Polycaprolactone - Vitamin E TPGS micelles for delivery of paclitaxel: In vitro and in vivo evaluation.

This study aimed to present findings on a paclitaxel (PTX)-loaded polymeric micellar formulation based on polycaprolactone-vitamin E TPGS (PCL-TPGS) and evaluate its in vitro anticancer activity as well as its in vivo pharmacokinetic profile in healthy mice in comparison to a marketed formulation. Micelles were prepared by a co-solvent evaporation method. The micelle's average diameter and polydispersity were determined using dynamic light scattering (DLS) technique. Drug encapsulation efficiency was assessed using an HPLC assay. The in vitro cytotoxicity was performed on human breast cancer cells (MCF-7 and MDA-MB-231) using MTT assay. The in vivo pharmacokinetic profile was characterized following a single intravenous dose of 4 mg/kg to healthy mice. The mean diameters of the prepared micelles were ≤ 100 nm. Moreover, these micelles increased the aqueous solubility of PTX from ∼0.3 µg/mL to reach nearly 1 mg/mL. While the PTX-loaded micelles showed an in vitro cytotoxicity comparable to the marketed formulation (Ebetaxel), drug-free PCL-TPGS micelles did not show any cytotoxic effects on both types of breast cancer cells (∼100% viability). Pharmacokinetics of PTX as part of PCL-TPGS showed a significant increase in its volume of distribution compared to PTX conventional formulation, Ebetaxel, which is in line with what was reported for clinical nano formulations of PTX, i.e., Abraxane, Genexol-PM, or Apealea. The findings of our studies indicate a significant potential for PCL-TPGS micelles to act as an effective system for solubilization and delivery of PTX.

Development of Gefitinib-Loaded Solid Lipid Nanoparticles for the Treatment of Breast Cancer: Physicochemical Evaluation, Stability, and Anticancer Activity in Breast Cancer (MCF-7) Cells.

In the current study, the toxic effects of gefitinib-loaded solid lipid nanoparticles (GFT-loaded SLNs) upon human breast cancer cell lines (MCF-7) were investigated. GFT-loaded SLNs were prepared through a single emulsification-evaporation technique using glyceryl tristearate (Dynasan™ 114) along with lipoid® 90H (lipid surfactant) and Kolliphore® 188 (water-soluble surfactant). Four formulae were developed by varying the weight of the lipoid™ 90H (100-250 mg), and the GFT-loaded SLN (F4) formulation was optimized in terms of particle size (472 ± 7.5 nm), PDI (0.249), ZP (-15.2 ± 2.3), and EE (83.18 ± 4.7%). The optimized formulation was further subjected for in vitro release, stability studies, and MTT assay against MCF-7 cell lines. GFT from SLNs exhibited sustained release of the drug for 48 h, and release kinetics followed the Korsmeyer-Peppas model, which indicates the mechanism of drug release by swelling and/or erosion from a lipid matrix. When pure GFT and GFT-SLNs were exposed to MCF-7 cells, the activities of p53 (3.4 and 3.7 times), caspase-3 (5.61 and 7.7 times), and caspase-9 (1.48 and 1.69 times) were enhanced, respectively, over those in control cells. The results suggest that GFT-loaded SLNs (F4) may represent a promising therapeutic alternative for breast cancer.

Lipid-based nanoformulation optimization for achieving cutaneous targeting: Niosomes as the potential candidates to fulfill this aim.

