scholarly journals Film-Forming Systems for the Delivery of DNDI-0690 to Treat Cutaneous Leishmaniasis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 516
Author(s):  
Katrien Van Bocxlaer ◽  
Kerri-Nicola McArthur ◽  
Andy Harris ◽  
Mo Alavijeh ◽  
Stéphanie Braillard ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cutaneous Leishmaniasis ◽  
Mouse Skin ◽  
Parasite Load ◽  
Leishmania Species ◽  
Lesion Size ◽  
Drying Time ◽  
Sustained Drug Delivery ◽  
Film Forming ◽  
The Impact

In cutaneous leishmaniasis (CL), parasites reside in the dermis, creating an opportunity for local drug administration potentially reducing adverse effects and improving treatment adherence compared to current therapies. Polymeric film-forming systems (FFSs) are directly applied to the skin and form a thin film as the solvent evaporates. In contrast to conventional topical dosage forms, FFSs strongly adhere to the skin, favouring sustained drug delivery to the affected site, reducing the need for frequent applications, and enhancing patient compliance. This study reports the first investigation of the use of film-forming systems for the delivery of DNDI-0690, a nitroimidazole compound with potent activity against CL-causing Leishmania species. A total of seven polymers with or without plasticiser were evaluated for drying time, stickiness, film-flexibility, and cosmetic attributes; three FFSs yielded a positive evaluation for all test parameters. The impact of each of these FFSs on the permeation of the model skin permeant hydrocortisone (hydrocortisone, 1% (w/v) across the Strat-M membrane was evaluated, and the formulations resulting in the highest and lowest permeation flux (Klucel LF with triethyl citrate and Eudragit RS with dibutyl sebacate, respectively) were selected as the FFS vehicle for DNDI-0690. The release and skin distribution of the drug upon application to Leishmania-infected and uninfected BALB/c mouse skin were examined using Franz diffusion cells followed by an evaluation of the efficacy of both DNDI-0690 FFSs (1% (w/v)) in an experimental CL model. Whereas the Eudragit film resulted in a higher permeation of DNDI-0690, the Klucel film was able to deposit four times more drug into the skin, where the parasite resides. Of the FFSs formulations, only the Eudragit system resulted in a reduced parasite load, but not reduced lesion size, when compared to the vehicle only control. Whereas drug delivery into the skin was successfully modulated using different FFS systems, the FFS systems selected were not effective for the topical application of DNDI-0690. The convenience and aesthetic of FFS systems alongside their ability to modulate drug delivery to and into the skin merit further investigation using other promising antileishmanial drugs.

scholarly journals Activity of Amphotericin B-Loaded Chitosan Nanoparticles against Experimental Cutaneous Leishmaniasis

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 4002
Author(s):  
Alaa Riezk ◽  
Katrien Van Bocxlaer ◽  
Vanessa Yardley ◽  
Sudaxshina Murdan ◽  
Simon L. Croft
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Amphotericin B ◽  
Leishmania Major ◽  
Chitosan Nanoparticles ◽  
Mouse Skin ◽  
Parasite Load ◽  
Lesion Size ◽  
Franz Diffusion Cells ◽  
Positively Charged

Chitosan nanoparticles have gained attention as drug delivery systems (DDS) in the medical field as they are both biodegradable and biocompatible with reported antimicrobial and anti-leishmanial activities. We investigated the application of chitosan nanoparticles as a DDS for the treatment of cutaneous leishmaniasis (CL) by preparing two types of chitosan nanoparticles: positively charged with tripolyphosphate sodium (TPP) and negatively charged with dextran sulphate. Amphotericin B (AmB) was incorporated into these nanoparticles. Both types of AmB-loaded nanoparticles demonstrated in vitro activity against Leishmania major intracellular amastigotes, with similar activity to unencapsulated AmB, but with a significant lower toxicity to KB-cells and red blood cells. In murine models of CL caused by L. major, intravenous administration of AmB-loaded chitosan-TPP nanoparticles (Size = 69 ± 8 nm, Zeta potential = 25.5 ± 1 mV, 5 mg/kg/for 10 days on alternate days) showed a significantly higher efficacy than AmBisome® (10 mg/kg/for 10 days on alternate days) in terms of reduction of lesion size and parasite load (measured by both bioluminescence and qPCR). Poor drug permeation into and through mouse skin, using Franz diffusion cells, showed that AmB-loaded chitosan nanoparticles are not appropriate candidates for topical treatment of CL.

scholarly journals Relation between Skin Pharmacokinetics and Efficacy in AmBisome Treatment of Murine Cutaneous Leishmaniasis

2017 ◽  
Vol 62 (3) ◽  
Author(s):  
Gert-Jan Wijnant ◽  
Katrien Van Bocxlaer ◽  
Vanessa Yardley ◽  
Andy Harris ◽  
Sudaxshina Murdan ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Parasite Load ◽  
Lesion Size ◽  
Clear Correlation ◽  
Relative Reduction ◽  
Multiple Dosing ◽  
Content Type ◽  
Drug Levels ◽  
Skin Pharmacokinetics

