Rheological and Drug Delivery Characteristics of Poloxamer-Based Diclofenac Sodium Formulations for Chronic Wound Site Analgesia

Jackson Russo; Jennifer Fiegel; Nicole K. Brogden

doi:10.3390/pharmaceutics12121214

Rheological and Drug Delivery Characteristics of Poloxamer-Based Diclofenac Sodium Formulations for Chronic Wound Site Analgesia

Pharmaceutics ◽

10.3390/pharmaceutics12121214 ◽

2020 ◽

Vol 12 (12) ◽

pp. 1214

Author(s):

Jackson Russo ◽

Jennifer Fiegel ◽

Nicole K. Brogden

Keyword(s):

Drug Delivery ◽

Chronic Wounds ◽

Chronic Wound ◽

Diclofenac Sodium ◽

Barrier Properties ◽

Poloxamer 407 ◽

Tape Stripping ◽

Gelation Temperature ◽

Wound Site ◽

Topical Dosage

Chronic wounds are a significant and growing health problem, and clinical treatment is often a painful experience. A topical dosage form would be optimal to treat this pain. Poloxamer 407, a thermosensitive polymer that is a liquid at low temperatures but gels at higher temperatures, is well suited to administer topical analgesics to chronic wound sites. The goal of this study was to evaluate the gelation and drug delivery properties of poloxamer 407 gels containing diclofenac sodium for potential use in chronic wound analgesic delivery. The gelation properties of poloxamer formulations were evaluated rheologically. Drug delivery properties of poloxamers loaded with diclofenac sodium were evaluated using snakeskin dialysis membranes, intact porcine ear skin, and porcine ear skin impaired via tape stripping. A commercial gel product and a solution of diclofenac sodium in water were used as control formulations. Poloxamer concentration and gelation temperature varied inversely, and the addition of higher concentrations of diclofenac sodium correlated to significant increases in poloxamer gelation temperature. Poloxamer solutions were effective in limiting the permeation of diclofenac sodium through membranes with impaired barrier properties, and delivery of diclofenac sodium from poloxamer 407 did not vary significantly from delivery observed from the commercial gel product. The amount of drug delivered in 24 h did not change significantly with changes in poloxamer 407 concentration. The results of this study indicate that poloxamer 407 may be a useful formulation component for administration of an analgesic product to a chronic wound site.

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Innovations in drug delivery for chronic wound healing

Current Pharmaceutical Design ◽

10.2174/1381612827666210714102304 ◽

2021 ◽

Vol 27 ◽

Author(s):

Erfan Rezvani Ghomi ◽

Mohamadreza Shakiba ◽

Ali Saedi Ardahaei ◽

Mahsa Akbari ◽

Mehdi Faraji ◽

...

Keyword(s):

Drug Delivery ◽

Wound Healing ◽

Drug Delivery Systems ◽

Chronic Wounds ◽

Chronic Wound ◽

Healing Process ◽

Skin Structure ◽

Physical Problems ◽

Complex Process ◽

Chronic Ulcers

: Wound healing is a varied and complex process designed to promptly restore standard skin structure, function, and appearance. To achieve this goal, different immune and biological systems participate in coordination through four separate steps, including homeostasis, inflammation, proliferation, and regeneration. Each step involves the function of other cells, cytokines, and growth factors. However, chronic ulcers, which are classified into three types of ulcers, namely vascular ulcers, diabetic ulcers, and pressure ulcers, cannot heal through the mentioned natural stages. It causes mental and physical problems for these people and, as a result, imposes high economic and social costs on society. In this regard, using a system that can accelerate the healing process of such chronic wounds, as an urgent need in the community, should be considered. Therefore, in this study, the innovations of drug delivery systems for the healing of chronic wounds using hydrogels, nanomaterial, and membranes are discussed and reviewed.

