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snavely � pharmaceutical processing with supercritical carbon dioxide j pharm sci gokhale aa, nifedipine pregnancy risks khushi b, dave rn and pfeffer r formation of polymer nanoparticles in supercritical fluid jets nanotech may couvreur p polyalkylcyanoacrylates as colloidal drag carriers crit rev ther drug carr syst brannonpeppas l polymers in controlled drug delivery med plastics biomater mag kumar mnv nano and microparticles as controlled drug delivery devices } pharm pharmaceut nifedipine pregnancy risks sci mccarron pa, donnelly rf, canning pe, mcgovern jg and jones ds bioad hesive, nondrugloaded nanoparticles as modulators of candidal adherence to buccal epithelial cells a potentially novel prophylaxis for candidosis biomaterials chng hs, park h, kelly p and robinson jr bioadhesive polymers as platforms for oral controlled drug delivery ii synthesis and evaluation nifedipine pregnancy risks of some swelling, water insoluble bioadhesive polymers j pharm sci leung sr, j polymer structure features contributing to mucoadhesion ii j control rel sanzgiri y, topp e, benedetti l and stella v evaluation of mucoadhesive properties of hyaluronic acid benzyl esters int j pharm luessen hl, verhoef jc, borchard g, lehr cm, de boer ag and junginger he mucoadhesive polymers in peroral peptide drug delivery ii carbomer and polycar bophil are potent inhibitors of the intestinal proteolytic enzyme trypsin pharm res park kr, j bioadhesive polymers as platforms for oralcontrolled drug delivery method to study bioadhesion int} pharm nagai tm, y buccal delivery systems using hydrogels adv drug nifedipine pregnancy risks del rev taylan b, yilmaz c, guven o, kes s and hincal a design evaluation of sustained release and buccal adhesive propranolol hydrochloride tablets j control rel leung s and robinson j the contribution of anionic polymer structural features to mucoadhesion} control rel venugopalan p, sapre a, venkatesan n and vyas sp pelleted bioadhesive polymeric nanoparticles for buccal delivery of insulin preparation and characterization pharmazie gandhi r and robinson j bioadhesion in drug delivery indian j pharm sci neuberger w treatment of periodontal disease with photosensitizers, int patent wo a chowdhary rk and dolphin d supports for photosensitizer formulations, us patent no hejazi r and amiji m stomachspecific nifedipine pregnancy risks antih pylori therapy i preparation and characterization of tetracylineloaded chitosan microspheres int } pharm umamaheshwari rb, ramteke s and jain nk antihelicobacter pylori effect of mucoadhesive nanoparticles bearing amoxicillin in experimental gerbils model aaps pharmscitech ezpeleta i, arangoa ma, irache jm, stainmesse s, chabenat c, popineau y and orecchioni am preparation of ulex europaeus nifedipine pregnancy risks lectingliadin nanoparticle conjugates and their interaction with gastrointestinal mucus int} pharm dawson m, krauland e, wirtz d and hanes j transport of polymeric nanoparticle gene carriers in gastric mucus biotechnol prog gao h, wang jy, shen xz, deng yh and zhang w preparation of magnetic polybutylcyanoacrylate nanospheres encapsulated with aclacinomycin a and its effect nifedipine pregnancy risks on gastric tumor world j gastroenterol ponchel g and irache j specific and nonspecific bioadhesive particulate systems for oral delivery to the gastrointestinal tract adv drug del rev jani p, halbert gw, langridge j and florence at nanoparticle uptake by the rat gastrointestinal mucosa quantitation and particle size dependency i pharm pharmacol araujo l, nifedipine pregnancy risks sheppard m, lobenber rand kreuter j uptake of pmma nanoparticles from the gastrointestinal tract after oral administration to rats modification of the body distribution after suspension in surfactant solutions and in oil vehicles int pharm couvreur p, lenaerts v, kante b, roland m and speiser p oral and parentral administration of insulin associated hydrolysable nifedipine pregnancy risks nanoparticles acta pharm technol delie f and blancoprieto m polymeric particulates to improve oral bioavailability of peptide drugs molecules narayani r oral delivery of insulin � making needles needless trends biomater artif organs sakuma s, suzuki n, sudo r, hiwatari k, kishida a and akashi m optimized chemical structure of nanoparticles as carriers for nifedipine pregnancy risks oral delivery of salmon calcitonin int j pharm damge c, michel c, aprahamian m and couvreur p new approach for oral administration of insulin with polyalkylcyanoacrylate nanocapsules as drug carrier diabetes pan y, li yj, zhao hy, zheng jm, xu h, wei g, hao js and cui fd bioadhesive polysaccharide in protein delivery system nifedipine pregnancy risks chitosan nanoparticles improve the intestinal absorption of insulin in vivo int} pharm damge c, michel c, aprahamian m, couvreur p, devissaguet j nanocapsules as carriers for oral peptide delivery } control rel aboubakar m, couvreur p, pintoalphandary h, gouritin b, lacour b, farinotti r, puisieux f and vauthier � insulinloaded nanocapsules for oral administration nifedipine pregnancy risks in vitro and in vivo investigation drug dev res ramtoola z controlled release biodegradable nanoparticles containing insulin us patent no agnihotri sa, mallikarjuna nn and aminabhavi tm recent advances on chitosanbased micro and nanoparticles in drug delivery j control rel carino gp, jacob js and mathiowitz e nanosphere