Multiple Roles of Chitosan in Mucosal Drug Delivery: An Updated Review

Chitosan (CS) is a linear polysaccharide obtained by the deacetylation of chitin, which, after cellulose, is the second biopolymer most abundant in nature, being the primary component of the exoskeleton of crustaceans and insects. Since joining the pharmaceutical field, in the early 1990s, CS attracted great interest, which has constantly increased over the years, due to its several beneficial and favorable features, including large availability, biocompatibility, biodegradability, non-toxicity, simplicity of chemical modifications, mucoadhesion and permeation enhancer power, joined to its capability of forming films, hydrogels and micro- and nanoparticles. Moreover, its cationic character, which renders it unique among biodegradable polymers, is responsible for the ability of CS to strongly interact with different types of molecules and for its intrinsic antimicrobial, anti-inflammatory and hemostatic activities. However, its pH-dependent solubility and susceptibility to ions presence may represent serious drawbacks and require suitable strategies to be overcome. Presently, CS and its derivatives are widely investigated for a great variety of pharmaceutical applications, particularly in drug delivery. Among the alternative routes to overcome the problems related to the classic oral drug administration, the mucosal route is becoming the favorite non-invasive delivery pathway. This review aims to provide an updated overview of the applications of CS and its derivatives in novel formulations intended for different methods of mucosal drug delivery.     

Acute corneal hydrops of presumed traumatic origin: An uncontrolled case series (three horses)

This case series describes acute corneal hydrops in three young horses. Due to similarities in the clinical appearance and progression of the disease with that which is reported in humans and cats with acute corneal hydrops, traumatic Descemet’s membrane rupture was suspected to be the underlying aetiology in these equine cases. The horses presented with acute severe corneal oedema with intrastromal bullae formation and anterior bulging of the corneal contour. Focal posterior corneal changes were also seen in two of three cases. Mild anterior uveitis was also present. Other causes of corneal oedema (e.g. glaucoma) were ruled out based on presentation and clinical examination. Treatment approaches were medical and included various combinations of prophylactic topical antimicrobial therapy in case of secondary corneal ulceration, anti-inflammatory therapy for uveitis, targeted oedema therapy with topical hypertonic saline and corneal cross-linking, and placement of a temporary partial tarsorrhaphy for corneal tamponade. The outcome was excellent in all cases, with rapid resolution of the ocular changes. Acute corneal hydrops of presumed traumatic Descemet’s membrane rupture origin should be considered in cases of young horses presenting with acute corneal oedema. However, further studies are warranted to better characterise the disease and to try to confirm the suspected aetiology.     

Canine ocular thelaziosis caused by Thelazia callipaeda in Portugal

Ocular thelaziosis caused by Thelazia callipaeda is a vector‐borne disease affecting dogs and humans. We report a case of thelaziosis in a 10‐year‐old German Shepherd dog from Vila Real city (Portugal). Ophthalmological examination revealed bulbar and nictitating membrane conjunctival hyperemia with serous discharge noted at the left medial canthus and blepharitis. Schirmer tear test value and intraocular pressure were within the reference ranges in both eyes, and biomicroscopy showed a transparent cornea without lesions or edema and no inflammatory reaction in the anterior chamber. No funduscopic alterations were detected by direct and indirect ophthalmoscopic examination. When testing the nasolacrimal patency, two white worms were observed on the caruncle conjunctival surface with undulating movements that increased with light intensity. In total, eight worms were collected and morphologically identified as T. callipaeda (seven mature females and one male). PCR amplification of a 689 sequence of partial cytochrome c oxidase subunit 1 target gene confirmed the nematodes were T. callipaeda, haplotype 1. The dog was treated with a single subcutaneous injection of ivermectin combined with additional topical application of ophthalmic fusidic acid drops and oral milbemycin oxime. One week after treatment, no worms were detected and the ocular clinical signs resolved. The most recent reports of canine thelaziosis in the Iberian Peninsula should alert local health authorities to the zoonotic potential of infestation with T. callipaeda, which should be included in the differential diagnosis of conjunctivitis in dogs and humans.     

Comparative ocular anatomy of the western lowland gorilla

OBJECTIVE: To examine the lowland gorilla (Gorilla gorilla gorilla) eye and determine similarities to and differences between the mountain gorilla (Gorilla gorilla beringei) and the human eye. In addition, we compare our findings of G. g. gorilla to previous reports on the eye of this subspecies. PROCEDURES: A 13-year-old deceased male lowland gorilla and a 34-year-old deceased female lowland gorilla were included in the study. Gross and microscopic examinations of the formalin-fixed right eyeball of each gorilla were carried out. RESULTS: Globe dimensions of G. g. gorilla were similar to G. g. beringei and to humans. The limbal conjunctival epithelium and the choroid were densely pigmented. However, the distribution of the conjunctival pigment ring was different to that of G. g. beringei and the melanocytes of the choroid were unusually round. There were deep crypts in the anterior border layer of the iris, and the epithelium of the pars plana was uniquely irregular. Vertical corneal diameter was observed to be equal or greater than horizontal diameter in G. g. gorilla, which is in contrast to humans and to previous findings for G. g. beringei. Corneal thickness was closer to that of humans than to G. g. beringei. Posterior lens capsule thickness was noticeably greater than that of humans. CONCLUSIONS: Although some variation between the ocular anatomy of G. g. gorilla and G. g. beringei does exist, the gross and microscopic findings closely resemble each other in these two subspecies. In addition, the eye of Gorilla appears remarkably similar to the human eye. However, comparison of measurements with those in humans is somewhat limited because formalin-fixation can introduce tissue shrinkage and artifact.     