The present study screened the utility of topically-applied nanoformulations to target the drugs/actives into the skin reservoir with the reduction of possible systemic absorption. The lipid-based nanoformulations selected in this study included solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), nanoemulsions (NEs), liposomes, and niosomes. We loaded flavanone and retinoic acid (RA) as the penetrants. The prepared nanoformulations were assessed for their average diameter, polydispersity index (PDI), and zeta potential. An in vitro permeation test (IVPT) was utilized to determine the skin delivery into/across pig skin, atopic dermatitis (AD)-like mouse skin, and photoaged mouse skin. We found an increased skin absorption of lipid nanoparticles following the increase of solid lipid percentage in the formulations (SLNs > NLCs > NEs). The use of liposomes even reduced the dermal/transdermal selectivity (S value) to lessen the cutaneous targeting. The niosomes resulted in significantly greater RA deposition and reduced permeation in the Franz cell receptor compared to the other nanoformulations. The S value of the RA delivery via stripped skin was increased by 26-fold in the niosomes compared to the free RA. The dye-labeled niosomes displayed a strong fluorescence in the epidermis and upper dermis through the visualization of fluorescence and confocal microscopies. The cyanoacrylate skin biopsy manifested greater hair follicle uptake of the niosomes compared to the free penetrants by 1.5 to three-fold. The 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay indicated an increase in antioxidant ability from 55% to 75% after flavanone entrapment in the niosomes. In the activated keratinocytes, the niosomal flavanone could suppress the overexpressed CCL5 to the baseline control because of the facile cell internalization. After the formulation optimization, the niosomes with higher phospholipid amount had a superior effect in delivering penetrants into the skin reservoir, with limited permeation to the receptors.

Nanoencapsulation of Tea Catechins for Enhancing Skin Absorption and Therapeutic Efficacy.

Tea catechins are a group of flavonoids that show many bioactivities. Catechins have been extensively reported as a potential treatment for skin disorders, including skin cancers, acne, photoaging, cutaneous wounds, scars, alopecia, psoriasis, atopic dermatitis, and microbial infection. In particular, there has been an increasing interest in the discovery of cosmetic applications using catechins as the active ingredient because of their antioxidant and anti-aging activities. However, active molecules with limited lipophilicity have difficulty penetrating the skin barrier, resulting in low bioavailability. Nevertheless, topical application is a convenient method for delivering catechins into the skin. Nanomedicine offers an opportunity to improve the delivery efficiency of tea catechins and related compounds. The advantages of catechin-loaded nanocarriers for topical application include high catechin loading efficiency, sustained or prolonged release, increased catechin stability, improved bioavailability, and enhanced accumulation or targeting to the nidus. Further, various types of nanoparticles, including liposomes, niosomes, micelles, lipid-based nanoparticles, polymeric nanoparticles, liquid crystalline nanoparticles, and nanocrystals, have been employed for topical catechin delivery. These nanoparticles can improve catechin permeation via close skin contact, increased skin hydration, skin structure disorganization, and follicular uptake. In this review, we describe the catechin skin delivery approaches based on nanomedicine for treating skin disorders. We also provide an in-depth description of how nanoparticles effectively improve the skin absorption of tea catechins and related compounds, such as caffeine. Furthermore, we summarize the possible future applications and the limitations of nanocarriers for topical delivery at the end of this review article.

Empirical Monetary Valuation of a Quality-Adjusted Life-Year in the Kingdom of Saudi Arabia: A Willingness-to-Pay Analysis.

BACKGROUND: No willingness-to-pay (WTP) per quality-adjusted life-year (QALY) value exists for the Kingdom of Saudi Arabia (KSA). OBJECTIVE: The primary objective of this study was to determine the WTP for a QALY in the KSA. METHODS: Adult citizens of the KSA, patients with cancer, or members of the general public (MGP) were recruited to participate in a time trade-off survey to elicit health utilities. Cancer was chosen as the disease of interest for patients and the MGP, with a scenario describing stage 3 colorectal cancer, because it is a disease condition that impacts on both quality of life and survival time. In a second step, respondents were asked about their WTP to move from the estimated health state to a state of perfect health for 1 year (QALY). Finally, that amount was processed to generate the WTP for a full QALY. The second step was repeated with a 5-year horizon. Sensitivity analyses were performed without outliers. RESULTS: From 400 participants, data from 378 subjects were obtained and usable: 177 patients, 201 MGP; 278 male, 100 female subjects; 231 aged 26-65 years. Demographic distribution varied widely between the two subgroups for age, education level, and employment status, but with less variation in sex and income. Elicited health utilities were 0.413 (0.472 after adjustment) for the overall group, 0.316 (0.416) for patients, and 0.499 (0.508) for MGP. Overall WTP for a QALY was $US25,600 (adjusted $US32,000) for the 1-year horizon and $US19,200 (adjusted $US22,720) for the 5-year horizon. CONCLUSION: This was the first empirical attempt to estimate the WTP per QALY for the KSA. Results are comparable to those in some other countries and to gross domestic product figures for the KSA. Further research in a country-wide sample is warranted.