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The Rheolaser Master™ and Kinexus Rotational Rheometer® to Evaluate the Influence of Topical Drug Delivery Systems on Rheological Features of Topical Poloxamer Gel

Molecules ◽

10.3390/molecules25081979 ◽

2020 ◽

Vol 25 (8) ◽

pp. 1979

Author(s):

Maria Chiara Cristiano ◽

Francesca Froiio ◽

Antonia Mancuso ◽

Federica De Gaetano ◽

Cinzia Anna Ventura ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Three Dimensional ◽

Delivery Systems ◽

Water Soluble ◽

Poloxamer 407 ◽

Viscoelastic Parameter ◽

Rotational Rheometer ◽

Water Soluble Drugs ◽

Topical Dosage

Poloxamer 407 copolymer is a versatile and widely used thermo-reversible material. Its use has many advantages, such as bio-adhesion, enhanced solubilization of poorly water-soluble drugs and many applications fields like oral, rectal, topical, nasal drug administration. Hydrogels made up of Poloxamer 407 are characterized by specific rheological features, which are affected by temperature, concentration and presence of other compounds. A strategic approach in topical therapeutic treatments may be the inclusion of drug delivery systems, such as ethosomes, transfersomes and niosomes, into hydrogel poloxamer formulation. The evaluation of the interaction between colloidal carriers and the Poloxamer 407 hydrogel network is essential for a suitable design of an innovative topical dosage form. For this reason, the Rheolaser Master™, based on diffusing wave spectroscopy, and a Kinexus Rotational Rheometer were used to evaluate the influence of nanocarriers on the microrheological features of hydrogels. The advantages of the Rheolaser Master™ analyzer are: (i) its ability to determine viscoelastic parameter, without altering or destroying the sample and at rest (zero shear); (ii) possibility of aging analysis on the same sample. This study provide evidence that vesicular systems do not influence the rheological features of the gel, supporting the possibility to encapsulate an innovative system into a three-dimensional network.

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ID3015 Mesenchymal stem cells for treatment of chronic wounds: A Study with autologous transplantation of adipose-derived stem cells

Biomedical Research and Therapy ◽

10.15419/bmrat.v4is.236 ◽

2017 ◽

Vol 4 (S) ◽

pp. 27

Author(s):

Han Van Dinh

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Chronic Wounds ◽

Chronic Wound ◽

Autologous Transplantation ◽

Adipose Derived Stem Cells ◽

Fibroblast Proliferation ◽

Wound Site ◽

And Migration ◽

Proliferation And Migration

Objective: This study was to determine the effects of adipose-derived stem cells (ADSCs) on dermal fibroblasts responses to injury including migration and proliferation in vitro. We also evaluated the autologous transplantation of ADSCs on treatment of human chronic wounds. Subjects and methods: The proliferation and migration of fibroblast was evaluated by co-culture ADSCs with allogenic dermal fibroblast and by the scratch assay. In clinical study, autologous ADSCs were transplanted on to chronic wounds of 25 patients, who were hospitalized into the Wound Healing Department of the National Institute of Burns from April, 2015 to June, 2016. The mean age was 56.88 ± 16.81, male/female ratio was 2.12. The autologous adipose-derived stem cells at passages 5 were transplanted on surface of wound every 3÷5 days. The wound biopsies for H&E staining and for Transmission Electron Microscope were taken before transplantation and at day 7, day15 and day 20 of studied progress. Results: ADSCs stimulated fibroblast proliferation and migration in wound healing assay. In clinical study, before transplantation, extracellular matrix (ECM) was destroyed. After transplantation, ADSCs strongly stimulated fibroblast proliferation and fibroblasts to produce collagen. ADSCs also promoted proliferations of epithelial cells and neovascularization at the chronic wound site. Conclusion: Autologous ADSCs promoted the wound healing process by cell proliferation and improvement of ECM in chronic wound site.

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Thermosensitive Gels Used to Improve Microneedle-Assisted Transdermal Delivery of Naltrexone

Polymers ◽

10.3390/polym13060933 ◽

2021 ◽

Vol 13 (6) ◽

pp. 933

Author(s):

Kevin V. Tobin ◽

Jennifer Fiegel ◽

Nicole K. Brogden

Keyword(s):

