/administration & dosage , Hemifacial Spasm/surgery , Microvascular Decompression Surgery/methods , Vertebral Artery/surgery , Adult , Aged , Female , Hemifacial Spasm/diagnosis , Humans , Male , Middle Aged
11.
Med Mycol ; 59(8): 821-827, 2021 Jul 14.
Article in English | MEDLINE | ID: mdl-33626136

ABSTRACT

The present study reports the performance of the pigment hypericin (HYP)-loaded poloxamer-based mucoadhesive in situ gelling liquid crystalline precursor system (LCPS) for the treatment of vulvovaginal candidiasis (VVC) in mice. LCPS composed of 40% of ethoxylated and propoxylated cetyl alcohol, 30% of oleic acid and cholesterol (7:1), 30% of a dispersion of 16% poloxamer 407 and 0.05% of HYP (HYP-LCPS) was prepared and characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS) and ex vivo permeation and retention studies across vaginal porcine mucosa were performed. In addition, the antifungal properties of the HYP-LCPS were evaluated in a murine in vivo model; for this, infected C57BL female mice groups were treated with both HYP in solution and HYP-LCPS, and after 6 days colony forming unit (CFU)/ml count was performed. PLM and SAXS confirmed that HYP-LCPS is a microemulsion situated in boundary transition region confirming its action as an LCPS. When in contact with simulated vaginal fluid, HYP-LCPS became rigid and exhibited maltase crosses and bragg peaks characteristics of lamellar phase. Ex vivo permeation and retention studies showed that HYP-LCPS provides a localized treatment on the superficial layers of porcine vaginal mucosa. HYP-LCPS induced a significant reduction in the number of CFU/ml in the mice; thus this formulation indicated it is as effective as a commercial dosage form. It was concluded that LCPS maintains the biological activity of HYP and provides an adequate drug delivery system for this lipophilic molecule at the vaginal mucosa, being a promising option in cases of VVC.


Subject(s)
Anthracenes/administration & dosage , Antifungal Agents/administration & dosage , Candida albicans/drug effects , Candidiasis, Vulvovaginal/drug therapy , Perylene/analogs & derivatives , Vagina/metabolism , Adhesives/administration & dosage , Animals , Anthracenes/metabolism , Antifungal Agents/metabolism , Chromatography, High Pressure Liquid , Disease Models, Animal , Female , Mice , Mice, Inbred C57BL , Microscopy, Polarization , Mucous Membrane/metabolism , Mucous Membrane/microbiology , Mucous Membrane/pathology , Perylene/administration & dosage , Perylene/metabolism , Poloxamer/administration & dosage , Radiation-Sensitizing Agents , Scattering, Small Angle , Swine , Vagina/microbiology , Vagina/pathology , X-Ray Diffraction
12.
Mol Pharm ; 18(3): 1157-1166, 2021 03 01.
Article in English | MEDLINE | ID: mdl-33504154

ABSTRACT

Though pharmaceutical polymers were widely used in inhibiting drug recrystallization via strong intermolecular hydrogen and ionic bonds, the improved drug stability was achieved at the cost of the drug release rate or amount in the drug-in-adhesive transdermal patch. To overcame the difficulty, this study aimed to increase drug loading utilizing a novel drug-ionic liquid (drug-IL) strategy and illustrate the underlying molecular mechanism. Here, naproxen (NPX) and triamylamine (TAA) were chosen as the model drug and corresponding counterion, respectively. In addiiton, carboxylic pressure-sensitive adhesive (PSA) was chosen as the model polymer. The drug-IL (NPX-TAA) was synthesized and characterized by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), and proton nuclear magnetic resonance. The miscibility between NPX-TAA and PSA was assessed using microscopy study, X-ray diffraction, fluorescence spectroscopy, and solubility parameter calculation. In addition, molecular mechanisms of crystallization inhibition were revealed by FT-IR, Raman spectroscopy, DSC, X-ray photoelectron spectroscopy (XPS), and molecular docking. Finally, the release pattern of the high load patch of NPX-TAA was evaluated using in vitro drug release and verified by a skin permeation experiment. The results showed that drug loading in PSA was increased by 5.0 times, which was caused by the synergistic effect of strong ionic hydrogen bonding (the decreased intensity and blue shift of the O-H peak of COOH in PSA) formed between NPX-TAA and PSA-COO- and normal hydrogen bonding (red shift of the C═O peak in PSA) formed between NPX-TAA and the carbonyl group of PSA. In addition, -NH+ of TAA was confirmed as the molecular basis of ionic hydrogen bonding through new peak appearance (binding energy: 400.0 eV) in XPS spectra. Moreover, high drug release percent (80.8 ± 1.8%) was achieved even at high drug loading compared with the control group (72.4 ± 2.2%). Thus, this study introduced an effective drug-IL method to enhance drug loading capacity and illustrated the brand-new action mechanism, which provided a powerful instrument for the development of a high drug loading-high release patch.


