Design and Evaluation of a Poly(Lactide-co-Glycolide)-Based In Situ Film-Forming System for Topical Delivery of Trolamine Salicylate

Trolamine salicylate (TS) is a topical anti-inflammatory analgesic used to treat small joint pain. The topical route is preferred over the oral one owing to gastrointestinal side effects. In this study, a poly(lactide-co-glycolide) (PLGA)-based in situ bio-adhesive film-forming system for the transdermal delivery of TS was designed and evaluated. Therefore, varying amounts (0%, 5%, 10%, 20%, and 25% (w/w)) of PLGA (EXPANSORB® DLG 50-2A, 50-5A, 50-8A, and 75-5A), ethyl 2-cyanoacrylate, poly (ethylene glycol) 400, and 1% of TS were dissolved together in acetone to form the bio-adhesive polymeric solution. In vitro drug permeation studies were performed on a vertical Franz diffusion cell and dermatomed porcine ear skin to evaluate the distinct formulations. The bio-adhesive polymeric solutions were prepared successfully and formed a thin film upon application in situ. A significantly higher amount of TS was delivered from a formulation containing 20% PLGA (45 ± 4 µg/cm2) and compared to PLGA-free counterpart (0.6 ± 0.2 µg/cm2). Furthermore, the addition of PLGA to the polymer film facilitated an early onset of TS delivery across dermatomed porcine skin. The optimized formulation also enhanced the delivery of TS into and across the skin.

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Novel Design Approaches in the Fabrication of Polymeric Microarray Patches via Micromoulding

Micromachines ◽

10.3390/mi11060554 ◽

2020 ◽

Vol 11 (6) ◽

pp. 554 ◽

Cited By ~ 2

Author(s):

Inken Ramöller ◽

Emma McAlister ◽

Abigail Bogan ◽

Ana Cordeiro ◽

Ryan Donnelly

Keyword(s):

Skin Barrier ◽

Systemic Delivery ◽

Porcine Skin ◽

Density Maps ◽

In Vitro Permeation ◽

Wide Range ◽

Significant Difference ◽

Permeation Studies ◽

Novel Design

The focus on novel systems for transdermal delivery of therapeutic agents has increased considerably over recent years, as this administration route comes with many advantages. Polymeric microarray patches (MAPs) are minimally invasive devices that enable systemic delivery of a wide range of drugs by overcoming the outer skin barrier. Conventionally, MAPs fabricated by micromoulding have a low needle density. In this study, the performance of hydrogel-forming MAPs cast using novel industrially manufactured micromoulds with a high needle density (600 needles/0.75 cm2) was compared to that of MAPs obtained using conventional moulds with a lower density (196 needles/0.89 cm2). Surrounding holders for micromoulds were designed for time-efficient fabrication of MAPs. The influence of needle densities on mechanical strength, insertion efficiency and in vitro permeation of ibuprofen sodium (IBU) was analysed. Insertion of both MAPs into an artificial skin model and neonatal porcine skin was comparable. No significant difference was observed in permeation studies of IBU (p > 0.05), with a delivery of 8.7 ± 1.7 mg for low-density and 9.5 ± 0.1 mg for high-density MAPs within 24 h. This highlights the potential of these novel micromoulds for manufacturing polymeric MAPs with a higher needle density for future applications.

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A bioactive hyaluronic acid–based hydrogel cross-linked by Diels–Alder reaction for promoting neurite outgrowth of PC12 cells

Journal of Bioactive and Compatible Polymers ◽

10.1177/0883911516684654 ◽

2017 ◽

Vol 32 (4) ◽

pp. 382-396 ◽

Cited By ~ 3

Author(s):

Dongming Xing ◽

Lie Ma ◽

Changyou Gao

Keyword(s):

Hyaluronic Acid ◽

Ethylene Glycol ◽

Neurite Outgrowth ◽

Pc12 Cells ◽

Alder Reaction ◽

Poly Ethylene Glycol ◽

Substitution Degree ◽

Poly Ethylene

In order to improve neurite outgrowth on the in situ formed hyaluronic acid–based hydrogel, furan and methacrylate groups were grafted on hyaluronic acid successively. Furthermore, a laminin-derived peptide CQAASIKVAV was covalently immobilized via the Michael addition. The furan- and peptide-modified hyaluronic acid was then cross-linked in situ by mixing with bismaleimide poly(ethylene glycol) at 37 °C to obtain a bioactive hyaluronic acid–based hydrogel. The hyaluronic acid derivatives were characterized by 1H NMR and Fourier transform infrared spectroscopy. The gelation, swelling, and mechanical property of the hydrogels were analyzed. The modulus of the hydrogel could be tuned by changing furan substitution degree, while the peptide concentration could be changed by the ratio of furan- and peptide-modified hyaluronic acid with hyaluronic acid–furan. In vitro culture of PC12 cells showed that the longest neurite outgrowth appeared on the hyaluronic acid–poly(ethylene glycol) hydrogel with the highest peptide content (the substitution degree of peptide in furan- and peptide-modified hyaluronic acid was 23 %) and a lower threshold modulus of 4.5 kPa. The furan and methacrylate-functionalized hyaluronic acid provides a versatile platform for diverse functionalization and can be used for modulation of other cell behaviors as well.