Naphtho[1,2-b]furan-4,5-dione is a potent anti-MRSA agent against planktonic, biofilm and intracellular bacteria.

AIM: Naphtho[1,2-b]furan-4,5-dione (N12D) and naphtho[2,3-b]furan-4,9-dione (N23D) are furanonaphthoquinone derivatives from natural resources. We examined the antimicrobial activity of N12D and N23D against drug-resistant Staphylococcus aureus. MATERIALS & METHODS: Minimum inhibitory concentration, minimum bactericidal concentration, bacterial viability and agar diffusion assay were conducted against methicillin-resistant S. aureus (MRSA) and clinical isolates of vancomycin-resistant S. aureus. RESULTS & CONCLUSION: The minimum inhibitory concentration of N12D and N23D against MRSA was 4.9-9.8 and 39 µM, respectively. With regard to the agar diffusion test, the inhibition zone of the quinone compounds was threefold larger than that of oxacillin. N12D was found to inhibit MRSA biofilm thickness from 24 to 16 µm as observed by confocal microscopy. N12D showed a significant reduction of the intracellular MRSA burden without decreasing the macrophage viability. The antibacterial mechanisms of N12D may be bacterial wall/membrane damage and disturbance of gluconeogenesis and the tricarboxylic acid cycle.

Injectable Drug-Loaded Nanocarriers for Lung Cancer Treatments.

Different types of injectable nanoparticles, including metallic nanoparticles, polymeric nanocarriers, dendrimers, liposomes, niosomes, and lipid nanoparticles, have been employed to load drugs for lung delivery. Nanoparticles used for lung delivery offer some benefits over conventional formulations, including increased solubility, enhanced stability, improved epithelium permeability and bioavailability, prolonged half-life, tumor targeting, and minimal side effects. In recent years, the concept of using injectable nanocarriers as vehicles for drug delivery has attracted increasing attention. This review highlights recent developments using nanomedical approaches for drug targeting to the lungs. We systematically introduce the concepts and amelioration mechanisms of the nanomedical techniques for lung cancer therapy. Passive targeting by modulating the nanoparticulate structure and the physicochemical properties is an option for efficient drug delivery to the lungs. In addition, active targeting such as antibody or peptide conjugation to nanoparticles is another efficient way to deliver the drugs to the targeted site. This review describes various nanocarriers loaded with anticancer drugs for passive or active targeting of lung malignancy. In this review, we principally focus on the nanomedical application in animal studies. The article excludes investigations limited to cell-based experiments. The review ends by anticipating future developments and trends.

Prediction of Chlamydia pneumoniae protein localization in host mitochondria and cytoplasm and possible involvements in lung cancer etiology: a computational approach.

Collecting evidence suggests that the intercellular infection of Chlamydia pneumoniae in lungs contributes to the etiology of lung cancer. Many proteins of Chlamydia pneumoniae outmanoeuvre the various system of the host. The infection may regulate various factors, which can influence the growth of lung cancer in affected persons. In this in-silico study, we predict potential targeting of Chlamydia pneumoniae proteins in mitochondrial and cytoplasmic comportments of host cell and their possible involvement in growth and development of lung cancer. Various cellular activities are controlled in mitochondria and cytoplasm, where the localization of Chlamydia pneumoniae proteins may alter the normal functioning of host cells. The rationale of this study is to find out and explain the connection between Chlamydia pneumoniae infection and lung cancer. A sum of 183 and 513 proteins were predicted to target in mitochondria and cytoplasm of host cell out of total 1112 proteins of Chlamydia pneumoniae. In particular, many targeted proteins may interfere with normal growth behaviour of host cells, thereby altering the decision of program cell death. Present article provides a potential connection of Chlamydia pneumoniae protein targeting and proposed that various targeted proteins may play crucial role in lung cancer etiology through diverse mechanisms.

Cationic amphiphile in phospholipid bilayer or oil-water interface of nanocarriers affects planktonic and biofilm bacteria killing.