Lymphosarcoma with conjunctival manifestation in a guinea pig

A guinea pig with multicentric lymphosarcoma and conjunctival manifestation is described. Primary clinical signs were bilateral infiltrative conjunctival masses. Antemortem diagnosis was based on the cytology of biopsies of conjunctival tissue, fine-needle aspirates of peripheral lymph nodes, and peripheral blood smears.     

Evaluation of the Perkins® handheld applanation tonometer in the measurement of intraocular pressure in dogs and cats

Objective  To evaluate and to validate the accuracy of the Perkins^® handheld applanation tonometer in the measurement of IOP in dogs and cats.
Animals  Twenty eyes from 10 dogs and 10 cats immediately after sacrifice were used for the postmortem study and 20 eyes from 10 clinically normal and anesthetized dogs and cats were used for the in vivo study. Both eyes of 20 conscious dogs and cats were also evaluated.
Procedure  Readings of IOP postmortem and in vivo were taken using manometry (measured with a mercury column manometer) and tonometry (measured with a Perkins^® handheld applanation tonometer). The IOP measurement with Perkins^® tonometer in anesthetized and conscious dogs and cats was accomplished by instillation of proxymetacaine 0.5% and of 1% fluorescein eye drops.
Results  The correlation coefficient ( r ²) between the manometry and the Perkins^® tonometer were 0.982 (dogs) and 0.988 (cats), and the corresponding linear regression equation were y  = 0.0893 x  + 0.1105 (dogs) and y  = 0.0899 x  + 0.1145 (cats) in the postmortem study. The mean IOP readings with the Perkins^® tonometer after calibration curve correction were 14.9 ± 1.6 mmHg (range 12.2–17.2 mmHg) in conscious dogs, and were 15.1 ± 1.7 mmHg (range 12.1–18.7 mmHg) in conscious cats.
Conclusion  There was an excellent correlation between the IOP values obtained from direct ocular manometry and the Perkins^® tonometer in dogs and cats. The Perkins^® handheld tonometer could be in the future a new alternative for the diagnosis of glaucoma in veterinary ophthalmology.     

ANTIMICROBIAL SUSCEPTIBILITY PATTERNS OF BIOFILM FORMING STAPHYLOCOCCUS AUREUS ISOLATED FROM PIGEON EXTERNAL OCULAR INFECTIONS

Pathogenic microorganisms are commonly associated with external ocular infections in birds. Pathogen virulence factors as well as reduced host defenses resulting from poor living conditions, nutrition, genetics, physiology, hygiene, fever, and age may increase host susceptibility. Staphylococcus species are bacteria known to serve as opportunistic pathogens in eye infections. The changing profile of microorganisms involved in ocular infections and the emergence of acquired microbial resistance dictate the need for investigative studies regarding bacterial profiles and antimicrobial susceptibility patterns for external ocular infections. The aim of this study was to determine the prevalence of Staphylococcus aureus ocular infections in pigeons and to evaluate their biofilm production ability and antibiotic resistance patterns. Twenty pigeons with confirmed eye infections were included in this project. Conjunctival specimens were collected with swabs presoaked in sterile normal saline. Bacterial growth was identified by standard laboratory procedures and susceptibility testing of the isolates was performed by the Kirby-Bauer method. The ability of the isolates to form a biofilm was also assessed using the microtiter plate method. Of the 20 specimens processed, 20% of the pigeons had staphylococcal eye infections. The resistance pattern of these isolates showed that Staphylococcus spp. from pigeon samples were resistant to tetracycline (100%), erythromycin (100%), azithromycin (100%), nalidixic acid (100%), and cefazolin (50%). All of the Staphylococcus spp. isolated from the pigeons were susceptible to gentamycin and furazolidone. The results of the biofilm detection test showed that 75% of the isolates were biofilm producers. In conclusion, biofilm forming S. aureus with multidrug resistance patterns were the most prevalent bacteria isolated from the pigeons examined in this research study.     

Successful use of topical mitomycin C for the treatment of a putative neoplastic vascular mass on the nictitating membrane of a dog

A nine-year-old female desexed Great Dane presented with a painful, proliferative, soft red putative neoplastic vascular mass on the nictitating membrane. Three 7-day cycles of the topical cytotoxic drug mitomycin C 0.04%, applied four times daily to the lesion using a low-dose alternate-week pulse therapy, brought about rapid remission of the lesion. The lesion was still in remission at time of euthanasia some 13 months later.