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1.
Nicole K. Brogden Stan L. Banks Leslie J. Crofford Audra L. Stinchcomb 《Pharmaceutical research》2013,30(8):1947-1955
Purpose
Microneedles applied to the skin create micropores, allowing transdermal drug delivery of skin-impermeable compounds. The first human study with this technique demonstrated delivery of naltrexone (an opioid antagonist) for two to three days. Rapid micropore closure, however, blunts the delivery window. Application of diclofenac (an anti-inflammatory) allows seven days of naltrexone delivery in animals. The purpose of the current work was to demonstrate delivery of naltrexone for seven days following one microneedle treatment in humans.Methods
Human subjects were treated with microneedles, diclofenac (or placebo), and naltrexone. Impedance measurements were used as a surrogate marker to measure micropore formation, and plasma naltrexone concentrations were measured for seven days post-microneedle application.Results
Impedance dropped significantly from baseline to post-microneedle treatment, confirming micropore formation. Naltrexone was detected for seven days in Group 1 (diclofenac + naltrexone, n?=?6), vs. 72 h in Group 2 (placebo + naltrexone, n?=?2). At study completion, a significant difference in impedance was observed between intact and microneedle-treated skin in Group 1 (confirming the presence of micropores).Conclusion
This is the first study demonstrating week-long drug delivery after one microneedle application, which would increase patient compliance and allow delivery of therapies for chronic diseases. 相似文献2.
Purpose
The purpose of this study was to determine if non-specific COX inhibition could extend pore lifetime in hairless guinea pigs following microneedle treatment.Methods
Hairless guinea pigs were treated with microneedle arrays ± daily application of Solaraze® gel (3% diclofenac sodium (non-specific COX inhibitor) and 2.5% hyaluronic acid); transepidermal water loss was utilized to evaluate pore lifetime. To examine the permeation of naltrexone, additional guinea pigs were treated with microneedles ± daily Solaraze® gel followed by application of a 16% transdermal naltrexone patch; pharmacokinetic analysis of plasma naltrexone levels was performed. Histological analysis was employed to visualize morphological changes following microneedle and Solaraze® treatment.Results
Animals treated with microneedles + Solaraze® displayed extended pore lifetime (determined by transepidermal water loss measurements) for up to 7 days. Enhanced naltrexone permeation was also observed for an extended amount of time in animals treated with microneedles + Solaraze®. No morphological changes resulting from microneedle treatment or COX inhibition were noted.Conclusions
Non-specific COX inhibition is an effective means of extending pore lifetime following microneedle treatment in hairless guinea pigs. This may have clinical implications for extending transdermal patch wear time and therefore increasing patient compliance with therapy. 相似文献3.
Purpose
Lidocaine hydrochloride (LidH) was formulated in sodium carboxymethyl cellulose/ gelatine (NaCMC/GEL) hydrogel and a ‘poke and patch’ microneedle delivery method was used to enhance permeation flux of LidH.Methods
The microparticles were formed by electrostatic interactions between NaCMC and GEL macromolecules within a water/oil emulsion in paraffin oil and the covalent crosslinking was by glutaraldehyde. The GEL to NaCMC mass ratio was varied between 1.6 and 2.7. The LidH encapsulation yield was 1.2 to 7% w/w. LidH NaCMC/GEL was assessed for encapsulation efficiency, zeta potential, mean particle size and morphology. Subsequent in vitro skin permeation studies were performed via passive diffusion and microneedle assisted permeation of LidH NaCMC/GEL to determine the maximum permeation rate through full thickness skin.Results
LidH 2.4% w/w NaCMC/GEL 1:1.6 and 1:2.3 respectively, possessed optimum zeta potential. LidH 2.4% w/w NaCMC/GEL 1:2.3 and 1:2.7 demonstrate higher pseudoplastic behaviour. Encapsulation efficiency (14.9–17.2%) was similar for LidH 2.4% w/w NaCMC/GEL 1:1.6–1:2.3. Microneedle assisted permeation flux was optimum for LidH 2.4% w/w NaCMC/GEL 1:2.3 at 6.1 μg/ml/h.Conclusion
LidH 2.4% w/w LidH NaCMC/GEL 1:2.3 crossed the minimum therapeutic drug threshold with microneedle skin permeation in less than 70 min. 相似文献4.