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In-Situ Gelling System based on Thiolated Gellan Gum as New Carrier for Nasal Administration of Dimenhydrinate

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2009.2.2.8 ◽

2009 ◽

Vol 2 (2) ◽

pp. 544-550

Author(s):

Hitendra Mahajan ◽

Hannan Shaikh ◽

Surendra Gattani ◽

Pankaj Nerkar

Keyword(s):

Nasal Mucosa ◽

Histopathological Examination ◽

Polymer Concentration ◽

Gellan Gum ◽

Nasal Administration ◽

In Vitro Permeation ◽

Permeation Studies ◽

In Situ Gelling

The purpose of the present study was to develop intranasal delivery system of dimenhydrinate using thiolated gellan gum and formulations were modulated so as to have gelation at physiological ion content after intranasal administration. Gelation was determined by physical appearance. The mucoadhesive force in terms of detachment stress, determined using sheep nasal mucosa, increased with increasing concentration of thiolated polymer. The results of in vitro drug permeation studies across sheep nasal mucosa indicate that effective permeation could be significantly increased by using in situ gelling formulation with thiolated polymer concentration. Finally, histopathological examination did not detect any changes during in vitro permeation studies. In conclusion the gel formulation of dimenhydrinate with in situ gelling and mucoadhesive properties with increased permeation rate is promising for prolonging nasal residence time and thereby nasal absorption.

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Oral Administration of Chemotherapeutic Agents Using Complexation Hydrogels

MRS Proceedings ◽

10.1557/proc-724-n10.4 ◽

2002 ◽

Vol 724 ◽

Cited By ~ 1

Author(s):

James Blanchette ◽

Kinam Park ◽

Nicholas A Peppas

Keyword(s):

Small Intestine ◽

Intestinal Epithelium ◽

Chemotherapeutic Agents ◽

Uv Spectrophotometry ◽

Ph Responsive ◽

Poly Ethylene Glycol ◽

Target Delivery ◽

Poly Ethylene

AbstractCarriers were synthesized to target delivery of a chemotherapeutic agent, bleomycin, to the upper small intestine in response to the pH shift when entering the upper small intestine from the stomach. Complexation hydrogels capable of pH-responsive swelling were used to form these carriers. Hydrogel nanospheres composed of methacrylic acid (MAA) and poly(ethylene glycol) (PEG) were loaded with bleomycin. Loading of bleomycin was performed by in situ polymerization and release of bleomycin from the nanospheres was measured by UV spectrophotometry. Results showed that bleomycin release from the nanospheres was responsive to the pH of the environment surrounding the nanospheres. In addition to pH-responsive release of bleomycin, the hydrogel nanospheres are also able to enhance the permeability of an in vitro model of the intestinal epithelium. Increasing the permeability of the intestinal epithelium could aid in transport of bleomycin from the lumen of the small intestine out into the bloodstream.

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Delivery of ethinylestradiol from film forming polymeric solutions across human epidermis in vitro and in vivo in pigs

Journal of Controlled Release ◽

10.1016/j.jconrel.2006.12.013 ◽

2007 ◽

Vol 118 (2) ◽

pp. 196-203 ◽

Cited By ~ 39

Author(s):

Ines Zurdo Schroeder ◽

Patrick Franke ◽

Ulrich F. Schaefer ◽

Claus-Michael Lehr

Keyword(s):

Human Epidermis ◽

Film Forming ◽

Polymeric Solutions

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A New Approach to Ex Vivo Permeation Studies in In-Situ Film-Forming Systems

AAPS PharmSciTech ◽

10.1208/s12249-020-01799-6 ◽

2020 ◽

Vol 21 (7) ◽

Author(s):

Amanda F. Silva-Alvarez ◽

Maíra P. Ferreira ◽

Fabiana T. M. C. Vicentini ◽

Vinicius Pedrazzi ◽

Osvaldo de Freitas

Keyword(s):

Ex Vivo ◽

New Approach ◽

Ex Vivo Permeation ◽

Film Forming ◽

Permeation Studies

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Effect of Hydroxyapatite-Tricalcium Phosphate Micro-Particles on the Cellular Interaction of In Situ Hyaluronic Acid-Poly(Ethylene Oxide) Hydrogel

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.342-343.765 ◽

2007 ◽

Vol 342-343 ◽

pp. 765-768

Author(s):

Mi Sook Kim ◽

Yoon Jeong Choi ◽

Gun Woo Kim ◽

In Sup Noh ◽

Yong Doo Park ◽

...

