Optimization and Characterization of Aqueous Micellar Formulations for Ocular Delivery of an Antifungal Drug, Posaconazole

2020 ◽  
Vol 26 (14) ◽  
pp. 1543-1555 ◽  
Author(s):  
Meltem E. Durgun ◽  
Emine Kahraman ◽  
Sevgi Güngör ◽  
Yıldız Özsoy
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Size Distribution ◽  
Encapsulation Efficiency ◽  
Fungal Infections ◽  
In Vitro Release ◽  
Pluronic F127 ◽  
Glycol Succinate ◽  
Vitro Release

Background: Topical therapy is preferred for the management of ocular fungal infections due to its superiorities which include overcoming potential systemic side effects risk of drugs, and targeting of drugs to the site of disease. However, the optimization of effective ocular formulations has always been a major challenge due to restrictions of ocular barriers and physiological conditions. Posaconazole, an antifungal and highly lipophilic agent with broad-spectrum, has been used topically as off-label in the treatment of ocular fungal infections due to its highly lipophilic character. Micellar carriers have the potential to improve the solubility of lipophilic drugs and, overcome ocular barriers. Objective: In the current study, it was aimed optimization of posaconazole loaded micellar formulations to improve aqueous solubility of posaconazole and to characterize the formulations and to investigate the physical stability of these formulations at room temperature (25°C, 60% RH), and accelerated stability (40°C, 75% RH) conditions. Method: Micelles were prepared using a thin-film hydration method. Pre-formulation studies were firstly performed to optimize polymer/surfactant type and to determine their concentration in the formulations. Then, particle size, size distribution, and zeta potential of the micellar formulations were measured by ZetaSizer Nano-ZS. The drug encapsulation efficiency of the micelles was quantified by HPLC. The morphology of the micelles was depicted by AFM. The stability of optimized micelles was evaluated in terms of particle size, size distribution, zeta potential, drug amount and pH for 180 days. In vitro release studies were performed using Franz diffusion cells. Results: Pre-formulation studies indicated that single D-ɑ-tocopheryl polyethylene glycol succinate (TPGS), a combination of it and Pluronic F127/Pluronic F68 are capable of formation of posaconazole loaded micelles at specific concentrations. Optimized micelles with high encapsulation efficiency were less than 20 nm, approximately neutral, stable, and in aspherical shape. Additionally, in vitro release data showed that the release of posaconazole from the micelles was higher than that of suspension. Conclusion: The results revealed that the optimized micellar formulation of posaconazole offers a potential approach for topical ocular administration.

scholarly journals pH-Responsive Liposomes of Dioleoyl Phosphatidylethanolamine and Cholesteryl Hemisuccinate for the Enhanced Anticancer Efficacy of Cisplatin

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 129
Author(s):  
Hassan Shah ◽  
Asadullah Madni ◽  
Muhammad Muzamil Khan ◽  
Fiaz-ud-Din Ahmad ◽  
Nasrullah Jan ◽  
...  
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Release Rate ◽  
In Vitro Release ◽  
Chemotherapeutic Agents ◽  
Ph Responsive ◽  
Scanning Calorimetry ◽  
Cholesteryl Hemisuccinate ◽  
Vitro Release

The current study aimed to develop pH-responsive cisplatin-loaded liposomes (CDDP@PLs) via the thin film hydration method. Formulations with varied ratios of dioleoyl phosphatidylethanolamine (DOPE) to cholesteryl hemisuccinate (CHEMS) were investigated to obtain the optimal particle size, zeta potential, entrapment efficiency, in vitro release profile, and stability. The particle size of the CDDP@PLs was in the range of 153.2 ± 3.08–206.4 ± 2.26 nm, zeta potential was −17.8 ± 1.26 to −24.6 ± 1.72, and PDI displayed an acceptable size distribution. Transmission electron microscopy revealed a spherical shape with ~200 nm size. Fourier transform infrared spectroscopic analysis showed the physicochemical stability of CDDP@PLs, and differential scanning calorimetry analysis showed the loss of the crystalline nature of cisplatin in liposomes. In vitro release study of CDDP@PLs at pH 7.4 depicted the lower release rate of cisplatin (less than 40%), and at a pH of 6.5, an almost 65% release rate was achieved compared to the release rate at pH 5.5 (more than 80%) showing the tumor-specific drug release. The cytotoxicity study showed the improved cytotoxicity of CDDP@PLs compared to cisplatin solution in MDA-MB-231 and SK-OV-3 cell lines, and fluorescence microscopy also showed enhanced cellular internalization. The acute toxicity study showed the safety and biocompatibility of the developed carrier system for the potential delivery of chemotherapeutic agents. These studies suggest that CDDP@PLs could be utilized as an efficient delivery system for the enhancement of therapeutic efficacy and to minimize the side effects of chemotherapy by releasing cisplatin at the tumor site.