Naresh Modepalli Seongbong Jo Michael A. Repka S. Narasimha Murthy 《Pharmaceutical research》2013,30(3):889-898
Purpose
Iontophoretic mediated transdermal delivery of ferric pyrophosphate (FPP) in combination with microneedle pretreatment was investigated as a potential treatment for iron deficiency anemia (IDA).Methods
In vitro transdermal delivery studies were performed using hairless rat skin and pharmacodynamic studies were performed in hairless anemic rat model. The hematological and biochemical parameters like hemoglobin, hematocrit and % serum transferrin were monitored in rats at healthy, anemic condition and post treatment. Micropores created by the microneedles were visualized in histological skin sections after staining with hemotoxylin and eosin. The recovery of micropores was investigated in vivo by measuring Transepidermal water loss (TEWL) at different time points.Results
The passive, microneedle and iontophoresis mediated delivery did not lead to significant improvement in hematological and biochemical parameters in anemic rats, when used individually. When iontophoresis (0.15 mA/cm2 for 4 hours) was combined with microneedle pretreatment (for 2 min), therapeutically adequate amount of FPP was delivered and there was significant recovery of rats from IDA.Conclusions
Microneedle and iontophoresis mediated delivery of iron via transdermal route could be developed as a potential treatment for IDA. The transdermal controlled delivery of iron could become a potential, safe and effective alternative to parenteral iron therapy. 相似文献5.
Ryan F. Donnelly Rita Majithiya Thakur Raghu Raj Singh Desmond I. J. Morrow Martin J. Garland Yusuf K. Demir Katarzyna Migalska Elizabeth Ryan David Gillen Christopher J. Scott A. David Woolfson 《Pharmaceutical research》2011,28(1):41-57
Purpose
Design and evaluation of a novel laser-based method for micromoulding of microneedle arrays from polymeric materials under ambient conditions. The aim of this study was to optimise polymeric composition and assess the performance of microneedle devices that possess different geometries.Methods
A range of microneedle geometries was engineered into silicone micromoulds, and their physicochemical features were subsequently characterised.Results
Microneedles micromoulded from 20% w/w aqueous blends of the mucoadhesive copolymer Gantrez® AN-139 were surprisingly found to possess superior physical strength than those produced from commonly used pharma polymers. Gantrez® AN-139 microneedles, 600 ??m and 900 ??m in height, penetrated neonatal porcine skin with low application forces (>0.03 N per microneedle). When theophylline was loaded into 600 ??m microneedles, 83% of the incorporated drug was delivered across neonatal porcine skin over 24 h. Optical coherence tomography (OCT) showed that drug-free 600 ??m Gantrez® AN-139 microneedles punctured the stratum corneum barrier of human skin in vivo and extended approximately 460 µm into the skin. However, the entirety of the microneedle lengths was not inserted.Conclusion
In this study, we have shown that a novel laser engineering method can be used in micromoulding of polymeric microneedle arrays. We are currently carrying out an extensive OCT-informed study investigating the influence of microneedle array geometry on skin penetration depth, with a view to enhanced transdermal drug delivery from optimised laser-engineered Gantrez® AN-139 microneedles. 相似文献6.