Keyword(s):

Hyaluronic Acid ◽

Ethylene Oxide ◽

Tricalcium Phosphate ◽

Particle Surface ◽

Cellular Interaction ◽

Micro Particles ◽

Poly Ethylene Oxide ◽

Poly Ethylene

In vitro cell behaviors of calvarial osteoblasts (MC3T3) were evaluated by seeding them on both the surface and inside of in situ hyaluronic acid-poly(ethylene oxide) (HA-PEO) hydrogel, either after or before incorporation of mixture micro-particles of hydroxyapatite-β-tricalcium phosphate on/inside the hydrogel, respectively. Cellular behaviors such as adhesion and proliferation on the surface and inside the gel were evaluated with light microscopy and a microplate reader by focusing on the interactions of cell-HA-PEO as well as cell-hydroxyapatitetricalcium phosphate micro-particle surface in the gel. Cell adhesion and spreading seemed to be enhanced by supplying the micro-particles to the inside the HA-PEO hydrogel, compared to the results of the HA-PEO hydrogel itself.

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Hp--CD-VoriconazoleIn SituGelling System for Ocular Drug Delivery:In Vitro, Stability, and Antifungal Activities Assessment

BioMed Research International ◽

10.1155/2013/341218 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 27

Author(s):

Pravin Pawar ◽

Heena Kashyap ◽

Sakshi Malhotra ◽

Rakesh Sindhu

Keyword(s):

Sodium Alginate ◽

Drug Content ◽

Polymeric Carriers ◽

Antifungal Efficiency ◽

Ophthalmic Delivery ◽

Permeation Studies ◽

Stability Data ◽

The Stability

The objective of the present study was to design ophthalmic delivery systems based on polymeric carriers that undergo sol-to-gel transition upon change in temperature or in the presence of cations so as to prolong the effect of HP-β-CD Voriconazole (VCZ)in situgelling formulations. Thein situgelling formulations of Voriconazole were prepared by using pluronic F-127 (PF-127) or with combination of pluronic F-68 (PF-68) and sodium alginate by cold method technique. The prepared formulations were evaluated for their physical appearance, drug content, gelation temperature (),in vitropermeation studies, rheological properties, mucoadhesion studies, antifungal studies, and stability studies. All batches ofin situformulations had satisfactory pH ranging from 6.8 to 7.4, drug content between 95% and 100%, showing uniform distribution of drug. As the concentration of each polymeric component was increased, that is, PF-68 and sodium alginate, there was a decrease in with increase in viscosity and mucoadhesive strength. Thein vitrodrug release decreased with increase in polymeric concentrations. The stability data concluded that all formulations showed the low degradation and maximum shelf life of 2 years. The antifungal efficiency of the selected formulation againstCandida albicansandAsperigillus fumigatusconfirmed that designed formulation has prolonged effect and retained its properties against fungal infection.

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DESIGNING OF NOVEL TOPICAL IN SITU POLYMERIC FILM-FORMING SOLUTION SPRAY FORMULATION OF ANTIFUNGAL AGENT: IN VITRO ACTIVITY AND IN VIVO CHARACTERIZATION

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2022v14i1.43581 ◽

2022 ◽

pp. 169-184

Author(s):

NABIL ABDULLAH ◽

AMIT B. PATIL

Keyword(s):

Ex Vivo ◽

Skin Irritation ◽

Inhibition Zone ◽

Wistar Rat ◽

Polymeric Film ◽

Film Forming ◽

Spray Formulation

Objective: Voriconazole (VCZ) is a broad-spectrum antifungal medication that works by inhibiting fungal Cytochrome P450, preventing fungi growth. The current study aims at developing and characterizing an antifungal in situ film-forming polymeric solution spray containing VCZ for use in topical drug delivery systems. Methods: Optimized VCZ in situ polymeric film formulation was evaluated for Fourier transform infrared spectroscopy (FTIR), differential scanning calorimeter (DSC), X-ray diffractometry (XRD), Scanning electron microscope (SEM), in vitro and in vivo, ex-vivo investigation using abdominal rat skin and stability studies. The in vivo antifungal activity of the advanced in situ film was examined in albino Wistar rats. Results: The optimized batch contained 22% Eudragit RS 100 (ERS) and 4% Sorbitol. Based on FTIR, XRD, SEM, and rheological studies. Formulation ingredients of VCZ loaded topical in situ polymeric film spray were observed to be compatible and showed no evidence of precipitation, deformation, or discoloration. Diffusion test (in vitro %), and ex-vivo drug diffusion % obtained 99.22%, and 97.45% respectively. The maximum inhibition zone was measured at 13±0.07 mm. The Wistar rat was employed as an animal model for skin irritation and antifungal studies. A study of short-term stability observed no significant modifications in the physical properties. Conclusion: The findings of the optimized VCZ topical in situ polymeric film spray formulation were satisfactory, demonstrating comparable improvement in superficial antifungal treatment.

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