scholarly journals Enhanced Lymphatic Delivery of Methotrexate Using W/O/W Nanoemulsion: In Vitro Characterization and Pharmacokinetic Study

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 978 ◽  
Author(s):  
Ji-Hun Jang ◽  
Seung-Hyun Jeong ◽  
Yong-Bok Lee
Keyword(s):  
Plasma Concentration ◽  
Zeta Potential ◽  
Intravenous Administration ◽  
Half Life ◽  
Encapsulation Efficiency ◽  
In Vitro Release ◽  
Lymphatic Delivery ◽  
Vitro Release ◽  
Lymphatic Targeting

Methotrexate, which is widely used in the treatment of cancer and immune-related diseases, has limitations in use because of its low bioavailability, short half-life, and tissue toxicity. Thus, in this study, a nano-sized water-in-oil-in-water (W/O/W) double emulsion containing methotrexate was prepared to enhance its lymphatic delivery and bioavailability. Based on the results from solubility testing and a pseudo-ternary diagram study, olive oil as the oil, Labrasol as a surfactant, and ethanol as a co-surfactant, were selected as the optimal components for the nanoemulsion. The prepared nanoemulsion was evaluated for size, zeta potential, encapsulation efficiency, pH, morphology, and in vitro release profiles. Furthermore, pharmacokinetics and lymphatic targeting efficiency were assessed after oral and intravenous administration of methotrexate-loaded nanoemulsion to rats. Mean droplet size, zeta potential, encapsulation efficiency, and pH of formulated nanoemulsion were 173.77 ± 5.76 nm, −35.63 ± 0.78 mV, 90.37 ± 0.96%, and 4.07 ± 0.03, respectively. In vitro release profile of the formulation indicated a higher dissolution and faster rate of methotrexate than that of free drug. The prepared nanoemulsion showed significant increases in maximum plasma concentration, area under the plasma concentration-time curve, half-life, oral bioavailability, and lymphatic targeting efficiency in both oral and intravenous administration. Therefore, our research proposes a methotrexate-loaded nanoemulsion as a good candidate for enhancing targeted lymphatic delivery of methotrexate.

scholarly journals FORMULATION OF POLYMERIC NANOSUSPENSION CONTAINING PRAMIPEXOLE DIHYDROCHLORIDE AND HESPERIDIN FOR IMPROVED TREATMENT OF PARKINSON’S DISEASES

2018 ◽  
Vol 11 ◽  
Author(s):  
Somasundaram I
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Zeta Potential ◽  
In Vitro Release ◽  
Entrapment Efficiency ◽  
Burst Release ◽  
Drug Content ◽  
Pramipexole Dihydrochloride ◽  
Vitro Release

Aims and Objectives: The present study is to formulate the nanosuspension containing a hydrophilic drug pramipexole dihydrochloride and hesperidin and to increase the drug entrapment efficiency.Methods: Hesperidin and pramipexole dihydrochloride loaded in chitosan nanosuspension is prepared by ionic gelation method using chitosan and tripolyphosphate. There was no incompatibility observed between the drug and polymer through Fourier transform infrared and differential scanning calorimetric. Various other parameters such as particle size, zeta potential, scanning electron microscope, drug content, drug entrapment efficiency, and in vitro release have been utilized for the characterization of nanoparticles.Results and Discussion: The average size of particle is 188 nm; zeta potential is 46.7 mV; drug content of 0.364±0.25 mg/ml; entrapment efficiency of 72.8% is obtained with HPN3 formulation. The PHC1 shows the highest drug release followed by PHC2 due to low concentration of polymer and PHC4 and PHC5 show less drug release due to high concentration of polymer. The in vitro release of PHC3 is 85.2%, initial the burst release is shown which is approximately 60% in 8 h; then, slow release later on drastic reduction in release rate is shown in 24 h. The in vivo study histopathological report confers the effective protective against rotenone induces Parkinson’s.Conclusion: PHC3 was chosen as the best formulation due to its reduced particle size and controlled release at optimum polymer concentration which may be used to treat Parkinson’s disease effectively..