Jaspreet Singh Kochhar Parthiban Anbalagan Sandeep Balu Shelar Jun Kai Neo Ciprian Iliescu Lifeng Kang 《Pharmaceutical research》2014,31(7):1724-1734
Purpose
To fabricate microneedle arrays directly off a photomask using a simple photolithographical approach and evaluate their potential for delivering collagen.Methods
A simple photolithographical approach was developed by using photomask consisting of embedded micro-lenses that govern microneedle geometry in a mould free process. Microneedle length was controlled by use of simple glass scaffolds as well as addition of backing layer. The fabricated arrays were tested for their mechanical properties by using a force gauge as well as insertion into human skin with trypan blue staining. Microneedle arrays were then evaluated for the delivery of fluorescent collagen, which was evaluated using a confocal laser scanning microscope.Results
Microneedles with sharp tips ranging between 41.5?±?8.4 μm and 71.6?±?13.7 μm as well as of two different lengths of 1336?±?193 μm and 957?±?171 μm were fabricated by using the photomasks. The microneedles were robust and resisted fracture forces up to 25 N. They were also shown to penetrate cadaver human skin samples with ease; especially microneedle arrays with shorter length of 957 μm penetrated up to 72% of needles. The needles were shown to enhance permeation of collagen through cadaver rat skin, as compared to passive diffusion of collagen.Conclusions
A simple and mould free approach of fabricating polymeric microneedle array is proposed. The fabricated microneedle arrays enhance collagen permeation through skin. 相似文献7.
Purpose
To evaluate the feasibility of coating formulated recombinant human erythropoietin alfa (EPO) on a titanium microneedle transdermal delivery system, ZP-EPO, and assess preclinical patch delivery performance.Methods
Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. EPO liquid formulation was coated onto titanium microneedles by dip-coating and drying. Stability of coated EPO was assessed by SEC-HPLC, CZE and potency assay. Preclinical in vivo delivery and pharmacokinetic studies were conducted in rats with EPO-coated microneedle patches and compared to subcutaneous EPO injection.Results
Studies demonstrated successful EPO formulation development and coating on microneedle arrays. ZP-EPO patch was stable at 25°C for at least 3?months with no significant change in % aggregates, isoforms, or potency. Preclinical studies in rats showed the ZP-EPO microneedle patches, coated with 750?IU to 22,000?IU, delivered with high efficiency (75?C90%) with a linear dose response. PK profile was similar to subcutaneous injection of commercial EPO.Conclusions
Results suggest transdermal microneedle patch delivery of EPO is feasible and may offer an efficient, dose-adjustable, patient-friendly alternative to current intravenous or subcutaneous routes of administration. 相似文献8.
Jing Tu Guangsheng Du M. Reza Nejadnik Juha Mönkäre Koen van der Maaden Paul H. H. Bomans Nico A. J. M. Sommerdijk Bram Slütter Wim Jiskoot Joke A. Bouwstra Alexander Kros 《Pharmaceutical research》2017,34(8):1693-1706
Purpose
To develop a new intradermal antigen delivery system by coating microneedle arrays with lipid bilayer-coated, antigen-loaded mesoporous silica nanoparticles (LB-MSN-OVA).Methods
Synthesis of MSNs with 10-nm pores was performed and the nanoparticles were loaded with the model antigen ovalbumin (OVA), and coated with a lipid bilayer (LB-MSN-OVA). The uptake of LB-MSN-OVA by bone marrow-derived dendritic cells (BDMCs) was studied by flow cytometry. The designed LB-MSN-OVA were coated onto pH-sensitive pyridine-modified microneedle arrays and the delivery of LB-MSN-OVA into ex vivo human skin was studied.Results
The synthesized MSNs demonstrated efficient loading of OVA with a maximum loading capacity of about 34% and the lipid bilayer enhanced the colloidal stability of the MSNs. Uptake of OVA loaded in LB-MSN-OVA by BMDCs was higher than that of free OVA, suggesting effective targeting of LB-MSN-OVA to antigen-presenting cells. Microneedles were readily coated with LB-MSN-OVA at pH 5.8, yielding 1.5 μg of encapsulated OVA per microneedle array. Finally, as a result of the pyridine modification, LB-MSN-OVA were effectively released from the microneedles upon piercing the skin.Conclusion
Microneedle arrays coated with LB-MSN-OVA were successfully developed and shown to be suitable for intradermal delivery of the encapsulated protein antigen.9.