A cationic amphiphile, soyaethyl morpholinium ethosulfate (SME), immobilized in liposomes or nanoemulsions, was prepared in an attempt to compare the antibacterial activity between SME intercalated in the phospholipid bilayer and oil-water interface. Before antibacterial assessment, the size of the liposomes and nanoemulsions was respectively recorded as 75 and 214 nm. The data of minimum inhibitory concentration (MIC)/minimum bactericidal concentration (MBC) and live/dead cell count demonstrated a superior antimicrobial activity of nanoemulsions compared to liposomes against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), and Staphylococcus epidermidis. Nanoemulsion incubation reduced biofilm thickness by 2.4-fold, whereas liposomes showed a 1.6-fold decrease in thickness. SME insertion in the oil-water phase was found to induce bacterial membrane disruption. SME nanosystems were nontoxic to keratinocytes. In vivo topical application of the cationic nanosystems reduced skin infection, MRSA load, and inflammation in mice. The deteriorated skin barrier function evoked by MRSA was recovered by nanoemulsion treatment.

Nanomedicine as a Strategy for Natural Compound Delivery to Prevent and Treat Cancers.

BACKGROUND: Of the >140 anticancer drugs approved since 1940 and available for clinical application, >60% can be traced to a natural product. Of the small molecules among them, 67% are natural in origin. Nanocarriers can be effective anticancer drug delivery systems for preventing and treating cancers. It has been demonstrated that nanoparticles used for drug therapy provide some advantages over conventional formulations, including increased solubility, enhanced storage stability, improved permeability and bioavailability, prolonged half-life, tissue targeting, and minimal side effects. METHODS: In recent years, the concept of using nanoparticles as the carriers of natural products or herbal drugs has attracted increasing attention. This review highlights recent developments using nanomedical approaches for natural product delivery. RESULTS: We systematically introduce the concepts and amelioration mechanisms of the nanomedical techniques for natural product cancer therapy. These modalities are useful in the therapy incorporating a wide variety of natural products for treating brain, lung, breast, and colorectal cancers. The nanosystems for biomedicine can be categorized into three groups: polymeric, lipid, and metallic nanoparticles. All of these have been employed as anticancer carriers for natural products. This review describes various nanocarriers loaded with natural compounds for passive or active targeting of tumors. CONCLUSION: The nanomedicine research data for phytomedicine cancer remedies suggest a way forward for generating advances in chemotherapy.

Non-ablative fractional laser assists cutaneous delivery of small- and macro-molecules with minimal bacterial infection risk.

Use of the ablative laser has been approved to enhance topical drug penetration. Investigation into the usefulness of the non-ablative laser for assisting drug delivery is very limited. In this study, we explored the safety and efficacy of the non-ablative fractional erbium:glass (Er:glass) laser as an enhancement approach to promote drug permeation. Both pig and nude mouse skins were employed as transport barriers. We histologically examined the skin structure after laser exposure. The permeants of 5-aminolevulinic acid (ALA), imiquimod, tretinoin, peptide, dextrans and quantum dots (QD) were used to evaluate in vitro and in vivo skin passage. The fractional laser selectively created an array of photothermal dots deep into the dermis with the preservation of the stratum corneum and epidermis. The barrier function of the skin could be recovered 8-60h post-irradiation depending on the laser spot densities. The application of the laser caused no local infection of Staphylococcus aureus and Pseudomonas aeruginosa. Compared to intact skin, ALA flux was enhanced up to 1200-fold after laser exposure. The penetration enhancement level by the laser was decreased following the increase of permeant lipophilicity. The skin accumulation of tretinoin, an extremely lipophilic drug, showed only a 2-fold elevation by laser irradiation. The laser promoted peptide penetration 10-fold compared to the control skin. Skin delivery of dextrans with a molecular weight (MW) of at least 40kDa could be achieved with the Er:glass laser. QD with a diameter of 20nm penetrated into the skin with the assistance of the non-ablative laser. The confocal microscopic images indicated the perpendicular and lateral diffusions of dextrans and nanoparticles via laser-created microscopic thermal zones. Controlled Er:glass laser irradiation offers a valid enhancement strategy to topically administer the permeants with a wide MW and lipophilicity range.