Subject(s)
Adhesives/chemistry , Hydrogen/chemistry , Ionic Liquids/chemistry , Macrocyclic Compounds/chemistry , Adhesives/administration & dosage , Animals , Calorimetry, Differential Scanning/methods , Crystallization/methods , Drug Liberation/drug effects , Hydrogen Bonding/drug effects , Macrocyclic Compounds/administration & dosage , Molecular Docking Simulation/methods , Naproxen/administration & dosage , Naproxen/chemistry , Photoelectron Spectroscopy/methods , Polymers/chemistry , Rabbits , Skin/drug effects , Skin Absorption/drug effects , Solubility/drug effects , Spectroscopy, Fourier Transform Infrared/methods , Spectrum Analysis, Raman/methods , Transdermal Patch , X-Ray Diffraction/methods
13.
Chem Phys Lipids ; 235: 105052, 2021 03.
Article in English | MEDLINE | ID: mdl-33482099

ABSTRACT

Current study was aimed to design and develop muco-adhesive self-nano emulsifying drug delivery system (SNEDDs) for improved pharmacokinetics of Cefixime (CFX) in rabbits. The components of SNEDDs formulation i.e., cinnamon oil, Tween® 80, and PEG 200 as oil, surfactant, and co-surfactant respectively were selected based on their high solubilizing capability of the drug. SNEDDs formulation was optimized using Design of experiments (D-optimal design) in terms of droplet size, poly dispersity index and zeta potential. The optimized SNEDDs formulation was studied for various parameters like droplet size, morphology, zeta potential, emulsification, optical clarity, thermodynamic stability, GIT stability, and robustness to dilution. CFX was loaded to optimized formulation to form CFX-SNEDDs. Furthermore, acyl-chitosan, a muco-adhesive agent, was added to CFX-SNEDDS to prepare CHT-CFX-SNEDDS. In vitro drug release showed the controlled release behavior reached a maximum value of 70 % at pH 6.8 within 24 h. The droplet size, atomic force microscopy, and optical clarity analysis revealed the formation of nanosized emulsion (156 ± 25 nm) with spherical morphology. Also in vivo pharmacokinetic studies on rabbits showed an increased drug plasma concentration for CHT-CFX-SNEDDs (15 ± 3 µg/mL) and CFX-SNEDDs (9 ± 2 µg/mL) in comparison with control CFX (4 ± 1 µg/mL). The results indicated that the developed CHT-CFX-SNEDDs with an increased degree of solubilization, permeation, and nanosized range emulsion enhance the oral performance of CFX.


Subject(s)
Adhesives/pharmacokinetics , Cefixime/pharmacokinetics , Chitosan/chemistry , Drug Delivery Systems , Drug Development , Lipids/chemistry , Adhesives/administration & dosage , Adhesives/chemistry , Administration, Oral , Animals , Cefixime/administration & dosage , Cefixime/blood , Chitosan/chemical synthesis , Emulsions/chemistry , Male , Particle Size , Rabbits
14.
ACS Appl Bio Mater ; 4(6): 5016-5025, 2021 06 21.
Article in English | MEDLINE | ID: mdl-35007050

ABSTRACT

Hydrogel adhesives have been widely used in wet environments. Nonetheless, strong and stable persistent adhesion remains a challenge. Here, we report a facile yet powerful strategy to construct high-strength hydrogel adhesives for durable adhesion in a saline environment. Such a hydrogel consists of two polymer networks: a hydrophobic-associated polyacrylamide network of covalent and noncovalent cross-links and an alginate network cross-linked by divalent cations in saline. Meanwhile, polydopamine nanoparticles formed through in-situ self-polymerization are distributed evenly throughout the system to provide underwater adhesion. A low and controllable swelling rate and high compressive strength of hydrogels can be achieved via this multiple interaction strategy. Ultimately, this strategy contributes to the persistent underwater adhesion of hydrogels, and the decreasing rate of lap-shear adhesion strength of hydrogels is only 24.79 ± 8.01% after saline immersion for up to 21 days. Moreover, good cytocompatibility of hydrogels is helpful for their application in the biomedical field.


