scholarly journals Asymmetry in Drug Permeability through the Cornea

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 694
Author(s):  
Nadia Toffoletto ◽  
Anuj Chauhan ◽  
Carmen Alvarez-Lorenzo ◽  
Benilde Saramago ◽  
Ana Paula Serro

The permeability through the cornea determines the ability of a drug or any topically applied compound to cross the tissue and reach the intraocular area. Most of the permeability values found in the literature are obtained considering topical drug formulations, and therefore, refer to the drug permeability inward the eye. However, due to the asymmetry of the corneal tissue, outward drug permeability constitutes a more meaningful parameter when dealing with intraocular drug-delivery systems (i.e., drug-loaded intraocular lenses, intraocular implants or injections). Herein, the permeability coefficients of two commonly administered anti-inflammatory drugs (i.e., bromfenac sodium and dexamethasone sodium) were determined ex vivo using Franz diffusion cells and porcine corneas in both inward and outward configurations. A significantly higher drug accumulation in the cornea was detected in the outward direction, which is consistent with the different characteristics of the corneal layers. Coherently, a higher permeability coefficient was obtained for bromfenac sodium in the outward direction, but no differences were detected for dexamethasone sodium in the two directions. Drug accumulation in the cornea can prolong the therapeutic effect of intraocular drug-release systems.

2018 ◽  
Vol 2 (5) ◽  
pp. 01-04
Author(s):  
Collin Jared ◽  
Diego Luis ◽  
Jonathan Noah ◽  
Benjamin Dylan

Aim: The purpose of the study was to characterize transdermal delivery of xenon through rat skin from a lipophilic solution and from water. Methods: Sections of skin were obtained from adult rats (n=12) and were placed into static Franz diffusion cells for 24 h. Xenon diffusion coefficients were determined for diffusion from a lipophilic solution (n=6) and from water (n=6) to phosphate buffered saline (PBS) through skin and for diffusion from a lipophilic solution to PBS through a phase boundary in the absence of skin (n=6). Results: Xenon flux (JXe) through skin from the lipophilic solution was 0.036 mg/hour×cm2 and permeability coefficient (Kp) was 0.003 cm/h; JXe through skin from water was 0.029 mg/h×cm2 and the Kp was 0.002 cm/h. Total time for xenon diffusion through skin from lipophilic solution and from water was ~2 h. Conclusion: The study presents the first characterization of xenon diffusion through rat skin from multiphase solutions to PBS. These data may be useful for the development of xenon-rich pharmaceutical products for external use.


Author(s):  
Jorge L Alio ◽  
Pablo Sanz-Díez

ABSTRACT Purpose To discuss and summarize the indications, contraindications and results in refractive surgery for keratoconus. Summary Keratoconus is an ectatic corneal disease characterized by a progressive corneal thinning and irregular astigmatism that negatively impact in the visual function and the optical quality of the patients. The refractive surgery in keratoconus has been discussed by several authors. The two primary lines of action are phakic lens implantation and corneal tissue ablation using photorefractive keratectomy. The use of phakic intraocular lenses (IOLs) to correct myopia and compound myopic astigmatism associated with keratoconus is gaining popularity. Recent findings The use of phakic IOLs to correct myopia and compound myopic astigmatism associated with keratoconus is gaining popularity. According to a recent study by our group the safety of this procedure in visual terms is high (post-CDVA/ pre-CDVA = 1.19 ± 0.29). It is also an effective operation (post-UDVA/pre-CDVA = 0.90 ± 0.26). How to cite this article Alio JL, Sanz-Díez P. Phakic Intraocular Lenses in Keratoconus. Int J Kerat Ect Cor Dis 2015;4(3):103-106.


