Soft Malleable Vesicles: versatile carriers for efficient topical delivery of fungal therapeutics

Drug Research ◽  
2020 ◽  
Author(s):  
Preeti Gupta ◽  
Antesh Kumar Jha ◽  
Mahesh Prasad ◽  
Poonam Kushwaha

AbstractFungal infections have become a subject of great concern and the incidence of fungal infections is increasing, presenting an enormous challenge to healthcare professionals. Since most of the fungal infections are occurring over the skin, the treatment option of these infections always involves topical application. However, in topical delivery drug reaches into systemic circulation through different barriers of skin. Nevertheless, due to the low permeability, skin restricts the movement of many drugs. Hence, a delivery system is required, which deliver the medicament into the skin layers or through the skin and into the systemic circulation. Ethosomes or Soft malleable vesicles are the novel lipid vesicular carrier that offer improved skin permeability and efficient delivery due to their structure and composition. They contain high concentration of ethanol, which increases the fluidity of the skin. Therefore, in the present paper, we have explored the utility of ethosomal systems in the topical treatment of fungal infections. Structure, compositions types, mechanism and techniques of preparation of ethosome also discussed in the paper.

2011 ◽  
Vol 694 ◽  
pp. 881-885
Author(s):  
Xin He ◽  
Xing Hua Zhao ◽  
Wu Qing Ou Yang

The purpose of this study was to explore the potential application of the combination of microemulsion as a topical delivery vehicle in enhancing the absorption and efficacy of tripterygium wilfordii multiglycoside (TWM). Various microemulsion formulations were developed and an optimal microemulsion (TWM-ME),which presented spherical droplets and consisted of RH-40, IPM and water was 27: 3.3: 69.7 by weight. It possessd an average droplet size of 23.6 nm, a low viscosity of (3.56±0.12) mm2•s-1 Zeta electric potential was (–5.35±0.42) mV, refractive index was (1.3617±0.0051) nD20, conductivity was (97.6±3.6) μs/cm. Compared to the control solution, TWM-ME provided better skin permeability in vitro. Moreover, TWM-ME has noticeable anti-inflammatory and immune suppression effect. These results indicate that the combination of microemulsion represents an effective vehicle for topical delivery of TWM.


1982 ◽  
Vol 100 (2) ◽  
pp. 279-284 ◽  
Author(s):  
R. C. Arora ◽  
R. S. Pandey

Abstract. Domestic buffaloes were used to characterize the pattern of progesterone, oestradiol-17β, LH and androgen in the systemic circulation following infertile insemination. Concentrations of hormones were measured by RIA in blood samples collected daily or at alternate days following insemination. The concentration of progesterone was lowest on the day of insemination, and increased significantly to a peak level of 4.00 ± 0.60 ng/ml by day 13 post insemination. After day 17, it declined significantly (P < 0.01) to reach low levels by day 21. The concentration of oestradiol-17β was high at the time of insemination and declined significantly (P < 0.01) by day 2 after insemination. It was maintained around the basal level till day 18 with minor peaks in between this period. It again rose significantly (P < 0.01) at subsequent oestrus. The mean level of LH was highest at the time of insemination, and declined significantly (P < 0.01) by day 1 post insemination. It did not vary appreciably till the animal returned to oestrus. The oestrous value of LH and progesterone were negatively correlated (r = −0.77). The androgen level was observed to be high at insemination in 3 out of 5 animals, but the overall pattern of this steroid was inconsistent during the period studied. A high concentration of androgen was recorded in all the animals from day 2–5 before the onset of oestrus.


2021 ◽  
Author(s):  
Moataz Dowaidar

Gastric cancer is the world's second-largest death cause. Developing suitable medical therapies can help individuals live longer. So far, GC treatment has depended on several pharmaceutical techniques. Chemotherapy and surgery are GC patients' most frequent treatment choices. The most major hurdles to effective GC therapy are chemotherapeutic resistance and non-selective targeting. Recent GC-targeted therapeutic research has focused on building more selective and effective anti-GC pharmacological approaches. Because molecular focused therapy can greatly exacerbate the current inefficacy of normal GC therapy procedures, peptide base synthesis can be used as a carrier to deliver radiation or other fatal chemicals to tumor locations with precise protein overexpression. Different types of peptides with special binding affinity to GC overexpressed receptors have been identified for targeted therapy and imaging. Although some of these peptides have excellent GC targeting ability, they also need great GC penetration capacity and no systemic in vivo toxicity before they can be employed in clinical studies. One of these peptides' most notable limitations is their short plasma half-life, limiting their efficient delivery to tumor locations. Sluggish binding pharmacokinetics, along with in vivo instability, can produce targeted treatment failure. Using an appropriate modification strategy to boost blood circulation time may be advantageous.The key to producing successful, innovative anti-cancer targeting drugs with specific targeting capabilities is to mark the peptide with distinct diagnostic and therapeutic radioisotopes. Although a peptide's radiolabeling or enzymatic degradation may not affect its targeting capabilities, the radiation dose delivery impact on it is obvious. Selecting an appropriate type of radionuclide to achieve high-specific activity, using a simple and high-efficiency radiolabeling process, and selecting an adequate spacer and chelator to manage peptide biodistribution are all important considerations when designing a peptide-based radiopharmaceutical. High internalization and significant systemic circulation washout are other essential tumor targeting needs. Many of the peptides described in this work lack these critical features. The radiolabeled peptide should also remain intact and have a short blood washout period, allowing targeted imaging and therapy. SPECT and PET are the most extensively used technologies in nuclear medicine. Although PET has a greater resolution, SPECT technology gives a comparable sensitivity at a lesser cost. Combining fast binding pharmacokinetics with suitable stability in vivo can result in efficient tumor contrast. Non-target liver and kidney accumulation is required when employing radiolabeled peptides to target GC. When a radiolabeled peptide accumulates more in the liver and intestine than in the GC tumor, the image quality degrades. However, using the proper chelator and spacer can assist decrease non-target accumulation in the kidneys. Finally, considering all these conditions and being positive, it is conceivable to produce a unique peptide with avid binding to GC cells.