Subject(s)
Adhesives/chemistry , Hydrogels/chemistry , Acrylamide/chemistry , Acrylic Resins/chemistry , Adhesives/administration & dosage , Alginates/chemistry , Ammonium Sulfate/chemistry , Animals , Cell Line , Cell Survival/drug effects , Ethanolamines/chemistry , Humans , Hydrogels/administration & dosage , Indoles/administration & dosage , Indoles/chemistry , Methacrylates/chemistry , Mice , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Polymers/administration & dosage , Polymers/chemistry , Saline Solution/chemistry
15.
Drug Deliv ; 28(1): 87-99, 2021 Dec.
Article in English | MEDLINE | ID: mdl-33342321

ABSTRACT

Recurrent aphthous ulcer (RAU) is a well-known painful, inflammatory disease with uncertain etiology for which local symptomatic therapy is only available. The aim of this study was to formulate and characterize muco-adhesive sponges containing a mixture of tenoxicam and miconazole nitrate to manage pain, inflammation and avoid candida infection that may accompany RAU due to poor oral hygiene. Two polymers at different concentrations were used to prepare sponges applying simple freeze-drying. Medicated chitosan (2%) sponges (mC2) showed acceptable physical appearance, surface pH (6.3 ± 0.042), porosity (25.7% ± 1.8), swelling index (5.7 ± 0.11), in-vivo and ex-vivo muco-adhesion time (115 min.±0.813 and 155 min.±1.537, respectively), ex-vivo muco-adhesion force (0.09 N ± 0.002) and scanning electron microscope (SEM) images. For concurrent clear-cut determination of tenoxicam and miconazole nitrate from mC2, a new UPLC method was developed and validated. mC2 sponges exhibited superior in-vitro drug release profiles where ∼100% of tenoxicam released within 5 min for fast pain relief with a more prolonged miconazole nitrate release. Furthermore, in-vivo animal study revealed that mC2 caused a significant decrease in the acetic acid-induced ulcer size in rats after 6 days of treatment (p < .0001) compared to negative and positive controls. Additionally, histopathological examination showed faster healing with complete restoration of the normal oral histology in rats. The present study concludes that chitosan sponge loaded with a combination of tenoxicam and miconazole nitrate could improve healing of RAU cases.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Antifungal Agents/administration & dosage , Drug Carriers/chemistry , Miconazole/administration & dosage , Piroxicam/analogs & derivatives , Stomatitis, Aphthous/drug therapy , Adhesives/administration & dosage , Animals , Carboxymethylcellulose Sodium/chemistry , Chitosan/chemistry , Dose-Response Relationship, Drug , Drug Liberation , Freeze Drying , Hydrogen-Ion Concentration , Microscopy, Electron, Scanning , Piroxicam/administration & dosage , Rats , Wound Healing
16.
AAPS PharmSciTech ; 21(8): 297, 2020 Oct 25.
Article in English | MEDLINE | ID: mdl-33099696

ABSTRACT

The aim of this study was to develop a suitable drug-in-adhesive patch for transdermal delivery of koumine. Acrylic polymer Duro-Tak® 87-4287, which contains hydroxyl groups, may significantly enhance the skin permeation of koumine from transdermal patches containing 0.93-3.72% koumine. Among permeation enhancers, 10% azone showed the greatest potential and increased the flux of koumine to 1.48-fold that of the control. Therefore, an optimized patch formulation containing 3.72% koumine and 10% azone in Duro-Tak® 87-4287 that offers good physical properties was selected for an in vivo pharmacokinetic study using rats. The maximal plasma drug concentration (Cmax) of koumine after transdermal administration (4 mg/patch) was 25.80 ± 1.51 ng/mL, which was in the range of those after oral administration (3 mg/kg and 15 mg/kg). The time to the maximal concentration (Tmax) and the half-life (t1/2) of the drug with transdermal administration were 3.96 ± 0.46 h and 21.10 ± 1.36 h, respectively, which were longer than those with oral administration. Furthermore, the area under the concentration-time curve (AUC0-72 h) of 898.20 ± 45.57 ng·h/mL for the transdermal patch was much higher than that for oral administration (15 mg/kg). In conclusion, the drug-in-adhesive patch containing koumine provides a steady plasma koumine level and sustained release in vivo and can be an effective means of transdermal delivery for koumine.