The codrug approach for facilitating drug delivery and bioactivity.

INTRODUCTION: Codrug or mutual prodrug is a drug design approach to chemically bind two or more drugs to improve therapeutic efficiency or decrease adverse effects. The codrug can be cleaved in the body to generate parent actives. The codrug itself can be inactive, less active, or more active than the parent agents. It has been demonstrated that codrugs possess some benefits over conventional drugs, including enhanced solubility, increased permeation for passing across biomembranes, prolonged half-life for extending the therapeutic period, and reduced toxicity. AREAS COVERED: This review article describes the history, design strategy, and potential applications of codrugs. Codrugs are predominantly used to treat some conditions such as neurodegenerative, cardiovascular, cancerous, infectious, and inflammatory disorders. Many codrugs are developed to increase lipophilicity for better transport into/across biomembranes, especially the skin and cornea. A targeted delivery of codrugs to specific tissues or organs thus can be achieved to promote bioavailability. The chemical and enzymatic hydrolysis, bioactivity, and pharmacokinetics of codrugs are systematically introduced in this review. EXPERT OPINION: Additional profiles pertaining to clinical trials will support further applicability of codrug therapy. Caution should be used in optimizing the benefits of codrugs to ensure a balance between damage or toxicity and the effectiveness of delivery enhancement.

Noninvasive approach for enhancing small interfering RNA delivery percutaneously.

INTRODUCTION: Topically applied small interfering RNA (siRNA) can be an effective treatment for skin disorders. Using noninvasive strategies can be a safe and effective siRNA-permeation-enhancement approach for facilitating skin delivery. It has been demonstrated that noninvasive approaches for enhancing siRNA transport provide some advantages, including enhanced storage stability, targeted delivery, improved permeability and increased bioavailability. AREAS COVERED: This review describes recent developments using noninvasive approaches for siRNA absorption enhancement. This review systematically introduces the concepts and enhancement mechanisms of the techniques, highlighting the potential of these techniques for increasing gene absorption via the skin. These techniques include nanomedicine, penetration enhancers, matrix-based delivery, microneedles, iontophoresis, electroporation and lasers. These modalities are useful for enhancing the permeation of a wide variety of siRNA for treating skin cancers, gene-related diseases, immune-related diseases and cutaneous wounds. EXPERT OPINION: The potential use of the noninvasive approaches affords a new treatment for topical siRNA application with significant efficacy. Further studies using a large group for humans or patients are needed to confirm and clarify the findings in animal studies. Although a safe and nontoxic outcome is claimed, the possible adverse effects and irritation elicited by the noninvasive techniques cannot be ignored.

The roles of the virulence factor IpaB in Shigella spp. in the escape from immune cells and invasion of epithelial cells.

Shigellosis is an acute invasive enteric infection by the Gram negative pathogen Shigella, which causes human diarrhea. Shigella, which are highly epidemic and pathogenic, have become a serious public health problem. The virulence plasmid is a large plasmid essential to the infected host cells. Many virulence factors are encoded in the ipa-mxi-spa region by the virulence plasmid. IpaB is a multifunctional and essential virulence factor in the infection process. In this review article, we introduce the recent studies of the effect of IpaB in Shigella-infected host cells. IpaB is involved in a type III secretion system (T3SS) structure. It also controls the secretion of virulence factors and Shigella adhesion to host cells. In addition, it forms the ion pore, destroys phagosomes, and induces the immune cell's apoptosis or necrosis. Moreover, IpaB can become a potential antigen for Shigella vaccine development.

Cutaneous delivery of natural antioxidants: the enhancement approaches.

Topically applied natural antioxidants can be an effective treatment for inhibiting oxidative damage and photoaging of the skin. Due to the barrier function of the stratum corneum (SC), it is necessary to use an enhancement approach to promote the cutaneous absorption of natural antioxidants. Some factors that should be considered when developing delivery systems for natural antioxidants include increased solubility, enhanced storage stability, improved permeability and bioavailability, skin targeting, and minimal side effects. This review describes the skin delivery systems for natural antioxidant permeation that have been developed during the last decade. The antioxidants introduced include vitamins, polyphenols, and carotenoids. Various types of formulations are employed to improve the skin penetration of the antioxidants, such as hydrogels, cyclodextrin, microemulsions, nanoparticles, liposomes and niosomes. This review focuses on the introduction of natural antioxidants used in skin protection, the mechanisms of antioxidant activity on the skin, and formulation designs for enhancing absorption and efficacy.

