Ion Pair Strategy in Solid Lipid Nanoparticles: a Targeted Approach to Improve Epidermal Targeting with Controlled Adapalene Release, Resulting Reduced Skin Irritation

Rodrigues, Linna B O; Lima, Flávia Alves; Alves, Camila Priscila Barbosa; Martins-Santos, Elisângela; Aguiar, Marta Maria Gontijo De; Oliveira, Cleida A.; Oréfice, Rodrigo Lambert; Ferreira, Lucas Antônio Miranda; Goulart, Gisele Assis Castro

doi:10.1007/s11095-020-02866-0

Cited by 12 publications

(19 citation statements)

References 38 publications

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“… 2020 ; Rodrigues et al. 2020 ). Additionally, for partition coefficient, compared to CA, CA-ODA conjugates exhibited significant improvement in lipophilicity ( Figure 2(c) ).…”

Section: Resultsmentioning

confidence: 99%

Chondroitin sulfate-functionalized lipid nanoreservoirs: a novel cartilage-targeting approach for intra-articular delivery of cassic acid for osteoarthritis treatment

et al. 2022

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Novel intra-articular nanoreservoirs were implemented employing different cartilage targeting approaches to improve cartilage bioavailability of a chondroprotective drug, cassic acid (CA), for effective amelioration of cartilage deterioration off-targeting CA gastrointestinal disorders. Herein, we compared active cartilage-targeting approach via chondroitin sulfate (CHS) functionalization versus passive targeting using positively charged nanoparticles to target negatively charged cartilage matrix. Firstly, CA integrated nanoreservoirs (CA-NRs) were fabricated based on ionic conjugation between CA and cationic hydrophobic surface modifier octadecylamine (ODA) and were further functionalized with CHS to develop CHS-CA-NRs. Confocal laser microscope was used to visualize the accumulation of nanoparticles into the cartilage tissue. Both targeting approaches promoted CA local cartilage availability and prolonged its residence time. Compared to passive targeted CA-NRs, active targeted CHS-CA-NRs showed higher fluorescence signals in proximity to and inside chondrocytes which lasted for up to 21 days. In MIA-osteoarthritic rats, CHS-CA-NRs showed superior antiosteoarthritic activity, exhibiting highest cartilage repair compared to CA-NRs. Additionally, CHS-CA-NRs significantly inhibited OA inflammatory cytokine, degradation enzyme and oxidative stress and improved cartilage matrix biosynthesis. Conclusively, CHS-CA-NRs improved OA repair showing a superior efficacy for articular cartilage targeting with CHS which could be a potential advance for OA therapy.

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“… 2020 ; Rodrigues et al. 2020 ). Additionally, for partition coefficient, compared to CA, CA-ODA conjugates exhibited significant improvement in lipophilicity ( Figure 2(c) ).…”

Section: Resultsmentioning

confidence: 99%

Chondroitin sulfate-functionalized lipid nanoreservoirs: a novel cartilage-targeting approach for intra-articular delivery of cassic acid for osteoarthritis treatment

et al. 2022

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“…In our studies with fluconazole (Ayub et al., 2007), ∼10% and ∼5%‐11% of the applied dose was quantified in the epidermis and dermis, respectively, for the different emulsions evaluated. In studies with tretinoin (Lima et al., 2021), ∼0.6% and ∼20.5% of the applied dose was quantified in the epidermis and dermis, respectively; and in studies with adapalene (Rodrigues et al., 2020), ∼1.2% and ∼16.4% of the applied dose was quantified in the epidermis and dermis, respectively. The dose applied to each membrane is calculated by subtracting from the average dose (determined during dose standardization) the amount of formulation retained on the glass swab.…”

Section: Strategic Planningmentioning

confidence: 99%

“…To achieve this, various solubility modifiers, such as surfactants, inorganic salts, and organic co‐solvents, are routinely added to aqueous dissolution media (Phillips, Pygall, Cooper, & Mann, 2012). In our studies with retinoids, we used a receptor fluid composed of a mixture of 90:10 (v/v) PBS, pH 7.4/ethanol containing 2% (w/v) polysorbate 60, to guarantee the presence of the sink condition for the studied drugs, adapalene (Rodrigues et al., 2020) and tretinoin (Lima et al., 2021). Ethanol affects the phase behavior of lipid membranes as a function of concentration, but no significant effect is observed when the aqueous dispersion phase contains 10% ethanol (Kwak et al., 2012).…”