Subject(s)
Adhesives/administration & dosage , Drug Compounding , Indole Alkaloids/chemistry , Indole Alkaloids/pharmacokinetics , Skin Absorption/drug effects , Administration, Cutaneous , Animals , Half-Life , Indole Alkaloids/administration & dosage , Male , Rats
17.
Spine (Phila Pa 1976) ; 45(22): 1598-1604, 2020 Nov 15.
Article in English | MEDLINE | ID: mdl-32756274

ABSTRACT

STUDY DESIGN: Observational study. OBJECTIVE: The aim of this study was to evaluate the accuracy of a new frameless reference marker system for patient tracking by analyzing the effect of vertebral position within the surgical field. SUMMARY OF BACKGROUND DATA: Most modern navigation systems for spine surgery rely on a dynamic reference frame attached to a vertebra for tracking the patient. This solution has the drawback of being bulky and obstructing the surgical field, while requiring that the dynamic reference frame is moved between vertebras to maintain accuracy. METHODS: An augmented reality surgical navigation (ARSN) system with intraoperative cone beam computed tomography (CBCT) capability was installed in a hybrid operating room. The ARSN system used input from four video cameras for tracking adhesive skin markers placed around the surgical field. The frameless reference marker system was evaluated first in four human cadavers, and then in 20 patients undergoing navigated spine surgery. In each CBCT, the impact of vertebral position in the surgical field on technical accuracy was analyzed. The technical accuracy of the inserted pedicle devices was determined by measuring the distance between the planned position and the placed pedicle device, at the bone entry point. RESULTS: The overall mean technical accuracy was 1.65 ±â€Š1.24 mm at the bone entry point (n = 366). There was no statistically significant difference in technical accuracy between levels within CBCTs (P ≥ 0.12 for all comparisons). Linear regressions showed that null- to negligible parts of the effect on technical accuracy could be explained by the number of absolute levels away from the index vertebrae (r ≤ 0.007 for all, ß ≤ 0.071 for all). CONCLUSION: The frameless reference marker system based on adhesive skin markers is unobtrusive and affords the ARSN system a high accuracy throughout the navigated surgical field, independent of vertebral position. LEVEL OF EVIDENCE: 3.


Subject(s)
Adhesives/administration & dosage , Augmented Reality , Cone-Beam Computed Tomography/methods , Neuronavigation/methods , Patient Identification Systems/methods , Surgery, Computer-Assisted/methods , Adolescent , Adult , Aged , Aged, 80 and over , Cadaver , Female , Humans , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Male , Middle Aged , Pedicle Screws , Sacrum/diagnostic imaging , Sacrum/surgery , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/surgery , Young Adult
18.
Carbohydr Polym ; 242: 116428, 2020 Aug 15.
Article in English | MEDLINE | ID: mdl-32564847

ABSTRACT

Mucoadhesive chitosan-based electrospun nanofibers are promising candidates for overcoming challenges associated with sublingual drug delivery, yet studies focusing on evaluating the mucoadhesive properties of nanofibers for sublingual administration are limited. The aim was to elucidate the mucoadhesive properties of chitosan/polyethylene oxide (PEO) nanofibers focusing on how the degree of deacetylation (DDA, 53-96 %) of chitosan influenced their morphological and mucoadhesive properties. The mechanism of mucoadhesion was explained by the intermolecular interactions of chitosan with mucin from bovine submaxillary glands using quartz-crystal microbalance with dissipation monitoring and by adhesion of the nanofibers to ex vivo porcine sublingual mucosa. An increase in chitosan DDA improved the morphological stability of the nanofibers in water, but did not contribute to altered mucoadhesive properties. This study demonstrates excellent mucoadhesive properties of chitosan/PEO nanofibers and shows that the strong mucoadhesiveness of the nanofibers is attributed to their swelling ability.


