Protein-based microneedles for biomedical applications: A systematic review.

Microneedles are minimally-invasive devices with the unique capability of bypassing physiological barriers. Hence, they are widely used for different applications from drug/vaccine delivery to diagnosis and cosmetic fields. Recently, natural biopolymers (particularly carbohydrates and proteins) have garnered attention as safe and biocompatible materials with tailorable features for microneedle construction. Several review articles have dealt with carbohydrate-based microneedles. This review aims to highlight the less-noticed role of proteins through a systematic search strategy based on the PRISMA guideline from international databases of PubMed, Science Direct, Scopus, and Google Scholar. Original English articles with the keyword "microneedle(s)" in their titles along with at least one of the keywords "biopolymers, silk, gelatin, collagen, zein, keratin, fish-scale, mussel, and suckerin" were collected and those in which the proteins undertook a structural role were screened. Then, we focused on the structures and applications of protein-based microneedles. Also, the unique features of some protein biopolymers that make them ideal for microneedle construction (e.g., excellent mechanical strength, self-adhesion, and self-assembly), as well as the challenges associated with them were reviewed. Altogether, the proteins identified so far seem not only promising for the fabrication of "better" microneedles in the future but also inspiring for designing biomimetic structural biopolymers with ideal characteristics.

Skin permeability, a dismissed necessity for anti-wrinkle peptide performance.

BACKGROUND: The skin offers various benefits and potential for peptide delivery if its barrier performance can be reduced temporarily and reversibly. As peptides possess high molecular weight, hydrophilic nature (in most cases), and ionizable groups in the structure, their skin delivery is highly challenging. Apart from this, they are susceptible to the proteolytic enzymes in the skin. Anti-wrinkle peptides, like other peptides, suffer from insufficient skin permeability, while most of them must penetrate deep in the skin to present their efficacy. Although the cellular studies indicate the effectiveness of such peptides, without the ability to permeate the skin sufficiently, this efficacy is useless. Poor skin permeability of anti-wrinkle peptides has led to ongoing research for finding feasible and noninvasive enhancement methods that would be desirable for consumers of cosmetic products. METHOD: In this paper, the possibility of skin permeation of anti-wrinkle peptides as well as the chemical, physical, and encapsulation approaches that have been employed to date to increase permeability of these difficult molecules are thoroughly reviewed. RESULTS: Most anti-wrinkle peptides are not appropriate candidates for skin permeation and the use of enhancement methods is essential to increase their permeability. To do so, only some permeability enhancement approaches have been applied so far, including chemical modification with hydrophobic moieties or cell penetrating peptides, metal complexation, chemical permeation enhancers, iontophoresis, microneedles, and encapsulation in nanocarriers. The results of studies published on the skin permeability of anti-wrinkle peptides carnosine, GHK, PKEK, GEKG, GQPR, and KTTKS indicate that the skin permeability of these peptides can be successfully increased. CONCLUSION: Although the skin permeability of most anti-wrinkle peptides is not high enough and most anti-wrinkle peptides might not reach their targets in the skin at right concentrations, their permeability can be increased to therapeutic concentrations using various enhancement approaches.

CONTEXTE: La peau offre divers avantages et a la faculté de recevoir des peptides si l'on parvient à réduire temporairement et de manière réversible sa capacité à fonctionner comme une barrière. Comme les peptides ont un poids moléculaire élevé, une nature hydrophile (dans la plupart des cas) et possèdent des groupes ionisables dans leur structure, il est très difficile d'en faire bénéficier la peau. En outre, ils sont sensibles aux enzymes protéolytiques de la peau. Les peptides antirides, comme d'autres peptides, souffrent d'une capacité insuffisante de perméation de la peau ; or, la plupart d'entre eux doivent y pénétrer profondément pour avoir une efficacité. Bien que les études cellulaires indiquent l'efficacité de ces peptides, s'ils sont incapables de pénétrer suffisamment la peau, cette efficacité est inopérante. Face à cette perméabilité médiocre de la peau aux peptides antirides, des recherches sont menées actuellement pour trouver des méthodes d'amélioration à la fois réalisables et non invasives, qui soient attractives pour les consommateurs de produits cosmétiques. MÉTHODE: Dans cet article, nous étudions de manière approfondie la possibilité de perméation des peptides antirides à travers l'épiderme, ainsi que les approches chimiques, physiques et d'encapsulation utilisées à ce jour pour augmenter l'aptitude à la perméation de ces molécules difficiles. RÉSULTATS: La plupart des peptides antirides ne sont pas de bons candidats à la perméation de l'épiderme, et il est essentiel d'avoir recours à des méthodes de renforcement pour augmenter leur capacité de pénétration. Pour ce faire, seules certaines approches de renforcement de la perméation ont été appliquées jusqu'à présent : une modification chimique avec des fractions hydrophobes ou des peptides pénétrants la cellule ; la complexation métallique ; les amplificateurs de perméation chimique ; l'iontophorèse ; les micro-aiguilles et l'encapsulation dans les nano supports. Les résultats des études publiées sur la perméabilité de l'épiderme aux peptides antirides que sont la carnosine, le GHK, le PKEK, le GEKG, le GQPR et le KTTKS indiquent que l'augmentation de la capacité de perméation de l'épiderme de ces peptides est possible et donne de bons résultats. CONCLUSION: Bien que la capacité de perméation de la plupart des peptides antirides ne soit pas suffisamment élevée et qu'ils n'atteignent pas leurs cibles dans la peau aux bonnes concentrations, cette capacité peut être augmentée jusqu'à des concentrations thérapeutiques en recourant à diverses approches de renforcement.

Investigating the Changes in Cream Properties Following Topical Application and Their Influence on the Product Efficiency.