Drug Delivery ◽

Aqueous Solution ◽

Transdermal Delivery ◽

Release Kinetics ◽

Poloxamer 407 ◽

Gelation Temperature ◽

Before And After ◽

Application Frequency

Transdermal delivery of naltrexone (NTX) can be enhanced using microneedles, although micropores generated this way can reseal by 48 h in humans, which prevents further drug delivery from a formulation. Poloxamer 407 (P407) is a thermosensitive polymer that may extend microneedle-assisted NTX delivery time by creating an in situ gel depot in the skin. We characterized gelation temperature, drug release, and permeation of P407 gels containing 7% NTX-HCl. To investigate microneedle effects on NTX-HCl permeation, porcine skin was treated with microneedles (600 or 750 μm length), creating 50 or 100 micropores. The formulations were removed from the skin at 48 h to simulate the effect of micropores resealing in vivo, when drug delivery is blunted. Gelation temperature increased slightly with addition of NTX-HCl. In vitro NTX-HCl release from P407 formulations demonstrated first order release kinetics. Microneedle treatment enhanced NTX-HCl permeation both from aqueous solution controls and P407 gels. Steady-state flux was overall lower in the P407 conditions compared to the aqueous solution, though ratios of AUCs before and after gel removal demonstrate that P407 gels provide more sustained release even after gel removal. This may be beneficial for reducing the required application frequency of microneedles for ongoing treatment.

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Exploring Dendrimer Nanoparticles for Chronic Wound Healing

Frontiers in Medical Technology ◽

10.3389/fmedt.2021.661421 ◽

2021 ◽

Vol 3 ◽

Author(s):

Samuel Tetteh-Quarshie ◽

Eric R. Blough ◽

Cynthia B. Jones

Keyword(s):

Drug Delivery ◽

Wound Healing ◽

Drug Delivery Systems ◽

Chronic Wounds ◽

Chronic Wound ◽

Treatment Options ◽

The United States ◽

Delivery Systems ◽

Infection Age ◽

Nanoparticle Drug Delivery

The United States spends billions of dollars to treat chronic wounds each year. Wound healing is complex in nature which involves several intricate multiphase processes that can be delayed for a number of reasons leading to the development of chronic wounds. Wound healing therapies range from topical preparations to surgical repair with treatment options that vary based on other underlying factors like co-infection, age, or co-morbidities such as diabetes. Historically, micelles and liposomes are some of the nanoparticle drug delivery systems explored to treat chronic wounds; however, recent data suggests that dendrimers have shown potential to rival these systems in treating chronic wounds as well as other diseases. This mini review examines advances in dendrimer nanoparticle drug delivery systems to treat chronic wounds.

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Experience of using atraumatic ointment bandages based on peruvian balsam in the complex treatment of patients with chronic wound defects of the lower limbs

Hirurg (Surgeon) ◽

10.33920/med-15-2002-05 ◽

2020 ◽

pp. 43-57

Author(s):

Anna Tabuika

Keyword(s):

Diabetes Mellitus ◽

Staphylococcus Aureus ◽

Chronic Wounds ◽

Chronic Wound ◽

Local Treatment ◽

Lower Limbs ◽

Complex Treatment ◽

Average Area ◽

Arterial Insufficiency ◽

Significant Activation

The article reflects the results of a retrospective non-comparative study, the objects of which were 34 outpatient comorbid patients (15 of which are over 60 years old) with chronic wounds of the lower limbs developed against the background of varicosity, post-thrombotic disease, chronic arterial insufficiency of the lower limbs, diabetes mellitus or their combination. Their local treatment was carried out using atraumatic ointment dressing «Branolind N» containing Peruvian balsam. There were 23 women (67.6 %) and 11 men (32.4 %). In microbiological study prior to the beginning of treatment in 31 patients the growth of a pathogen of wound infection was revealed; in 19 patients — Staphylococcus aureus in monoculture and in various associations, in 6 patients — Pseudomonas aeruginosa in monoculture, in other cases — other pathogens. In 3 patients the pathogen was not detected. The average wound size was 34 cm2 . The phase of the wound process was additionally confirmed by cytological studies. After treatment the average area of the wound defect decreased by 10 cm2 and made 24 cm2 on average. Full healing of the wound defect occurred in 11 patients, the others had granulation and active marginal epithelization. There was also a decrease in bacterial semination of wounds, a change in composition of infection agents to less aggressive monoflora, and cytologically — a decrease in signs of inflammation against the background of significant activation of reparative processes.