scholarly journals Application of Molecularly Structured Ben Oil in Gentamicin Entrapped Lipospheres

2019 ◽  
pp. 262-270 ◽  
Author(s):  
Salome A. Chime ◽  
Ikechukwu V. Onyishi ◽  
Ifeoma O. Eze
Keyword(s):  
Particle Size ◽  
Encapsulation Efficiency ◽  
Moringa Oleifera ◽  
Extended Release ◽  
In Vitro Release ◽  
Antimicrobial Studies ◽  
Microbial Inhibition ◽  
Vitro Release ◽  
Moringa Oleifera Seed

Objective: To formulate extended release gentamicin-entrapped lipospheres using natural lipids from Irvingia wombolu (IWF) and Moringa oleifera seed (MO) popularly known as Ben oil. Methods: Different lipid combinations including IWF and Phospholipon 90H (P90H) and IWF and MO were employed in the formulation of lipospheres. The formulations were analysed for particle size, encapsulation efficiency (EE), pH stability and antimicrobial studies amongst other tests. Also the in vitro release properties were studied in Phosphate buffer pH 7.2. Results: High EE of up to 90 % were obtained for the various LM combinations. The pH was stable over 30 days and the formulations showed about 93 % release of gentamicin at 12 h. Lipospheres formulated with MO matrices showed synergism in the microbial inhibition than other formulations. Conclusion: Natural lipids from Irvingia wombolu and Moringa oleifera seed could be used in formulating oral extended release gentamicin lipospheres.

ROSUVASTATIN CALCIUM LOADED CHITOSAN NANOPARTICLES: PREPARATION EVALUATION AND IN VITRO RELEASE STUDIES

2020 ◽  
pp. 95-102
Author(s):  
SUVARNA G. BHOKARE ◽  
RAJENDRA P. MARATHE
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Sustained Release ◽  
Sodium Tripolyphosphate ◽  
Chitosan Nanoparticles ◽  
In Vitro Release ◽  
Particle Diameter ◽  
Vitro Release ◽  
Rosuvastatin Calcium

Objective: The objective of the present study was to develop sustained release biodegradable polymeric nanoparticles of rosuvastatin calcium. Methods: Nanoparticles were prepared by modified ionotropic gelation method using 3² full factorial designs. From the preliminary trials, the constraints for independent variables X1 (concentration. of chitosan) and X2 (concentration. of sodium tripolyphosphate) have been fixed. Factors included concentration of chitosan and sodium tripolyphosphate, have been examined to investigate effect on particle size, encapsulation efficiency, zeta potential, % release, scanning electron microscopy, Fourier transfer infrared study and X-ray diffraction and release study of rosuvastatin calcium nanoparticles. 0 Results: The prepared nanoparticles were white, free-flowing and spherical in shape. The infrared spectra showed stable character of rosuvastatin calcium in the drug-loaded nanoparticles and revealed the absence of drug polymer interactions. The chitosan nanoparticles have a particle diameter ranging approximately 114.5±3.61 to 724±.2.51 nm and a zeta potential-13.12 to-52.63 mV. The in vitro release behavior from all the drug loaded batches were found to follow first order and provided sustained release over a period of 10 h. The Zeta potential of all the batches were in the range of-13.12 to-52.63 mv. The release profiles of all batches were very well fitted by Korsmeyer Peppas model. Conclusion: The best-fit release kinetics was achieved with Korsmeyer peppas model. The release of rosuvastatin calcium was influenced by the drug to polymer ratio and particle size. These results indicate that rosuvastatin calcium nanoparticles could be effective in sustaining drug release for a prolonged period.