Topical products are not stable following application to the skin due to the evaporation of volatile components. Such changes have been demonstrated in liquid emulsions, but there is almost no study available for creams in this respect. The aim of the present investigation is to evaluate the changes in cream properties following topical application and their influence on product efficiency. A method has also been designed and validated to mimic cream application to the skin. To perform this investigation, five different creams were prepared and alterations of type of creams, size of droplets of the dispersed phase, occlusivity, water content and rate of water loss were studied after application. These changes were then attributed to the type of cream, water content, presence of humectant, and time post application. The results demonstrated that creams changed intensely after application, including the phase inversion of O/W formulations, changes in the occlusivity of creams, reduction of water content, rate of water evaporation and droplet size. Such changes could be controlled partly by humectants. The present results suggest that formulators should be aware of such possible changes and required precautions should be taken in advance.

Propranolol Hydrochloride Buccoadhesive Tablet: Development and In-vitro Evaluation.

Propranolol HCl is a beta blocker commonly used worldwide; however, it shows a low bioavailability due to its extensive first-pass metabolism. To overcome this problem, a novel drug delivery system such as buccoadhesive system might be helpful. The aim of the present investigation is to prepare the buccoadhesive tablet of propranolol HCl using different mucoadhesive polymers. Buccoadhesive tablets containing drug, lactose, and polymers such as HPMC K4M, carbomer 934P, PEO 8000000 and PEG 6000, in various concentrations, were prepared. The tablets were evaluated in terms of weight variation, thickness, hardness, friability, and mucoadhesive strength. Among thirteen prepared formulations, seven of them which had better physicochemical properties and mucoadhesive strength were undergone the release and swelling tests. Finally, two formulations were selected and uniformity, drug content, duration of mucoadhesion, and kinetic studies were performed for them. All polymers except PEG 6000 were appropriate for being used in buccal mucoadhesive systems. Formulation F1 was considered as the most desirable formulation as it exhibited appropriate mucoadhesive strength (43.93 ± 12.4 g), extended duration of mucoadhesion (19.15 ± 0.29 h) and suitable swelling ability while having a prolonged drug release over 12 h. Although the efficiency and mucosal irritation of propranolol HCl buccoadhesive tablets should be monitored under the in-vivo conditions, however, based on the results, it seems that such tablets can be considered as an alternative route to bypass the first pass metabolism of propranolol HCl.

Intra tester reliability of sympathetic skin responses in subjects with primary palmar hyperhidrosis.

BACKGROUND: Primary palmar hyperhidrosis (PPH) is a disorder related to sympathetic dysfunction. Iontophoresis can be used to reduce sweating rate. Sympathetic skin response (SSR) is commonly used to evaluate the sympathetic system. However, scarce evidence exists about the reliability of SSR parameters. OBJECTIVE: To assess the relative and absolute reliability of SSR before and after the application of iontophoresis with aluminum chloride hexahydrate (ACH) gel or tap water in subjects with PPH. METHODS: Twenty subjects were randomized to receive either iontophoresis with ACH gel or tap water. Three SSRs (amplitude and latency) with 5 s intervals from both hands in both groups were recorded before and after the application of iontophoresis for 30 min. Reliability of amplitude and latency of the SSR was assessed using intraclass correlation coefficient (ICC) with 95% confidence intervals, standard error of measurement (SEM), and minimal detectable change (MDC). RESULTS: Amplitudes and latencies of SSR showed good to excellent test-retest reliability for ICC in both groups before iontophoresis. Except for right hand latency which was moderate (0.5-0.75). After iontophoresis, the ACH gel group still showed good to excellent agreement for SSR parameters, while the reliability of SSR parameters in the tap water group was reduced. CONCLUSION: Subjects with PPH showed high intra-rater reliability for SSR parameters which was maintained after ACH gel iontophoresis and decreased after tap water iontophoresis. It seems that media used for iontophoresis or the state of media (gel vs liquid) may affect the reliability of SSR. Further research is recommended.

Effect of Palmitic Acid Conjugation on Physicochemical Properties of Peptide KTTKS: A Preformulation Study.

Lys-Thr-Thr-Lys-Ser (KTTKS) minimally crosses the skin because of hydrophilicity; therefore, its palmitoyl derivative, palmitoyl-KTTKS (Pal-KTTKS), is used in cosmetic products. In spite of this, there is insuffi cient information on its physicochemical properties and the effects of palmitoylation on such properties. The aim of this study was to investigate these properties. Such information would help appropriate formulation development. KTTKS and Pal-KTTKS were synthesized and characterized for ultra violet (UV) absorption, structure [X-ray diffraction (XRD)], morphology (electron microscopy), birefringence (polarized light microscopy), partitioning,solubility, thermal behavior (melting, thermogravimetric analysis, and differential scanning calorimetry), surface activity, critical micelle concentration (CMC, by tensiometry), and stability. KTTKS and Pal-KTTKS decomposed at about 154 and 150°C, respectively, and did not show a melting point before decomposition. The maximum UV absorbance of peptides was less than 200 nm. Both peptides showed birefringence, irregular flake morphologies, and hygroscopicity. KTTKS was freely soluble in water at room temperature (logP = -1.6 ± 0.15), indicating its hydrophilic nature. logP of Pal-KTTKS was calculated to be about 3.7, indicating a lipophilic compound. Pal-KTTKS showed surface activity with a CMC value of 0.024 ± 0.004 mM (19.25 ± 2.9 mg/L),whereas KTTKS did not show such surface activity. Palmitoylation demonstrated sharp peaks in the XRD pattern of KTTKS. KTTKS and Pal-KTTKS differ mainly in terms of chemical properties and show some similarity in physical properties. These results can be used for formulation developments.