Bekir Bediz Emrullah Korkmaz Rakesh Khilwani Cara Donahue Geza Erdos Louis D. Falo Jr O. Burak Ozdoganlar 《Pharmaceutical research》2014,31(1):117-135
Purpose
Design and evaluate a new micro-machining based approach for fabricating dissolvable microneedle arrays (MNAs) with diverse geometries and from different materials for dry delivery to skin microenvironments. The aims are to describe the new fabrication method, to evaluate geometric and material capability as well as reproducibility of the method, and to demonstrate the effectiveness of fabricated MNAs in delivering bioactive molecules.Methods
Precise master molds were created using micromilling. Micromolding was used to create elastomer production molds from master molds. The dissolvable MNAs were then fabricated using the spin-casting method. Fabricated MNAs with different geometries were evaluated for reproducibility. MNAs from different materials were fabricated to show material capability. MNAs with embedded bioactive components were tested for functionality on human and mice skin.Results
MNAs with different geometries and from carboxymethyl cellulose, polyvinyl pyrrolidone and maltodextrin were created reproducibly using our method. MNAs successfully pierce the skin, precisely deliver their bioactive cargo to skin and induce specific immunity in mice.Conclusions
We demonstrated that the new fabrication approach enables creating dissolvable MNAs with diverse geometries and from different materials reproducibly. We also demonstrated the application of MNAs for precise and specific delivery of biomolecules to skin microenvironments in vitro and in vivo. 相似文献10.
Scott A. Burton Chin-Yee Ng Ryan Simmers Craig Moeckly David Brandwein Tom Gilbert Nathan Johnson Ken Brown Tesha Alston Gayatri Prochnow Kris Siebenaler Kris Hansen 《Pharmaceutical research》2011,28(1):31-40
Purpose
The purpose of this work is to demonstrate rapid intradermal delivery of up to 1.5 mL of formulation using a hollow microneedle delivery device designed for self-application.Methods
3M??s hollow Microstructured Transdermal System (hMTS) was applied to domestic swine to demonstrate delivery of a variety of formulations including small molecule salts and proteins. Blood samples were collected after delivery and analyzed via HPLC or ELISA to provide a PK profile for the delivered drug. Site evaluations were conducted post delivery to determine skin tolerability.Results
Up to 1.5 mL of formulation was infused into swine at a max rate of approximately 0.25 mL/min. A red blotch, the size of the hMTS array, was observed immediately after patch removal, but had faded so as to be almost indistinguishable 10 min post-patch removal. One-mL deliveries of commercial formulations of naloxone hydrochloride and human growth hormone and a formulation of equine anti-tetanus toxin were completed in swine. With few notable differences, the resulting PK profiles were similar to those achieved following subcutaneous injection of these formulations.Conclusions
3M??s hMTS can provide rapid, intradermal delivery of 300?C1,500 µL of liquid formulations of small molecules salts and proteins, compounds not typically compatible with passive transdermal delivery. 相似文献11.
Purpose
Topical beta-blockers are efficacious for treating infantile hemangiomas, but no formulations have been specifically optimized for skin delivery. Our objective was to quantify skin concentrations and drug permeation of propranolol (a nonselective beta-blocker) after application of microemulsions to intact and microneedle pretreated skin.Methods
Four propranolol-loaded microemulsions were characterized for droplet size, surface charge, conductivity, pH, drug solubility, and drug release. Skin concentrations and drug permeation through skin were quantified using LC-MS. Skin-to-receiver ratios were used to compare the microemulsion formulations to a drug-in-PBS solution.Results
Propranolol solubility was significantly greater in microemulsions vs PBS. Cumulative drug release from the microemulsions over 24 h ranged from 13 to 26%. Skin concentrations and drug permeation through intact skin was significantly higher from PBS; however, the skin-to-receiver ratios were significantly higher for water-rich microemulsions compared to PBS or surfactant-rich microemulsions. Microneedle pretreatment significantly increased skin concentrations for all formulations. Skin-to-receiver ratios significantly increased after microneedle pretreatment for surfactant-rich microemulsions.Conclusions
Microemulsion formulation can be altered to elicit different drug delivery profiles through MN-treated skin. This could be advantageous for maximizing local skin drug concentrations and improving dosing schedules for infantile hemangioma treatment.12.
