Prototyping Trastuzumab Docetaxel Immunoliposomes with a New FCM-Based Method to Quantify Optimal Antibody Density on Nanoparticles.

Developing targeted nanoparticles is a rising strategy to improve drug delivery in oncology. Antibodies are the most commonly used targeting agents. However, determination of their optimal number at the surface remains a challenging issue, mainly due to the difficulties in measuring precisely surface coating levels when prototyping nanoparticles. We developed an original quantitative assay to measure the exact number of coated antibodies per nanoparticle. Using flow cytometry optimized for submicron particle analysis and beads covered with known amounts of human IgG-kappa mimicking various amounts of antibodies, this new method was tested as part of the prototyping of docetaxel liposomes coated with trastuzumab against Her2+ breast cancer. This quantification method allowed to discriminate various batches of immunoliposomes depending on their trastuzumab density on nanoparticle surface (i.e., 330 (Immunoliposome-1), 480 (Immunoliposome-2) and 690 (Immunoliposome-3), p = 0.004, One-way ANOVA). Here we showed that optimal number of grafted antibodies on nanoparticles should be finely tuned and highest density of targeting agent is not necessarily associated with highest efficacy. Overall, this new method should help to better prototype third generation nanoparticles.

[Congenital anophthalmos. Control of osteogenesis with an expanding intraorbital prosthesis]. / Anophtalmie congénitale. Contrôle de l'ostéogenèse par prothèse expansive intraorbitaire.

Both congenital anophthalmia and severe microphthalmia lead to micro-orbit with early appearance of craniofacial hemiatrophy. There is simultaneous lack of development of the lids (which remain small but complete) and of the conjunctival sac. Use of esthetic ocular prosthesis is thus impossible. The conjunctival sac can be dilated with conformators of increasing size but this technique has no effect on the orbit. The results of repeated plastic surgery are unsatisfactory. Stimulation of ocular growth by an expandable prosthesis in early infancy would appear to be the most logical and effective therapy. The authors propose a "new" technique for the expansion of the orbital cavity of the congenital anophthalmia. They have deviced a silicone prosthesis which is progressively expanded in size. The device has now been in use for over eighteen months with really encouraging results (17 cases).

[The chondromucosal graft. Its use in the correction of entropion caused by tarsoconjunctival cicatrix, trichiasis and distichiasis]. / La greffe chondro-muqueuse. Son intéret dans la correction de l'entropion par cicatrice tarso-conjonctivale, du trichiasis et du distichiasis.

The use of chondromucosal grafts is the classical treatment for reconstruction of the eyelids, whereas these grafts are less employed for correction of tarso-conjunctival scars due to either disease or surgery. The ideal nasal graft is the triangular cartilage, as its mucosa is more delicate and more adhesive than that of the septum, and it separation and positioning do not involve any problems if certain rules are followed. The technique appears attractive to us, as it is simple to perform, there is a lack of postoperative complications and it is logical (replacing a pathological tissue or a missing tissue by an identical one, keeping the lids framework). It appears to be not enough employed in trachomatous entropion (both eyelids being generally affected). However, the technique is useful: during first intention surgery (whether associated or not with tarsectomy); in all cases of recurrence, where it appears to be the only worthwhile treatment (trachomatous eyelids already operated upon by another method, tarsectomy alone).

[Conjunctival sac of anophthalmic orbits]. / Le sac conjonctival de l'orbite anophtalme.

Reconstruction of the conjunctival sac is never a simple procedure. It is a question of positioning a prosthesis in the orbital cavity which will have no anatomic support, as the eye has been enucleated, reduced to a stump (microphthalmos) or has been replaced by an implant that has just been expelled. All described techniques consist in enlarging the existing conjunctival sac, and then positioning a mucosal or dermo-epidermical graft in the orbital cavity maintained by a conformer. In order to limit the effects of the inevitable retraction during the first weeks following surgery, operative enlargement beyond the needs of the conjunctival sac is essential. The conformer should be supported by tarsorraphy until the phenomenon of retraction has reached an end (4 to 6 months). The problem of the "orbital cavity" must be understood so that indications for surgical remodelling of the conjunctival sac can be established. This is simple after enucleation, but more complex in the case of a microphthalmos, an injury, or an exenteration of the orbit where remodelling represents only the last operative stage after bone remodelling, or lids remodelling and sometimes transposition of the temporalis muscle in the socket.

[Eyelid burns]. / La paupière du brûlé.

Reconstruction of eyelids following burns has two fold objective: functional and esthetic. Except in the must severe forms (carbonization) eyelids' burns usually involve only superficial lesions. Surgery, by means of a skin graft only, may be required after initial medical treatment. The choice of a graft among those considered standard, (full-thickness skin graft for the lower lid, thinner graft for the upper lid) should be guided by anatomophysiological considerations. Treatment in each case varies according to the anatomic type and the stage of evolution of the burn; whether the orbicularis muscle has been affected or not, should determine the choice of the graft. Certain points of this surgical technique have to be emphasized: the need for respecting esthetic unity; for careful dissection sparing the orbicularis; for fixation of the graft on the medial canthus, and lastly, the necessity of performing surgery of upper and lower lids in two stages so that the lid is "in surocclusion" during each operative procedure. Treatment of eyelids' burns as described above, is well established. It is very different from that for total facial burns, which requires total operative strategy.

Computed tomography of the optic nerve: part II. Size and shape modifications in papilledema.

Increase in the caliber and course tortuosity of the optic nerve (ON) can be demonstrated by computed tomography (CT) in cases of papilledema due to intracranial tumors, hydrocephalus, pseudotumor cerebri, and other conditions causing increased intracranial pressure. The enlargement of the ON in these conditions is generally bilateral, although one of the nerves, usually of the side of the tumoral pathology, may be thicker. Enlargement on the ON may also be demonstrated by CT in papilledema due to optic neuritis. Occasionally, the thickened ON also display increased attenuation coefficient values.