scholarly journals INVESTIGATION OF EFFECT OF PHOSPHOLIPIDS ON PHYSICAL AND FUNCTIONAL CHARACTERIZATION OF PACLITAXEL LIPOSOMES

2017 ◽  
Vol 9 (12) ◽  
pp. 141
Author(s):  
Amol A. Tatode ◽  
Arun T. Patil ◽  
Milind J. Umekar ◽  
Darshan R. Telange
Keyword(s):  
Particle Size ◽  
Particle Size Distribution ◽  
Size Distribution ◽  
Functional Characterization ◽  
In Vitro Release ◽  
Entrapment Efficiency ◽  
Stoichiometric Ratio ◽  
Hemolytic Toxicity ◽  
Vitro Release

Objective: Aim of the present investigation was to determine the effect of various synthetic grades of phospholipids on paclitaxel liposomes (PTL).Methods: The PTL formulations using various grades of phospholipids were prepared by film hydration method. The prepared PTL formulations were physicochemically characterized by entrapment efficiency (EE, %w/w), vesicular size and particle size distribution. These formulations were also characterized for function parameters such as in vitro release and hemolytic toxicity assay.Results: The synthetic grades of phospholipids significantly influenced PTL formulations. The stoichiometric ratio (1:1) between CH and various synthetic phospholipids was found to be optimized one, from rest of the ratios. The characterization confirmed the formation of PTL. The EE was observed to be high (86.67%) as increasing the ratios between CH and phospholipids but then declined suddenly as further increasing the ratio. The best liposomal formulations showed that the spherical shape was found to be within size ranging from<10 µm, with a higher rate and extent of the release, ~86.22% of paclitaxel from PTL formulation. The results of the hemolytic toxicity study demonstrated that PTL formulations with a ratio (1:1) exhibited a significantly lower hemolytic toxicity (2.70%), compared to all formulations.Conclusion: The result revealed the excellent effect of phospholipids on paclitaxel liposomes. The paclitaxel liposomes prepared with CH: PL90G ratio (1:1) was found to be optimized one. The entrapment efficiency, particle size distribution, in vitro release and hemolytic activity with this ratio shown to be excellent as compared to other ratios.

scholarly journals Glycyrrhetinic Acid Liposomes and Hyalurosomes on Spanish Broom, Flax, and Hemp Dressings to Heal Skin Wounds

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2558 ◽  
Author(s):  
Angela Abruzzo ◽  
Concettina Cappadone ◽  
Giovanna Farruggia ◽  
Barbara Luppi ◽  
Federica Bigucci ◽  
...  
Keyword(s):  
Size Distribution ◽  
Encapsulation Efficiency ◽  
Healing Process ◽  
In Vitro Release ◽  
Glycyrrhetinic Acid ◽  
Skin Wounds ◽  
Ζ Potential ◽  
Biological Studies ◽  
Vitro Release

The focus of this work was to prepare Spanish Broom, flax, and hemp dressings impregnated with glycyrrhetinic acid (GA) liposomes or hyalurosomes to promote the healing process and protect the skin wounds. Vesicles were prepared by the film hydration method and characterized in terms of size, particle size distribution, ζ potential, encapsulation efficiency, in vitro release, and biocompatibility on 3T3 fibroblasts. Loaded liposomes and hyalurosomes showed nanometric size (355 ± 19 nm and 424 ± 32 nm, respectively), good size distribution (lower than 0.3), and appropriate encapsulation efficiency (58.62 ± 3.25% and 59.22 ± 8.18%, respectively). Hyalurosomes showed good stability during the storage period, which can be correlated to the negative ζ potential, and allowed a fast and complete release of GA. Preliminary biological studies revealed that both kinds of loaded vesicles were not cytotoxic and that hyalurosomes could exert a slight stimulating effect on fibroblast proliferation. Finally, in vitro release studies from the different dressings impregnated with the loaded vesicles demonstrated that a high amount of GA could be reached at the wound site after 60 min from application. In conclusion, the results suggested that the developed dressings, especially those impregnated with hyalurosomes, can be efficiently used to promote the healing process.