Chenchen Guo Rajeshree H. Khengar Mingjing Sun Zheng Wang Aiping Fan Yanjun Zhao 《Pharmaceutical research》2014,31(11):3051-3059
Purpose
The acne skin is characteristic of a relatively lower pH microenvironment compared to the healthy skin. The aim of this work was to utilize such pH discrepancy as a site-specific trigger for on-demand topical adapalene delivery.Methods
The anti-acne agent, adapalene, was encapsulated in acid-responsive polymer (Eudragit® EPO) nanocarriers via nanoprecipitation. The nanocarriers were characterized in terms of particle size, surface morphology, drug-carrier interaction, drug release and permeation.Results
Adapalene experienced a rapid release at pH 4.0 in contrast to that at pH 5.0 and 6.0. The permeation study using silicone membrane revealed a significant higher drug flux from the nanocarrier (6.5?±?0.6 μg.cm?2.h?1) in comparison to that (3.9?±?0.4 μg.cm?2.h?1) in the control vehicle (Transcutol®). The in vitro pig skin tape stripping study showed that at 24 h post dose-application the nanocarrier delivered the same amount of drug to the stratum corneum as the positive control vehicle did.Conclusions
The acid-responsive nanocarriers hold promise for efficient adapalene delivery and thus improved acne therapy. FigurepH liable nanocarriers enhance the adapalene delivery to acne skin. 相似文献
13.
Purpose
In principle, maximum transepidermal fluxes of solutes should be similar for different vehicles, except when the solute or vehicle modifies the skin. Here we estimated maximum flux, stratum corneum solubility, diffusivity and permeability coefficient for a range of similarly sized phenolic compounds with varying lipophilicity from polar and lipophilic vehicles.Methods
Maximum flux and other skin transport parameters through human epidermis were obtained from lipophilic vehicles (mineral oil (MO) and isopropyl myristate (IPM)) and compared with values from water and propylene glycol (PG)-water solutions. Solvent uptake and changes in stratum corneum infrared spectroscopy and multiphoton microscopy imaging were also investigated.Results
Maximum fluxes for MO and water were similar but IPM has a higher value for more polar phenols due to a higher diffusivity and PG-water had a higher flux due to higher solubility in the stratum corneum. Whereas maximum flux for various phenols was directly related to solubility in the stratum corneum independent of vehicle, increasing phenol lipophilicity increased and decreased permeability coefficient for aqueous solvents and lipophilic solvents, respectively.Conclusion
The maximum fluxes for phenols with a similar molecular size and varying lipophilicity were comparable between water and MO vehicles but higher for IPM and PG-water mixtures. 相似文献14.
Leonard Y. Chu Ling Ye Ke Dong Richard W. Compans Chinglai Yang Mark R. Prausnitz 《Pharmaceutical research》2016,33(4):868-878
Purpose
This study tested the hypothesis that encapsulation of influenza vaccine in microneedle patches increases vaccine stability during storage at elevated temperature.Methods
Whole inactivated influenza virus vaccine (A/Puerto Rico/8/34) was formulated into dissolving microneedle patches and vaccine stability was evaluated by in vitro and in vivo assays of antigenicity and immunogenicity after storage for up to 3 months at 4, 25, 37 and 45°C.Results
While liquid vaccine completely lost potency as determined by hemagglutination (HA) activity within 1–2 weeks outside of refrigeration, vaccine in microneedle patches lost 40–50% HA activity during or shortly after fabrication, but then had no significant additional loss of activity over 3 months of storage, independent of temperature. This level of stability required reduced humidity by packaging with desiccant, but was not affected by presence of oxygen. This finding was consistent with additional stability assays, including antigenicity of the vaccine measured by ELISA, virus particle morphological structure captured by transmission electron microscopy and protective immune responses by immunization of mice in vivo.Conclusions
These data show that inactivated influenza vaccine encapsulated in dissolving microneedle patches has enhanced stability during extended storage at elevated temperatures.15.