The impact of cationic solid lipid nanoparticles on human neutrophil activation and formation of neutrophil extracellular traps (NETs).

Cationic solid lipid nanoparticles (cSLNs) are extensively employed as the nanocarriers for drug/gene targeting to tumors and the brain. Investigation into the possible immune response of cSLNs is still lacking. The aim of this study was to evaluate the impact of cSLNs upon the activation of human polymorphonuclear neutrophil cells (PMNs). The cytotoxicity, pro-inflammatory mediators, Ca(2+) mobilization, mitogen-activated protein kinases (MAPKs), and neutrophil extracellular traps (NETs) as the indicators of PMN stimulation were examined in this work. The cSLNs presented a diameter of 195 nm with a zeta potential of 44 mV. The cSLNs could interact with the cell membrane to produce a direct membrane lysis and the subsequent cytotoxicity according to lactate dehydrogenase (LDH) elevation. The interaction of cSLNs with the membrane also triggered a Ca(2+) influx, followed by the induction of oxidative stress and degranulation. The cationic nanoparticles elevated the levels of superoxide anion and elastase by 24- and 9-fold, respectively. The PMN activation by cSLNs promoted the phosphorylation of p38 and Jun-N-terminal kinases (JNK) but not extracellular signal-regulated kinases (ERK). The imaging of scanning electron microscopy (SEM) and immunofluorescence demonstrated the production of NETs by cSLNs. This phenomenon was not significant for the neutral SLNs (nSLNs), although histones in NETs also increased after treatment of nSLNs. Our results suggest an important role of cSLNs in governing the activation of human neutrophils.

Self-nanoemulsifying drug delivery systems ameliorate the oral delivery of silymarin in rats with Roux-en-Y gastric bypass surgery.

Roux-en-Y gastric bypass (RYGB) is a popular surgery to reduce the body weight of obese patients. Although food intake is restricted by RYGB, drug absorption is also decreased. The purpose of this study was to develop novel self-nanoemulsifying drug delivery systems (SNEDDS) for enhancing the oral delivery of silymarin, which has poor water solubility. The SNEDDS were characterized by size, zeta potential, droplet number, and morphology. A technique of RYGB was performed in Sprague-Dawley rats. SNEDDS were administered at a silymarin dose of 600 mg/kg in normal and RYGB rats for comparison with silymarin aqueous suspension and polyethylene glycol (PEG) 400 solution. Plasma silibinin, the main active ingredient in silymarin, was chosen for estimating the pharmacokinetic parameters. SNEDDS diluted in simulated gastric fluid exhibited a droplet size of 190 nm with a spherical shape. The nanocarriers promoted silibinin availability via oral ingestion in RYGB rats by 2.5-fold and 1.5-fold compared to the suspension and PEG 400 solution, respectively. A significant double-peak concentration of silibinin was detected for RYGB rats receiving SNEDDS. Fluorescence imaging showed a deeper and broader penetration of Nile red, the fluorescence dye, into the gastrointestinal mucosa from SNEDDS than from PEG 400 solution. Histological examination showed that SNEDDS caused more minor inflammation at the gastrointestinal membrane as compared with that caused by PEG 400 solution, indicating a shielding of direct silymarin contact with the mucosa by the nanodroplets. SNEDDS generally showed low-level or negligible irritation in the gastrointestinal tract. Silymarin-loaded SNEDDS were successfully developed to improve the dissolution, permeability, and oral bioavailability of silymarin. To the best of our knowledge, this is the first investigation reporting the usefulness of SNEDDS for improving drug malabsorption elicited by gastric bypass surgery.

Development and validation of stability-indicating high performance liquid chromatography method to analyze gatifloxacin in bulk drug and pharmaceutical preparations.