1992 ◽  
Vol 30 (12) ◽  
pp. 47-48

Most common fungal infections of the skin respond to topical treatment but dermatophytosis (ringworm; tinea) is sometimes an exception; ringworm of the body or groin usually clears (e.g. with a topical azole) but dermatophyte infections of the nails, the hair and scalp, or of the soles and palms, generally need systemic therapy. This has traditionally been with griseofulvin but length of treatment, low rates of lasting cure and unwanted effects are drawbacks. Terbinafine (Lamisil – Sandoz) is a new systemic antifungal intended for the treatment of dermatophyte infections in adults. The manufacturer claims it achieves a high cure rate and low rate of relapse with only brief treatment periods. How useful is it?


2019 ◽  
Vol 38 (4) ◽  
pp. 1085-1095
Author(s):  
Jeroen Roosendaal ◽  
Hilde Rosing ◽  
Luc Lucas ◽  
Abadi Gebretensae ◽  
Alwin D. R. Huitema ◽  
...  

Summary Purpose The objective of this mass balance trial was to determine the excretory pathways and metabolic profile of the novel anticancer agent guadecitabine in humans after administration of a 14C-radiolabeled dose of guadecitabine. Experimental design Included patients received at least one cycle of 45 mg/m2 guadecitabine subcutaneously as once-daily doses on Days 1 to 5 of a 28-day cycle, of which the 5th (last) dose in the first cycle was spiked with 14C-radiolabeled guadecitabine. Using different mass spectrometric techniques in combination with off-line liquid scintillation counting, the exposure and excretion of 14C-guadecitabine and metabolites in the systemic circulation, excreta, and intracellular target site were established. Results Five patients were enrolled in the mass balance trial. 14C-guadecitabine radioactivity was rapidly and almost exclusively excreted in urine, with an average amount of radioactivity recovered of 90.2%. After uptake in the systemic circulation, guadecitabine was converted into ß-decitabine (active anomer), and from ß-decitabine into the presumably inactive metabolites M1-M5. All identified metabolites in plasma and urine were ß-decitabine related products, suggesting almost complete conversion via cleavage of the phosphodiester bond between ß-decitabine and deoxyguanosine prior to further elimination. ß-decitabine enters the intracellular activation pathway, leading to detectable ß-decitabine-triphosphate and DNA incorporated ß-decitabine levels in peripheral blood mononuclear cells, providing confirmation that the drug reaches its DNA target site. Conclusion The metabolic and excretory pathways of guadecitabine and its metabolites were successfully characterized after subcutaneous guadecitabine administration in cancer patients. These data support the clinical evaluation of safety and efficacy of the subcutaneous guadecitabine drug product.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Kaisar Raza ◽  
Manish Kumar ◽  
Pramod Kumar ◽  
Ruchi Malik ◽  
Gajanand Sharma ◽  
...  

Osteoarthritis (OA), a common musculoskeletal disorder, is projected to affect about 60 million people of total world population by 2020. The associated pain and disability impair the quality of life and also pose economic burden to the patient. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed in OA, while diclofenac is the most prescribed one. Oral NSAIDs are not very patient friendly, as they cause various gastrointestinal adverse effects like bleeding, ulceration, and perforation. To enhance the tolerability of diclofenac and decrease the common side effects, aceclofenac (ACE) was developed by its chemical modification. As expected, ACE is more well-tolerated than diclofenac and possesses superior efficacy but is not completely devoid of the NSAID-tagged side effects. A series of chemical modifications of already planned drug is unjustified as it consumes quanta of time, efforts, and money, and this approach will also pose stringent regulatory challenges. Therefore, it is justified to deliver ACE employing tools of drug delivery and nanotechnology to refine its safety profile. The present review highlights the constraints related to the topical delivery of ACE and the various attempts made so far for the safe and effective topical delivery employing the novel materials and methods.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ke-dong Xu ◽  
Wei Wang ◽  
De-shui Yu ◽  
Xiao-li Li ◽  
Jia-min Chen ◽  
...  

AbstractThe novel methods for efficient plant regeneration via direct somatic embryogenesis (SE) and SE-mediated transformation system under high concentration of NAA in Ranunculus sceleratus were established. On MS media containing a high concentration of NAA (10.0 mg/L) in the dark, all inoculated explants (root, stem and leaf) formed somatic embryos at high frequencies, respectively, 66.03, 126.47 and 213.63 embryoids per explant, and 100% of the embryoids developed into plantlets on 1/2 MS rooting media. Morphological and histological analyses revealed that SE in R. sceleratus followed a classical pattern. All inoculated explants can be used as receptors for genetic transformation in R. sceleratus, through direct SE-mediated method after Agrobacterium infection. RcLEC1-B, as a marker gene, changed the number and morphology of flower organs and the development of cuticle in R. sceleratus, which indicated that the efficient transgenic system of R. sceleratus was established. To our knowledge, this is the first observation that both direct SE and transgenic transformation system, via induction of a single plant growth regulator, have been successfully constructed in R. sceleratus.


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