Physicochemical and pharmacokinetic parameters in drug selection and loading for transdermal drug delivery

Chandrashekar, N. S.; Rani, RH Shobha

doi:10.4103/0250-474x.40340

Cited by 87 publications

(56 citation statements)

References 2 publications

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“…[38] Passive transdermal delivery, however, is limited to small molecules (ideally < 500 Da) with octanol-water partition coefficients (log P) between 1 and 4. [39] Therefore, large hydrophilic molecules including many therapeutic proteins and peptides such as insulin demonstrate negligible permeation through the skin. To improve skin penetrability, physical/chemical enhancers such as electricity, ultrasound, microneedles, dimethyl sulfoxide (DMSO), urea, azone, pyrrolidones, alcohols, oils, and fatty acids are often used.…”

Section: Discussionmentioning

confidence: 99%

Transdermal Protein Delivery Using Choline and Geranate (CAGE) Deep Eutectic Solvent

Banerjee

Ibsen

Iwao

et al. 2017

Adv Healthcare Materials

171

155

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Transdermal delivery of peptides and other biological macromolecules is limited due to skin's inherent low permeability. Here, the authors report the use of a deep eutectic solvent, choline and geranate (CAGE), to enhance topical delivery of proteins such as bovine serum albumin (BSA, molecular weight: ≈66 kDa), ovalbumin (OVA, molecular weight: ≈45 kDa) and insulin (INS, molecular weight: 5.8 kDa). CAGE enhances permeation of BSA, OVA, and insulin into porcine skin ex vivo, penetrating deep into the epidermis and dermis. Studies using tritium-labeled BSA and fluorescein isothiocyanate labeled insulin show significantly enhanced delivery of proteins into and across porcine skin, penetrating the skin in a time-dependent manner. Fourier transform IR spectra of porcine stratum corneum (SC) samples before and after incubation in CAGE show a reduction in peak area attributed to SC lipid content, suggesting lipid extraction from the SC. Circular dichroism confirms that CAGE does not affect insulin's secondary conformation. In vivo studies in rats show that topical application of 10 U insulin dispersed in CAGE (25 U kg −1 insulin dose) leads to a highly significant 40% drop in blood glucose levels in 4 h that is relatively sustained for 12 h. Taken together, these studies demonstrate that CAGE is a promising vehicle for transdermal delivery of therapeutic proteins; specifically, as a noninvasive delivery alternative to injectable insulin for the treatment of diabetes.

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Section: Discussionmentioning

confidence: 99%

Transdermal Protein Delivery Using Choline and Geranate (CAGE) Deep Eutectic Solvent

Banerjee

Ibsen

Iwao

et al. 2017

Adv Healthcare Materials

171

155

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“…The published range of ideal partition coefficient values of drugs considered good candidates for transdermal permeation is 0.1-10 000 (i.e. a log P from À1 to 4) (Chandrashekar & Shobha Rani, 2008), indicating that 5-FU has an appropriate partition coefficient value for transdermal delivery.…”

Section: -Fu Partition Coefficient Determinationmentioning

confidence: 99%

Enhancement in deposition and permeation of 5-fluorouracil through human epidermis assisted by peptide dendrimers

et al. 2013

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Enhancing the deposition and permeation of 5-fluorouracil across human epidermis assisted by appropriately charged and well-defined peptide dendrimers was investigated. Peptide dendrimers with arginine as the terminal amino acid and having a range of terminal positive charges (4þ and 16 þ ) were synthesized by solid phase peptide synthesis. Various parameters including effect of peptide dendrimers on the solubility and partition coefficient of 5-FU, degradation of drug in skin as well as deposition and permeation of 5-FU in/through skin were studied. All the tested dendrimers increased the aqueous solubility and partition coefficient of 5-FU with each also significantly (p50.05) enhancing the deposition and permeation of 5-FU in/across human epidermis in a concentration-dependent manner. Of the three peptide dendrimers examined, R8 dendrimer (bearing 8 þ charge derived from four terminal arginines and MW of &1000 Da) showed greatest values for flux, Q 48 (cumulative amount of drug permeated at the end of 48 h) and amount of drug retained in human skin. Furthermore, this study also scrutinized and reports on the likely mechanisms by which peptide dendrimers act as transdermal permeation enhancers.

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“…According to Naik et al (8), in order to allow for skin permeation, an API must have an aqueous solubility of at least 1 mg/ml, a molecular weight below 500 Da, a melting point below 200°C, and a partition coefficient (log P) between 1 and 3 (8). The values referred to by Naik et al are not absolute values but merely give an indication of the optimal range of values, for example, Chandrashekar and Rani (9) reference values of molecular weight below 400, log P (octanol-water) between −1.0 and 4. Due to the introduction of various methods for enhancing skin permeation, new frontiers are being reached daily and the abovementioned values are constantly shifting.…”

Section: Introductionmentioning

confidence: 99%

Topical Delivery of 5-Fluorouracil from Pheroid™ Formulations and the In Vitro Efficacy Against Human Melanoma

et al. 2015

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Abstract. Drug delivery vehicles can influence the topical delivery and the efficacy of an active pharmaceutical ingredient (API). In this study, the influence of Pheroid™ technology, which is a unique colloidal drug delivery system, on the skin permeation and antimelanoma efficacy of 5-fluorouracil were investigated. Lotions containing Pheroid™ with different concentrations of 5-fluorouracil were formulated then used in Franz cell skin diffusion studies and tape stripping. The in vitro efficacy of 5-fluorouracil against human melanoma cells (A375) was investigated using a flow cytometric apoptosis assay. Statistically significant concentrations of 5-fluorouracil diffused into and through the skin with Pheroid™ formulations resulting in an enhanced in vitro skin permeation from the 4.0% 5-fluorouracil lotion (p<0.05). The stratum corneum-epidermis and epidermis-dermis retained 5-fluorouracil concentrations of 2.31 and 6.69 μg/ml, respectively, after a diffusion study with the 4.0% Pheroid™ lotion. Subsequent to the apoptosis assay, significant differences were observed between the effect of 13.33 μg/ml 5-fluorouracil in Pheroid™ lotion and the effects of the controls. The results obtained suggest that the Pheroid™ drug delivery system possibly enhances the flux and delivery of 5-fluorouracil into the skin. Therefore, using Pheroid™ could possibly be advantageous with respect to topical delivery of 5-fluorouracil.

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Physicochemical and pharmacokinetic parameters in drug selection and loading for transdermal drug delivery

Cited by 87 publications

References 2 publications

Transdermal Protein Delivery Using Choline and Geranate (CAGE) Deep Eutectic Solvent

Transdermal Protein Delivery Using Choline and Geranate (CAGE) Deep Eutectic Solvent

Enhancement in deposition and permeation of 5-fluorouracil through human epidermis assisted by peptide dendrimers

Topical Delivery of 5-Fluorouracil from Pheroid™ Formulations and the In Vitro Efficacy Against Human Melanoma

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