Quantitative determination of gatifloxacin in tablets, solid lipid nanoparticles (SLNs) and eye-drops using a very simple and rapid chromatographic technique was validated and developed. Formulations were analyzed using a reverse phase SUPELCO® 516 C-18-DB, 50306-U, HPLC column (250 mm × 4.6 mm, 5 µm) and a mobile phase consisting of disodium hydrogen phosphate buffer:acetonitrile (75:25, v/v) and with orthophosphoric acid pH was adjusted to 3.3 The flow rate was 1.0 mL/min and analyte concentrations were measured using a UV-detector at 293 nm. The analyses were performed at room temperature (25 ± 2 °C). Gatifloxacin was separated in all the formulations within 2.767 min. There were linear calibration curves over a concentration range of 4.0-40 µg.mL(-1) and correlation coefficients of 0.9998 with an average recovery above 99.91%. Detection of analyte from different dosage forms at the same Rt indicates the specificity and stability of the developed method.

Fractional thermolysis by bipolar radiofrequency facilitates cutaneous delivery of peptide and siRNA with minor loss of barrier function.

PURPOSE: In this study, we aimed to illustrate the utility of fractional radiofrequency (RF) that generated microchannels in the skin, allowing delivery of peptide and siRNA via the skin. The mechanisms involved in the correlation between macromolecule permeation and skin structure were also elucidated. METHODS: The morphology of the skin was examined by transmission electron microscopy (TEM), higher harmonic generation microscopy (HGM), and physiological factors. In vivo skin distribution of macromolecules was assessed by fluorescence and confocal microscopies. RESULTS: RF thermolysis selectively created an array of micropores deep into the epidermis without significant removal of the stratum corneum (SC). With energy of 30 mJ, a pore depth of 35 µm was achieved. The bipolar RF resulted in a 3-fold increase of transepidermal water loss (TEWL) compared with intact skin. The respective skin accumulation and flux of the peptide with a molecular weight (MW) of 2335 Da was 3- and 23-fold greater for the RF-treated group than for the non-treatment group. RF enhanced skin accumulation of siRNAs with MW of 10 and 15 kDa by 6.2- and 2.6-fold, respectively. Cutaneous penetration of the macromolecules with an MW of at least 40 kDa could be accomplished by RF. Confocal microscopy imaging revealed that RF could effectively deliver the peptide up to at least a 74-µm depth. The penetration depth of siRNA by RF irradiation was about 50 µm. CONCLUSIONS: The novel RF device efficiently delivered macromolecules into the skin while reserving SC layers to support some barrier functions. In this work, for the first time the assistance of fractional RF on peptide and siRNA transport was demonstrated.

Erbium-yttrium-aluminum-garnet laser irradiation ameliorates skin permeation and follicular delivery of antialopecia drugs.

Alopecia usually cannot be cured because of the available drug therapy being unsatisfactory. To improve the efficiency of treatment, erbium-yttrium-aluminum-garnet (Er-YAG) laser treatment was conducted to facilitate skin permeation of antialopecia drugs such as minoxidil (MXD), diphencyprone (DPCP), and peptide. In vitro and in vivo percutaneous absorption experiments were carried out by using nude mouse skin and porcine skin as permeation barriers. Fluorescence and confocal microscopies were used to visualize distribution of permeants within the skin. Laser ablation at a depth of 6 and 10 µm enhanced MXD skin accumulation twofold to ninefold depending on the skin barriers selected. DPCP absorption showed less enhancement by laser irradiation as compared with MXD. An ablation depth of 10 µm could increase the peptide flux from zero to 4.99 and 0.33 µg cm(-2) h(-1) for nude mouse skin and porcine skin, respectively. The laser treatment also promoted drug uptake in the hair follicles, with DPCP demonstrating the greatest enhancement (sixfold compared with the control). The imaging of skin examined by microscopies provided evidence of follicular and intercellular delivery assisted by the Er-YAG laser. Besides the ablative effect of removing the stratum corneum, the laser may interact with sebum to break up the barrier function, increasing the skin delivery of antialopecia drugs. The minimally invasive, well-controlled approach of laser-mediated drug permeation offers a potential way to treat alopecia. This study's findings provide the basis for the first report on laser-assisted delivery of antialopecia drugs.