Author(s):  
Mansi L. Patil ◽  
Swati S. Gaikwad ◽  
Naresh J. Gaikwad

Introduction: Pain is an immunological response to any infection or inflammation and long term use of pain management therapy includes use of Nonsteroidal anti-inflammatory drugs which is associated with occurrence of toxicity as well as gastrointestinal bleeding. Therefore, the investigation of new analgesic and anti-inflammatory agents remains a major challenge. Aims: The objective of this research study is to undergo the pharmacological evaluation of newly synthesized benzoxazole derivatives. These novel derivatives were evaluated for anti-nociceptive, anti-inflammatory and cytotoxic activity using various in-vivo and ex-vivo methods. Methods: The study was carried out using swiss mice (adult male) weighing between 20gm to 30gm and were divided into groups containing (n=6) six animals in each group for treatment. The anti-nociceptive activity was performed by using 0.1ml of 0.6% v/v acetic acid as nociception inducer and evaluated by the diminished number of abdominal writhes. The anti-inflammatory activity was done using 0.1 ml of 2% w/v Carrageenan induced paw edema method was observed which was evaluated by calculating the percent maximum possible effect. Histopathological evaluation and cytotoxic activity of the compounds was carried out. Results: The results of this research study revealed that synthesized derivatives (a, b, c, d and e) showed promising anti-nociceptive and anti-inflammatory effect along significantly higher cytotoxic activity in MCF-7 cell lines. Conclusion: It can be concluded that synthesized derivatives (a, b, c, d and e) have potential anti-nociceptive and anti-inflammatory effect along with cytotoxic activity and certain modification in structure may result in potent activity.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 282 ◽  
Author(s):  
Julia Zhang ◽  
Anna Froelich ◽  
Bozena Michniak-Kohn

The aim of this study is to develop, characterize and compare conventional liposome, deformable liposome (transfersome) and microemulsion formulations as potential topical delivery systems for meloxicam. Liposomes were characterized in terms of vesicle size, zeta potential and entrapment efficiency. For microemulsions, particle size, electrical conductivity and viscosity studies were performed to assess the structure of the investigated systems. An ex vivo skin permeation study has been conducted to compare these formulations. The dermal and transdermal delivery of meloxicam using these formulations can be a promising alternative to conventional oral delivery of non-steroidal anti-inflammatory drugs (NSAIDs) with enhanced local and systemic onset of action and reduced side effects.


Pharmaceutics ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 426
Author(s):  
Fernández-Campos ◽  
Clares ◽  
Rodríguez-Lagunas ◽  
Jauregui ◽  
Casals ◽  
...  

Rhinosinusitis is a prevalent disorder with a severe impact on the health-related quality of life. Saponins of Cyclamen europaeum exert a clinically proven curative effect on rhinosinusitis symptoms when instilled into the nasal cavity, however, more extensive preclinical assessment is required to better characterize the efficacy of this botanical extract. This work evaluates the potential use of a natural freeze-dried extract of C. europaeum given as topical nasal administration. Permeation experiment on porcine nasal mucosa was performed with Franz diffusion cells. Experiments in rabbits were performed to test for any toxicological, hematological, biochemical or histological evidence of systemic action. No theoretical levels of saponins were found in the receptor chamber of Franz diffusion cells. Hematological data did not show significant differences between control and experimental animals (p > 0.05). Histological studies also showed that enhanced secretory activity in response to intranasal administration was not accompanied by any visible signs of injury. An examination of the brain, lungs, liver, kidneys, spleen, and gastrointestinal organs did not reveal any abnormality. The absence of mucosal permeation of saponins and negligible probability of C. europaeum saponins absorption in the course of a therapeutic application was demonstrated.


2018 ◽  
Vol 21 (1s) ◽  
pp. 48s-73s ◽  
Author(s):  
Zuhair Alqahtani ◽  
Fakhreddin Jamali

Purpose: Concomitant use of some non-Aspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) reduces the extent of platelet aggregation of Aspirin (acetylsalicylic acid). This is while many observational studies and clinical trials suggest that Aspirin reduces cardiovascular (CV) risk attributed to the use of NANSAIDs. Thus, the therapeutic outcome of the interaction needs to be assessed. Methods: We searched various databases up to October 2017 for molecular interaction studies between the drugs and long-term clinical outcomes based on randomized clinical trials and epidemiological observations that reported the effect estimates of CV risks (OR, RR or HR; 95% CI) of the interacting drugs alone or in combinations. Comparisons were made between outcomes after Aspirin alone, NANSAIDs alone and Aspirin with naproxen, ibuprofen, celecoxib, meloxicam, diclofenac or rofecoxib. Results: In total, 32 eligible studies (20 molecular interactions studies and 12 observational trials) were found. Conflicting in vitro/in vivo/ex vivo platelet aggregation data were found for ibuprofen, naproxen and celecoxib. Nevertheless, for naproxen, the interaction at the aggregation level did not amount to a loss of cardioprotective effects of Aspirin. Similarly, for ibuprofen, the results overwhelmingly suggest no negative clinical CV outcomes following the combination therapy. Meloxicam and rofecoxib neither interacted with Aspirin at the level of platelet aggregation nor altered clinical outcomes. The clinical outcomes data for celecoxib and diclofenac are in conflict. Conclusion: Aspirin appears to maintain its cardioprotective effect in the presence of naproxen, ibuprofen, meloxicam and rofecoxib. The limited available data suggest that the effect of interaction at the platelet aggregation level may dissipate shortly, or the reduced platelet aggregation yielded by the interaction may be sufficient for cardioprotection; i.e., no need for near complete aggregation. In addition, cardioprotective effect of Aspirin, despite reduced platelet aggregation caused by NANSAIDs, may be through its involvement in other mechanisms such as the renin-angiotensin system and/or metabolism of arachidonic acid to biologically active compounds mediated by cytochrome P450. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.