Vávrová K Kovaříková P Skolová B Líbalová M Roh J Cáp R Holý A Hrabálek A 《Pharmaceutical research》2011,28(12):3105-3115
Purpose
Acyclic nucleoside phosphonates possess unique antiviral and antineoplastic activities; however, their polar phosphonate moiety is associated with low ability to cross biological membranes. We explored the potential of transdermal and topical delivery of 2,6-diaminopurine derivative cPr-PMEDAP.Methods
In vitro diffusion of cPr-PMEDAP was investigated using formulations at different pH and concentration and with permeation enhancer through porcine and human skin.Results
Ability of 0.1?C5% cPr-PMEDAP to cross human skin barrier was very low with flux values ~40 ng/cm2/h, the majority of compound found in the stratum corneum. The highest permeation rates were found at pH 6; increased donor concentration had no influence. The permeation enhancer dodecyl 6-dimethylaminohexanoate (DDAK, 1%) increased flux of cPr-PMEDAP (up to 61 times) and its concentration in nucleated epidermis (up to ~0.5 mg of cPr-PMEDAP/g of the tissue). No deamination of cPr-PMEDAP into PMEG occurred during permeation studies, but N-dealkylation into PMEDAP mediated by skin microflora was observed.Conclusions
Transdermal or topical application of cPr-PMEDAP enabled by the permeation enhancer DDAK may provide an attractive alternative route of administration of this potent antitumor and antiviral compound. 相似文献16.
Purpose
Electrochemical impedance spectroscopy is a convenient method that has been used to characterize skin barrier function, which affects drug delivery into and through the skin. The objective of this study was to relate changes in skin barrier function arising from mechanical damage to changes in the impedance spectra. These observations are compared in a companion paper to changes in chemically damaged skin.Methods
Electrical impedance and the permeation of a non-polar compound were measured before and after human cadaver skin was damaged by needle puncture.Results
The impedance responses of all skin samples were consistent with an equivalent circuit model with a resistor and constant phase element (CPE) in parallel. Pinhole-damaged skin exhibited a lower resistance pathway acting in parallel with the skin resistance without changing the CPE behavior. The characteristic frequency of the impedance scans determined after needle puncture increased by an amount that could be predicted. The flux of 4-cyanophenol increased by a small but significant amount that did not correlate with the hole resistance calculated under the assumption that the resistance of the surrounding skin did not change.Conclusions
Skin impedance measurements are sensitive to irreversible damage caused by exposure to puncture with a needle. 相似文献17.
Himanshu Kathuria Hairui Li Jing Pan Seng Han Lim Jaspreet Singh Kochhar Chunyong Wu Lifeng Kang 《Pharmaceutical research》2016,33(11):2653-2667
Purpose
Current topical treatments using lidocaine (LD) for analgesia have limited applications due to their delayed analgesic actions, resulted from slow drug permeation through skin. The aim of this study is to fabricate a large size microneedle (MN) array patch containing LD, with fast onset of action, for the treatment of acute and chronic pain.Methods
The MN patch was developed through photolithography and tested for its mechanical characteristics. In vitro and in vivo skin permeation, plasma pharmacokinetics, histology and skin irritation testing have also been performed for the MN patches.Results
The MN have a mechanical strength of 10–30 N and more than 90% of the microneedles on the patch penetrated skin. It was shown that LD permeated through skin within 5 min of patch application. Subsequently, the in vivo skin permeation study using a porcine model showed that LD administrated by the MN patch was able to achieve the therapeutic level locally within 10 min and sustained for 8 h. It shows most of the drug diffuses perpendicularly against skin, with little lateral diffusion. After skin permeation LD remains within skin and unquantifiable amount of LD was found in the plasma of the pigs. Minor skin irritations were observed after 6 h of microneedle contact. However, the skin irritations resolved within 1 day following the removal of MN patch.Conclusion
The large size MN patches showed fast onset and sustained delivery of LD through skin, potentially useful to increase the application scope of topical LD for pain management.18.