Section: Strategic Planningmentioning

confidence: 99%

Stepwise Protocols for Preparation and Use of Porcine Ear Skin for in Vitro Skin Permeation Studies Using Franz Diffusion Cells

et al. 2022

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The skin, the largest organ of the body, is an attractive route of topical and systemic drug administration. During the development of topical formulations, in vitro skin permeation studies using biological membranes mounted in Franz diffusion cells are a useful tool to assess the permeation of substances through the skin, and are recommended by the Organization for Economic Cooperation and Development (OECD). Among the types of biological membranes used in such studies, porcine ear skin has been identified as the most promising, due to its similarities to human skin and its greater accessibility as compared to human skin. To standardize techniques for the preparation and use of porcine ear skin as biological membrane, here we present systematic procedures for the selection of porcine ears, their cleaning, the removal of skin from cartilage, its transformation into membranes, and its use for the in vitro assessment of the permeation of drugs from topical formulations. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Obtaining porcine ear membranes Basic Protocol 2: Preparation of membranes from porcine ear skin and use of membranes for in vitro skin permeation studies

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“…Recently, ion pairing was used in a novel fashion by Rodrigues and co-workers to increase the lipophilicity of the hydrophobic drug, adapalene [ 53 ]. This molecule has been used for the topical treatment of acne.…”

Section: Ion Pairsmentioning

confidence: 99%

“…While both compounds (i.e., adapalene and stearylamine) were considered practically insoluble in water, the interaction between these two molecular entities appeared to ensure that adapalene did not partition out of the lipid phase. Furthermore, the SLP formulation resulted in 4-fold more adapalene in the epidermis (16.36 ± 1.79 compared to 4.08 ± 0.22 µg cm −2 ) and 7-fold more retention in the dermis (1.17 ± 0.12 compared to 0.16 ± 0.03 µg cm −2 ), than the marketed gel formulation (0.1% w / w AD), in a porcine skin permeation study [ 53 ].…”

Section: Ion Pairsmentioning

confidence: 99%

Ion Pairs for Transdermal and Dermal Drug Delivery: A Review

et al. 2021

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Ion pairing is a strategy used to increase the permeation of topically applied ionised drugs. Formation occurs when the electrostatic energy of attraction between oppositely charged ions exceeds their mean thermal energy, making it possible for them to draw together and attain a critical distance. These ions then behave as a neutral species, allowing them to partition more readily into a lipid environment. Partition coefficient studies may be used to determine the potential of ions to pair and partition into an organic phase but cannot be relied upon to predict flux. Early researchers indicated that temperature, size of ions and dielectric constant of the solvent system all contributed to the formation of ion pairs. While size is important, this may be outweighed by improved lipophilicity of the counter ion due to increased length of the carbon chain. Organic counter ions are more effective than inorganic moieties in forming ion pairs. In addition to being used to increase permeation, ion pairs have been used to control and even prevent permeation of the active ingredient. They have also been used to stabilise solid lipid nanoparticle formulations. Ion pairs have been used in conjunction with permeation enhancers, and permeation enhancers have been used as counter ions in ion pairing. This review attempts to show the various ways in which ion pairs have been used in drug delivery via the skin. It also endeavours to extract and consolidate common approaches in order to inform future formulations for topical and transdermal delivery.

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Ion Pair Strategy in Solid Lipid Nanoparticles: a Targeted Approach to Improve Epidermal Targeting with Controlled Adapalene Release, Resulting Reduced Skin Irritation

Cited by 12 publications

References 38 publications

Chondroitin sulfate-functionalized lipid nanoreservoirs: a novel cartilage-targeting approach for intra-articular delivery of cassic acid for osteoarthritis treatment

Chondroitin sulfate-functionalized lipid nanoreservoirs: a novel cartilage-targeting approach for intra-articular delivery of cassic acid for osteoarthritis treatment

Stepwise Protocols for Preparation and Use of Porcine Ear Skin for in Vitro Skin Permeation Studies Using Franz Diffusion Cells

Ion Pairs for Transdermal and Dermal Drug Delivery: A Review

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