Reproduction ◽  
2014 ◽  
Vol 147 (3) ◽  
pp. 313-320 ◽  
Author(s):  
Lisa F Stinson ◽  
Demelza J Ireland ◽  
Matthew W Kemp ◽  
Matthew S Payne ◽  
Sarah J Stock ◽  
...  

Intrauterine infection and inflammation are responsible for the majority of early (<32 weeks) spontaneous preterm births (PTBs). Anti-inflammatory agents, delivered intra-amniotically together with antibiotics, may be an effective strategy for preventing PTB. In this study, the effects of four cytokine-suppressive anti-inflammatory drugs (CSAIDs:N-acetyl cysteine (NAC), SB239063, TPCA-1 and NEMO binding domain inhibitor (NBDI)) were assessed on human and ovine gestational membrane inflammation. Full-thickness membranes were collected from healthy, term, human placentas delivered by Caesarean section (n=5). Using a Transwell model, they were stimulatedex vivowith γ-irradiation-killedEscherichia coliapplied to the amniotic face. Membranes from near-term, ovine placentas were stimulatedin uterowith lipopolysaccharide,Ureaplasma parvumor saline control and subjected to explant culture. The effects of treatment with CSAIDs or vehicle (1% DMSO) on accumulation of PGE2and cytokines (human interleukin 6 (IL6), IL10 and TNFα; ovine IL8 (oIL8)) were assessed in conditioned media at various time points (3–20 h). In human membranes, the IKKβ inhibitor TPCA-1 (7 μM) and p38 MAPK inhibitor SB239063 (20 μM) administered to the amniotic compartment were the most effective in inhibiting accumulation of cytokines and PGE2in the fetal compartment. NAC (10 mM) inhibited accumulation of PGE2and IL10 only; NBDI (10 μM) had no significant effect. In addition to the fetal compartment, SB239063 also exerted consistent and significant inhibitory effects in the maternal compartment. TPCA-1 and SB239063 suppressed oIL8 production, while all CSAIDs tested suppressed ovine PGE2production. These results support the further investigation of intra-amniotically delivered CSAIDs for the prevention of inflammation-mediated PTB.


2012 ◽  
Vol 191 (3) ◽  
pp. 327-333 ◽  
Author(s):  
B. Cuniberti ◽  
R. Odore ◽  
R. Barbero ◽  
P. Cagnardi ◽  
P. Badino ◽  
...  

2018 ◽  
Author(s):  
Ricardo M. Gouveia ◽  
Guillaume Lepert ◽  
Suneel Gupta ◽  
Rajiv R. Mohan ◽  
Carl Paterson ◽  
...  

SummaryWhilst the control of stem cell differentiation using substrates of differing compliance has been extensively explored in vitro, the significance of this mechanism at a physiological level is not known. Here we set to explore the role of corneal surface biomechanics in controlling epithelial cell proliferation and differentiation. Using non-contact high-resolution Brillouin spectro-microscopy we showed that the corneal outer edge (limbus) has significantly lower bulk modulus compared to the central cornea, and that this difference is precisely delimited in the organ. Furthermore, the areas of the limbus with distinctly softer properties were shown to be associated with limbal epithelial stem cell (LESC) residence. Based on these findings, we then provided the first demonstration of the capacity to modulate LESC phenotype, both in vivo and ex vivo, solely through the recreation/restoration of suitable biomechanical niches. These results thus confirm the fundamental role of corneal biomechanics in directing epithelial stem cell behavior.


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