scholarly journals Development of Intranasal Levothyroxine Powder Delivery for Hypothyroidism

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A828-A829
Author(s):  
Syed Ali Imran ◽  
Obinna Esomchukwu ◽  
Remigius Agu
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Surface Morphology ◽  
Freeze Drying ◽  
Significant Proportion ◽  
In Vitro Release ◽  
X Ray ◽  
Freeze Dried ◽  
Vitro Release

Abstract Background: Hypothyroidism affects 3-5% of the general population with oral levothyroxine (LT4) being the predominant replacement therapy. However, significant proportion of hypothyroid patients are unable to absorb oral replacement leading to therapeutic failure and may require injectable thyroxine. Objectives: To develop non-invasive, less costly, and patient-friendly LT4 nasal delivery alternative using mucoadhesive polymers: chitosan and hydroxypropylmethylcellulose (HPMC). Methods: Six nasal LT4 formulations were developed with either chitosan or hydroxypropyl methylcellulose as mucoadhesive. The formulations were prepared through freeze-drying by varying the drug to polymer ratio (1:1, 1:3, and 1:5). The percentage drug yield was calculated by analyzing the weight of the formulation pre- and post-freeze drying. HPLC analysis was conducted to determine the amount of LT4 loaded in each formulation. Furthermore, the surface morphology, particle size, zeta potential, differential scanning calorimetry, X-ray diffraction as well as the in vitro release were assessed to determine the physicochemical properties and release characteristics of the formulations, respectively. Results: Both percentage drug loading and yield were &gt; 70% for all the formulations. The freeze-dried formulations displayed a compact needle-like surface morphology. LT4-chitosan formulations, 1:1, 1:3, and 1:5 had mean particle size of 2.45 ± 0.88 µm, 2.76 ± 1.38 µm, and 1.59 ± 0.27 µm, respectively. Mean particle sizes for 1:1, 1:3, and 1:5 LT4-HPMC formulations were 0.56 ± 0.02 µm, 0.22 ± 0.06 µm, and 0.46 ± 0.04 µm. Zeta potential for LT4-chitosan formulation 1:1, 1:3, and 1:5 were -18.7 ± 1.00 mV, -16.2 ± 0.79 mV, and -19.17 ± 1.01 mV, respectively. LT4-HPMC 1:1, 1:3, and 1:5 formulations had zeta charges of -11.66 ± 3.16 mV, -6.06 ± 3.92 mV, and -9.53 ± 1.68 mV, respectively. Differential calorimetric analysis confirmed drug-polymer integration in all formulations, and X-ray powder diffraction showed both chitosan and HPMC formulations as crystalline configuration. The formulations with the highest in vitro release were LT4-HPMC 1:3 and LT4-chitosan 1:5. Conclusions: Results of this study suggest that both chitosan and HPMC can be used as sustained release polymers for the intranasal delivery of LT4.

scholarly journals DEVELOPMENT AND CHARACTERIZATION OF DOXORUBICIN AND siRNA ENCAPSULATED CHITOSAN NANOPARTICLES

2020 ◽  
pp. 53-56
Author(s):  
TAIHASEEN MOMIN ◽  
ARVIND GULBAKE
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Encapsulation Efficiency ◽  
Chitosan Nanoparticles ◽  
In Vitro Release ◽  
Burst Release ◽  
Transmission Electron Micrograph ◽  
Cancer Breast ◽  
Gel Retardation