ABSTRACTAmBisome (LAmB), a liposomal formulation of amphotericin B (AmB), is a second-line treatment for the parasitic skin disease cutaneous leishmaniasis (CL). Little is known about its tissue distribution and pharmacodynamics to inform clinical use in CL. Here, we compared the skin pharmacokinetics of LAmB with those of the deoxycholate form of AmB (DAmB; trade name Fungizone) in murine models ofLeishmania majorCL. Drug levels at the target site (the localized lesion) 48 h after single intravenous (i.v.) dosing of the individual AmB formulations (1 mg/kg of body weight) were similar but were 3-fold higher for LAmB than for DAmB on day 10 after multiple administrations (1 mg/kg on days 0, 2, 4, 6, and 8). After single and multiple dosing, intralesional concentrations were 5- and 20-fold, respectively, higher than those in the healthy control skin of the same infected mice. We then evaluated how drug levels in the lesion after LAmB treatment relate to therapeutic outcomes. After five administrations of the drug at 0, 6.25, or 12.5 mg/kg (i.v.), there was a clear correlation between dose level, intralesional AmB concentration, and relative reduction in parasite load and lesion size (R2values of >0.9). This study confirms the improved efficacy of the liposomal over the deoxycholate AmB formulation in experimental CL, which is related to higher intralesional drug accumulation.

Hydrophobic and Hydrophilic Film-Forming Gels for the Controlled Delivery of Drugs with Different Levels of Hydrophobicity

2020 ◽  
Vol 21 ◽  
Author(s):  
Khanh T. Nguyen ◽  
Phuong H.L. Tran ◽  
Hai V. Ngo ◽  
Thao T.D. Tran
Keyword(s):  
Sustained Release ◽  
Hydroxypropyl Methylcellulose ◽  
Controlled Delivery ◽  
Drying Time ◽  
Terbinafine Hydrochloride ◽  
Sustained Drug Delivery ◽  
Film Forming ◽  
Wide Range ◽  
Highly Hydrophobic ◽  
Different Levels

Background: This study aimed to evaluate the effects of hydrophobic and hydrophilic film-forming gels (FFGs) on the controlled delivery of drugs with different levels of hydrophobicity. Methods: This evaluation was carried out by employing zein and polyvinylpyrrolidone as hydrophobic and hydrophilic film-forming agents, respectively, in combination with hydroxypropyl methylcellulose functionalized as a hydrogel basement at a ratio that had been optimized to achieve the fastest drying time. Free curcumin or terbinafine hydrochloride was subsequently dispersed into blank FFGs to produce the final FFG formulations. Results: Although the extreme hydrophobicity of curcumin strongly limited its topical permeability compared to that of terbinafine hydrochloride, zein FFGs clearly resulted in a favourable sustained release system for highly hydrophobic drugs, such as curcumin. Moreover, polyvinylpyrrolidone would be highly effective for the sustained release of a less hydrophobic drug, such as terbinafine hydrochloride. Analyses of the wettability, surface morphology, chemical interactions and crystallinity of FFGs also helped to elucidate the mechanisms of their drug release profiles. Conclusion: This fundamental finding is beneficial for further design studies on FFGs as sustained drug delivery systems for topical drugs with a wide range of hydrophobicities.

FABRICATION AND EVALUATION OF CHITOSAN-BASED FILM FORMING GEL OF ACECLOFENAC FOR TRANSDERMAL DRUG DELIVERY

INDIAN DRUGS ◽  
2021 ◽  
Vol 58 (06) ◽  
pp. 68-70
Author(s):  
Himani Bajaj ◽  
◽  
Vinod Singh ◽  
Ranjit Singh ◽  
Tirath Kumar ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Methyl Cellulose ◽  
Tween 80 ◽  
Thickness Variation ◽  
Prepared Film ◽  
Polyethylene Glycol 400 ◽  
Drying Time ◽  
Variable Effect ◽  
Peg 400 ◽  
Film Forming

The objective of the present study was to prepare a topical film-forming gel of aceclofenac for the treatment of rheumatic diseases, using a safe and effective drug delivery approach. Aceclofenac film-forming gels were prepared using hydroxypropyl methyl cellulose and chitosan polymeric blend in varying concentrations, polyethylene glycol 400 (PEG 400) as a plasticizer, Tween 80 as a permeation enhancer and ethanol as solvent. The prepared film-forming gels were evaluated and the influence of the concentration and ratio of polymeric blends, plasticizer, and ethanol used were investigated. All the prepared film-forming gels showed satisfactory properties regarding consistency, spreadability and thickness. Variation in the concentration of polymers, ethanol and PEG 400 showed a variable effect on drying time from film-forming gels. Film-forming gels of aceclofenac were successfully developed and may provide a promising effective formulation that may improve patient compliance.

scholarly journals Topical Treatment for Cutaneous Leishmaniasis: Dermato-Pharmacokinetic Lead Optimization of Benzoxaboroles