Subject(s)
Chitosan/chemistry , Mouth Mucosa/chemistry , Nanofibers/chemistry , Polyethylene Glycols/chemistry , Adhesives/administration & dosage , Adhesives/chemistry , Administration, Sublingual , Animals , Cattle , Chitosan/administration & dosage , Drug Delivery Systems , Mucins/chemistry , Nanofibers/administration & dosage , Polyethylene Glycols/administration & dosage , Submandibular Gland/chemistry
19.
Pharm Dev Technol ; 25(8): 989-998, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32397780

ABSTRACT

Preterm labor is the main cause of death and serious illness of both infants and pregnant women in Africa and worldwide. Parenteral and oral salbutamol sulfate as a B2 antagonist has been used for the treatment of preterm labor. The study aims are to formulate salbutamol sulfate non-invasive vaginal bioadhesive tablets to avoid the side effects of conventional formulations. Full factorial design 41 ×31 ×21 was used for the preparation of 24 vaginal bioadhesive tablet formulations. The independent factors were polymer type (Carbopol 934, HPMC 4000, HEC, and PEG 6000), polymer to drug ratio (1:1, 2:1, and 3:1), and diluent (lactose and mannitol). Vaginal bioadhesive tablets were evaluated for residence time and time required for release 50% of salbutamol sulfate T50% as dependent variables. The formulations were evaluated in terms of drug content, mass variation, hardness, friability, swelling index, residence time, and in-vitro drug release. Results revealed that polymer and diluent types are the most significant factors in both residence time and T50%. A strong positive correlation (0.91) between in-vitro and ex-vivo permeation was observed, which predict the best in-vivo performance of salbutamol vaginal bioadhesive tablet. Thus, salbutamol sulfate vaginal bioadhesive tablets could be a successful remedy for preterm labor.


Subject(s)
Adhesives/chemistry , Albuterol/chemistry , Obstetric Labor, Premature/prevention & control , Sulfates/chemistry , Vaginal Creams, Foams, and Jellies/chemistry , Adhesives/administration & dosage , Albuterol/administration & dosage , Chemistry, Pharmaceutical , Excipients/chemistry , Female , Hardness , Humans , Infant, Newborn , Polymers/chemistry , Pregnancy , Sulfates/administration & dosage , Vaginal Creams, Foams, and Jellies/administration & dosage
20.
Int J Pharm ; 581: 119293, 2020 May 15.
Article in English | MEDLINE | ID: mdl-32247812

ABSTRACT

Intraoral lidocaine formulations are applied in children and adults for pain relief. The potential risks associated with orally administered lidocaine due to accidental ingestions were highlighted in a warning letter by the US Food and Drug Administration (FDA). This increases the urgency for a need of a child-appropriate dosage forms. For risk minimization, a novel buccal composite dosage form was developed consisting of a lidocaine containing minitablet centered on top of a bilayered mucoadhesive buccal film, so called composite. The preparation included direct tableting of minitablets as well as film-casting technique. Within a comparability study, the permeation of this composite was classified against marketed lidocaine gel, a single-layer film, and a minitablet. These ex-vivo permeation studies under physiologically related conditions in combination with LC-MS/MS quantification enabled the evaluation of permeation in clinically relevant short-term application. The composite showed comparable permeation to marketed gel (104.26 ± 30.15 µg/cm2 vs 128.17 ± 12.49 µg/cm2 cumulative amount of drug) and a higher permeation compared to film (25.84 ± 6.01 µg/cm2). Therefore, a controlled drug application can be assumed by the composite, whereby the risk of inadvertent swallowing as well as uncontrolled absorbed amount of drug substance may be substantially minimized.


Subject(s)
Adhesives/metabolism , Anesthetics, Local/metabolism , Dosage Forms , Drug Development/methods , Lidocaine/metabolism , Mouth Mucosa/metabolism , Adhesives/administration & dosage , Anesthetics, Local/administration & dosage , Animals , Drug Evaluation, Preclinical/methods , Esophagus/drug effects , Esophagus/metabolism , Lidocaine/administration & dosage , Mouth Mucosa/drug effects , Organ Culture Techniques , Permeability/drug effects , Swine
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