Objective: Chitosan nanoparticles (ChNP’s) have been widely studied for drug and gene delivery. In this study, we prepared ChNP’s for co-delivery of doxorubicin (DOX) and siRNA for cancer treatment. Methods: The ionic gelation method was used to develop ChNP’s. The positively charged DOX and negatively charged siRNA encapsulated into ChNP’s. The particle size and zeta potential of the developed ChNP’s were studied by particle size analyzer and morphology was examined by TEM. Encapsulation of DOX in ChNP’s was confirmed by FTIR spectroscopy. The encapsulation efficiency and in vitro release of DOX were studied by UV-Vis spectrophotometry. The siRNA loading into ChNP’s was confirmed by gel retardation assay. Results: The developed ChNP’s showed particle size ranged from 127±6.5 to 215±8.5 nm with zeta potential ranged from 16.5±0.3 to 25.8±0.3. Transmission Electron Micrograph showed DOX and siRNA encapsulated ChNP’s are polydisperse and spherical in nature. FTIR study confirmed the binding of DOX with ChNP’s with absorption peaks at 1016 cm-1,1316 cm-1, 1412 cm-1, 1645 cm-1 and 3370 cm-1. The TPP:Ch ratio 0.1:0.5 showed the highest encapsulation efficiency 69±3.24%, with initial burst release and then sustained or slow release of DOX. Agarose gel retardation study confirmed the encapsulation of siRNA in ChNP’s by retarded migration of siRNA-ChNP’s in comparison with naked siRNA. Conclusion: The developed ChNP’s successfully encapsulated the DOX and siRNA and showed the sustain release of DOX. In conclusion, our study shown that ChNP’s is having a potential of co-loading of DOX-siRNA as an efficient drug delivery system for the treatment of various cancers such as colorectal cancer, breast cancer etc.

scholarly journals SELF-ASSEMBLED CHITOSAN NANOPARTICLES FOR PERCUTANEOUS DELIVERY OF CAFFEINE: PREPARATION, CHARACTERIZATION AND IN VITRO RELEASE STUDIES

2018 ◽  
Vol 10 (4) ◽  
pp. 172 ◽  
Author(s):  
Nik Amanina Farhanah Abu Hassan ◽  
Shariza Sahudin ◽  
Zahid Hussain ◽  
Mumtaz Hussain ◽  
Mumtaz Hussain
Keyword(s):  
Electron Microscopy ◽  
Particle Size ◽  
Zeta Potential ◽  
Surface Charge ◽  
Process Parameters ◽  
In Vitro Release ◽  
Freeze Dried ◽  
Release Studies ◽  
Vitro Release

Objective: Chitosan (CS)–tripolyphosphate (TPP)–nanoparticles (NPs) have been extensively studied during the past few decades due to their well-recognized applicability in various fields. The present study attempts to optimise the development of these nanoparticles to enhance the percutaneous delivery of caffeine.Methods: CS-TPP-NPs were prepared via ionic cross-linking of CS and TPP and were characterized. The influence of several formulation conditions (CS: TPP mass ratio and concentration of caffeine) and process parameters (stirring speed, stirring time and ultra-sonication time) on the colloidal characteristics of CS-TPP-NPs were investigated and the resulting nanoparticles were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) and x-ray diffraction (XRD) analyses. Physicochemical properties, including particle size, zeta potential and polydispersity index (PDI) were examined, and in vitro release studies were conducted to ascertain the release profile of caffeine from the nanoparticles. In addition, the colloidal stability of the prepared NPs was also assessed on storage.Results: Process parameters appeared to exert a significant effect on the physicochemical characteristics of the CS-TPP-NPs. The CS-TPP-NPs prepared under optimum conditions (CS concentration of 0.2 mg/ml, CS: TPP volume ratio of 25:12 ml, stirred at 700 rpm for 60 min, with 0.97 mg/ml caffeine concentration and treatment with low ultra-sonication for 30 min) had shown a mean particle size of ~143.43±1.69 nm, zeta potential of+43.13±1.10 mV, PDI of ~0.30±0.01. A drug loading capacity and encapsulation efficiency of 48.89% and 60.69%, respectively, were obtained. Cumulative release study for drug-loaded CS-NPs was significantly (p<0.001, paired t-test) higher (58.7% caffeine released) compared to control formulation (41.5% caffeine released) after 72 h. Stability studies conducted for 28 d showed that caffeine-loaded CS-NPs degraded much quicker when stored at 25 ⁰C than 4 ⁰C. It was also noted that caffeine-loaded CS-NPs in the freeze-dried form were unstable as the surface charge of nanoparticles dropped from positive zeta potential to-3.55 mV within 2 d at 4 ⁰C and at 25 ⁰C, surface charge dropped to-3.16 mV within 14 d of the experiment.Conclusion: Chitosan (CS)–tripolyphosphate (TPP)–nanoparticles (NPs) appear to be a promising strategy to achieve sustained percutaneous delivery of caffeine.

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