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Katrien Van Bocxlaer ◽  
Eric Gaukel ◽  
Deirdre Hauser ◽  
Seong Hee Park ◽  
Sara Schock ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Skin Permeation ◽  
Mouse Skin ◽  
Topical Administration ◽  
Lesion Size ◽  
Drug Formulation ◽  
Content Type

ABSTRACTCutaneous leishmaniasis (CL) is caused by several species of the protozoan parasiteLeishmania, affecting an estimated 10 million people worldwide. Previously reported strategies for the development of topical CL treatments have focused primarily on drug permeation and formulation optimization as the means to increase treatment efficacy. Our approach aims to identify compounds with antileishmanial activity and properties consistent with topical administration. Of the test compounds, five benzoxaboroles showed potent activity (50% effective concentration [EC50] < 5 μM) against intracellular amastigotes of at least oneLeishmaniaspecies and acceptable activity (20 μM < EC50< 30 μM) against two more species. Benzoxaborole compounds were further prioritized on the basis of thein vitroevaluation of progression criteria related to skin permeation, such as the partition coefficient and solubility. An MDCKII-hMDR1 cell assay showed overall good permeability and no significant interaction with the P-glycoprotein transporter for all substrates except LSH002 and LSH031. The benzoxaboroles were degraded, to some extent, by skin enzymes but had stability superior to that ofpara-hydroxybenzoate compounds, which are known skin esterase substrates. Evaluation of permeation through reconstructed human epidermis showed LSH002 to be the most permeant, followed by LSH003 and LSH001. Skin disposition studies following finite drug formulation application to mouse skin demonstrated the highest permeation for LSH001, followed by LSH003 and LSH002, with a significantly larger amount of LSH001 than the other compounds being retained in skin. Finally, the efficacy of the leads (LSH001, LSH002, and LSH003) againstLeishmania majorwas testedin vivo. LSH001 suppressed lesion growth upon topical application, and LSH003 reduced the lesion size following oral administration.

Plantago Ovata and Locust Bean Gum as a Natural Polymer in Hydrodynamically Balanced Systems: A Review

2020 ◽  
Author(s):  
Ghildiyal s
Keyword(s):  
Drug Delivery ◽  
Locust Bean Gum ◽  
Main Role ◽  
Natural Polymer ◽  
Release Formulation ◽  
Sustained Drug Delivery ◽  
Modern Drug ◽  
Buccal Drug Delivery ◽  
Locust Bean ◽  
Ceratonia Siliqua L

Hydrodynamically Balanced systems have wide development as they have achieved the parameters of modern drug delivery system, it is a type of system which owes very tremendous and curative benefits for the delivery of oral controlled release dosage forms and have wide properties in many aspects such as its main role is to maintain the effective concentration in the system for longer period of time. To reduce the gastric mucosal irritation due to the presence of synthetic polymers, being a natural polymer incorporation of Plantago ovate (Psyllium Husk) could ease out the mucosal irritation in the gastric region. Due to its properties such as a rate-controlling polymer possessing a very good quality of swelling and good gelling nature, and also incorporated as a matrix-forming agent basically in the modified release formulation. Locust bean gum can be used as sustained-release carriers and release modifiers for the delivery of drugs. It is a neutral plant galactomannan extracted from the seeds (kernels) of the carob tree Ceratonia siliqua L fabaceae. Nowadays it is focussing polymer and a lot of researchers are focussing on exploring the potential in topical drug delivery, colonic drug delivery, oral sustained drug delivery, ocular drug delivery, buccal drug delivery.

Carbon Nanotubes, Quantum Dots and Dendrimers as Potential Nanodevices for Nanotechnology Drug Delivery Systems

2013 ◽  
Vol 6 (3) ◽  
pp. 2113-2124
Author(s):  
Prashant Malik ◽  
Neha Gulati ◽  
Raj Kaur Malik ◽  
Upendra Nagaich
Keyword(s):  
Carbon Nanotubes ◽  
Drug Delivery ◽  
Quantum Dots ◽  
Self Assembly ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Atomic Scale ◽  
Sustained Drug Delivery ◽  
Pharmaceutical Nanotechnology ◽  
Conventional Device

Nanotechnology deal with the particle size in nanometers. Nanotechnology is ranging from extensions of conventional device physics to completely new approaches based upon molecular self assembly, from developing new materials with dimensions on the nanoscale to direct control of matter on the atomic scale. In nanotechnology mainly three types of nanodevices are described: carbon nanotubes, quantum dots and dendrimers. It is a recent technique used as small size particles to treat many diseases like cancer, gene therapy and used as diagnostics. Nanotechnology used to formulate targeted, controlled and sustained drug delivery systems. Pharmaceutical nanotechnology embraces applications of nanoscience to pharmacy as nanomaterials and as devices like drug delivery, diagnostic, imaging and biosensor materials. Pharmaceutical nanotechnology has provided more fine tuned diagnosis and focused treatment of disease at a molecular level.    

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