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Natural, Synthetic and their Combinatorial Nanocarriers Based Drug Delivery System in the Treatment Paradigm for Wound Healing Via Dermal Targeting

Current Pharmaceutical Design ◽

10.2174/1381612826666200612164511 ◽

2020 ◽

Vol 26 (36) ◽

pp. 4551-4568

Author(s):

Mohammad Kashif Iqubal ◽

Sadaf Saleem ◽

Ashif Iqubal ◽

Aiswarya Chaudhuri ◽

Faheem Hyder Pottoo ◽

...

Keyword(s):

Drug Delivery ◽

Wound Healing ◽

Photodynamic Therapy ◽

Growth Factors ◽

Combination Therapy ◽

Healing Process ◽

Wound Healing Process ◽

Wound Site ◽

Synthetic Drugs ◽

Treatment Paradigm

A wound refers to the epithelial loss, accompanied by loss of muscle fibers collagen, nerves and bone instigated by surgery, trauma, frictions or by heat. Process of wound healing is a compounded activity of recovering the functional integrity of the damaged tissues. This process is mediated by various cytokines and growth factors usually liberated at the wound site. A plethora of herbal and synthetic drugs, as well as photodynamic therapy, is available to facilitate the process of wound healing. Generally, the systems used for the management of wounds tend to act through covering the ruptured site, reduce pain, inflammation, and prevent the invasion and growth of microorganisms. The available systems are, though, enough to meet these requirements, but the involvement of nanotechnology can ameliorate the performance of these protective coverings. In recent years, nano-based formulations have gained immense popularity among researchers for the wound healing process due to the enhanced benefits they offer over the conventional preparations. Hereupon, this review aims to cover the entire roadmap of wound healing, beginning from the molecular factors involved in the process, the various synthetic and herbal agents, and combination therapy available for the treatment and the current nano-based systems available for delivery through the topical route for wound healing.

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Topical Lipid Based Drug Delivery Systems for Skin Diseases: A Review

Current Drug Therapy ◽

10.2174/1574885513666181112153213 ◽

2020 ◽

Vol 15 (4) ◽

pp. 283-298

Author(s):

Suresh Kumar Sahu ◽

Rakesh Raj ◽

Pooja Mongia Raj ◽

Ram Alpana

Keyword(s):

Drug Delivery ◽

Skin Diseases ◽

Topical Therapy ◽

Skin Layer ◽

Dosage Forms ◽

Delivery Systems ◽

Systemic Side Effects ◽

Transcutaneous Delivery ◽

Topical Dosage ◽

Topical Dosage Forms

Treatment of skin ailments through systemic administration is limited due to toxicity and patients discomfort. Hence, lower risk of systemic side effects from topical dosage forms like ointments, creams, emulsions and gels is more preferred for the treatment of skin disease. Application of lipid based carriers in drug delivery in topical formulations has recently become one of the major approaches to improve drug permeation, safety, and effectiveness. These delivery systems include liposomes, ethosomes, transfersomes, Nanoemulsions (NEs), Solid Lipid Nanoparticles (SLNs) Nanostructured Lipid Carriers (NLCs) and micelles. Most of the liposomes and SLNs based products are in the market while some are under investigation. Transcutaneous delivery of therapeutics to the skin layer by novel lipid based carriers has enhanced topical therapy for the treatment of skin ailments. This article covers an overview of the lipid-based carriers for topical uses to alleviate skin diseases.

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Fluorescent Imaging and Precise Suppression of Bacterial Infection in Chronic Wounds by Porphyrin-Based Metal-Organic Framework Nanorod

Journal of Materials Chemistry B ◽

10.1039/d1tb01649k ◽

2021 ◽

Author(s):

zhen zou ◽

Lihua Zhang ◽

Minzhi Ouyang ◽

Yufei Zhang ◽

Huanxiang Wang ◽

...

Keyword(s):

Bacterial Infection ◽

Antibacterial Agents ◽

Chronic Wounds ◽

Chronic Wound ◽

Metal Organic Framework ◽

Critical Role ◽

Fluorescent Imaging ◽

Wound Management ◽

Metal Organic ◽

Chronic Wound Management

Nano-antibacterial agents play a critical role in chronic wound management. However, an intelligent nanosystem that can provide both visual warning of infection and precise sterilization remains a hurdle. Herein, a...

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