Ryan F. Donnelly Kurtis Moffatt Ahlam Zaid Alkilani Eva M. Vicente-Pérez Johanne Barry Maelíosa T. C. McCrudden A. David Woolfson 《Pharmaceutical research》2014,31(8):1989-1999
Purpose
To investigate, for the first time, the influence of pharmacist intervention and the use of a patient information leaflet on self-application of hydrogel-forming microneedle arrays by human volunteers without the aid of an applicator device.Methods
A patient information leaflet was drafted and pharmacist counselling strategy devised. Twenty human volunteers applied 11?×?11 arrays of 400 μm hydrogel-forming microneedle arrays to their own skin following the instructions provided. Skin barrier function disruption was assessed using transepidermal water loss measurements and optical coherence tomography and results compared to those obtained when more experienced researchers applied the microneedles to the volunteers or themselves.Results
Volunteer self-application of the 400 μm microneedle design resulted in an approximately 30% increase in skin transepidermal water loss, which was not significantly different from that seen with self-application by the more experienced researchers or application to the volunteers. Use of optical coherence tomography showed that self-application of microneedles of the same density (400 μm, 600 μm and 900 μm) led to percentage penetration depths of approximately 75%, 70% and 60%, respectively, though the diameter of the micropores created remained quite constant at approximately 200 μm. Transepidermal water loss progressively increased with increasing height of the applied microneedles and this data, like that for penetration depth, was consistent, regardless of applicant.Conclusion
We have shown that hydrogel-forming microneedle arrays can be successfully and reproducibly applied by human volunteers given appropriate instruction. If these outcomes were able to be extrapolated to the general patient population, then use of bespoke MN applicator devices may not be necessary, thus possibly enhancing patient compliance. 相似文献19.
Woan-Ruoh Lee Shing-Chuan Shen Ibrahim A. Aljuffali Yi-Ching Li Jia-You Fang 《Pharmaceutical research》2014,31(2):382-393
Purpose
This study aimed to assess impact of different vehicles for laser-assisted skin drug delivery. We also tried to uncover the mechanisms by which different vehicles affect laser-aided skin permeation.Methods
Full-surface ablative (conventional) and fractional lasers were used to irradiate nude mouse skin. Imiquimod and 5-aminolevulinic acid (ALA) were used as lipophilic and hydrophilic permeants. Vehicles employed included water with 40% polyethylene glycol 400 (PEG 400), propylene glycol (PG), and ethanol. Lipid nanoparticles were also utilized as carriers.Results
In vitro permeation profiles showed improvement in imiquimod flux with conventional laser (2.5 J/cm2) producing a 12-, 9-, and 5-fold increase when loading imiquimod in 40% PEG400, PG, and ethanol, respectively, as compared with intact skin. Nanoparticulate delivery by laser produced a 6-fold enhancement in permeation. Fractional laser produced less enhancement of imiquimod delivery than conventional laser. Laser exposure increased follicular imiquimod accumulation from 0.80 to 5.81 μg/cm2. ALA permeation from aqueous buffer, PEG 400, and PG with conventional laser treatment was 641-, 445-, and 104-fold superior to passive control. In vivo skin deposition of topically applied ALA examined by confocal microscopy indicated the same trend as the in vitro experiment, with aqueous buffer showing the greatest proporphyllin IX signaling. Diffusion of cosolvent molecules into ablated skin and drug partitioning from vehicle to skin are two predominant factors controlling laser-assisted delivery. In contrast to conventional laser, lateral drug diffusion was anticipated for fractional laser.Conclusions
Our results suggest that different drug delivery vehicles substantially influence drug penetration enhanced by lasers. 相似文献20.
Woan-Ruoh Lee Shing-Chuan Shen Saleh A. Al-Suwayeh Hung-Hsu Yang Yi-Ching Li Jia-You Fang 《Pharmaceutical research》2013,30(3):792-802