based oral insulin delivery j control nifedipine pregnancy risks rel foss ac, goto t, morishita m and peppas na development of acrylicbased copolymers for oral insulin delivery eur } pharm biopharm lee wk, park jy, yang eh, suh h, kim sh, chung ds, choi k, yang cw and park js investigation of the factors influencing the release rates of cyclosporin aloaded micro and nifedipine pregnancy risks nanoparticles prepared by highpressure homogenizer } control rel molpeceres l, aberturas mr and guzman m biodegradable nanoparticles as a delivery system for cyclosporine preparation and characterization j microencapsul elshabouri mh positively charged nanoparticles for improving the oral bioavailability of cyclosporina int} pharm young tj, johnston kp, pace gw and mishra ak phospholipidstablized nanoparticles of nifedipine pregnancy risks cyclosporine a by rapid expansion from supercritical to aqueous solution aaps pharmseitech wang xq, dai jd, chen z, zhang t, xia gm, nagai t and zhang q bioavailability and pharmacokinetics of cyclosporine aloaded phsensitive nanoparticles for oral administration j control rel varela mc, guzman m, molpeceres j, del rosario aberturas m, rodriguezpuyol d and rodriguezpuyol m cyclosporineloaded polycaprolactone nanoparticles immunosuppression and nephrotoxicity in rats eur j pharm sci cho m, levy r, pouletty p, floch r and merle � oral cyclosproin formulations, int patent wo chen j, yang wl, li g, qian j, xue jl, fu sk and lu dr transfection of mepo gene to intestinal epithelium in nifedipine pregnancy risks vivo mediated by oral delivery of chitosandna nanoparticles world j gastroenterol leong k, okoli g and hottelano g compositions for oral gene therapy and methods of using same international patent wo a chang sf, chang hy, tong yc, chen sh, hsaio fc, lu sc and liaw j nonionic polymeric micelles for oral gene delivery in vivo hum gene ther roy k, shauku h, sampsom h and leong � oral delivery of nucleic acid vaccines by particulate complexes us patent bl roy �, mao hq, huang sk and leong kw oral gene delivery with chitosan dna nanoparticles generates immunologic protection in a murine model of peanut allergy nat med nifedipine pregnancy risks kim sy, doh hj, jang mi i, ha yj, chung si and park hj oral immunization with helicobacter pyloriloaded polyd, llactidecoglycolide nanoparticles helicobacter pamujula s, graves ra, freeman t, srinivasan v, bostanian la, kishore v and �� m oral delivery of spray dried plgaamifostine nanoparticles} pharm pharmacol sharma a, sharma s and khuller gk nifedipine pregnancy risks lectinfunctionalized poly lactideco glycolide nanoparticles as oralaerosolized antitubercular drug carriers for treatment of tuberculosis} antimicrob chemother allison mc, cornwall s, poulter lw, dhillon ap and pounder re macrophage heterogeneity in normal colonic mucosa and in inflammatory bowel disease gut seldenrijk ca, drexhage ha and meuwissen sgm dendritic cells and scavanger macrophage in chronic inflammatory bowel disease gut probert cs, chott a, turner jr, saubermann lj, stevens ac, bodinaku k, elson co, balk sp and blumberg rs persistent clonal expansions of peripheral blood cd lymphocytes in chronic inflammatory bowel disease} immunol tabata y, inoue y and ikada y size effect on systemic and mucosal immune responses induced by oral nifedipine pregnancy risks administration of biodegradable microspheres vaccine lamprecht a, stallmach a, kawashima y and lehr cm carrier systems for the treatment of inflammatory bowel disease drugs put zhang h, alsarra ia and neau sh an in vitro evaluation of a chitosancontaining multiparticulate system for macromolecule delivery to the colon int j pharm rodriguez m, vilajato jl and torres d design of a new multiparticulate system for potential sitespecific and controlled drug delivery to the colonic region j control rel schmidt � and bodmeier r incorporation of polymeric nanoparticles into solid dosage forms j control rel refer to presentations and publications at wwwfdagovnanotechnology refer to the technical information posted by skye nifedipine pregnancy risks pharma at wwwskyepharmacom solubilizationhtml refer to the technical information posted by elan at http wwwelancomdrugde liverydrug deliverynanocrystaltechnologyasp arangoa ma, campanero ma, renedo mj, ponchel g and irache jm gliadin nanoparticles as carriers for the oral administration of lipophilic drugs relationships between bioadhesion and pharmacokinetics pharm res murakami hk, m takeuchi, h kawashima, y seroquel chat line utilization of polydllactide coglycolide nanaoparticles for preparation of mini depot tablets by direct compression j control rel tobio m, sanchez a, vila a, soriano ii, evora c, vilajato jl and alonso mj the role of peg on the stability in digestive fluids and in vivo fate of pegpla nanoparticles following oral administration coll surf � biointerf hillery a, florence a the effect of adsorbed poloxamer and surfactants on the intestinal uptake of nm polystyrene particles after oral administration in the rat int} pharm sakuma s, sudo r, suzuki n, kikuchi h, akashi m, ishida y and hayashi m behavior of mucoadhesive nanoparticles having hydrophilic polymeric chains in the intestine j control rel yoo hp, t biodegradable nanoparticles containing proteinfatty acid complexes for oral delivery of salmon calcitonin j pharm sci arbos p, campanero ma, arangoa ma and irache jm nanoparticles with specific bioadhesive properties to circumvent the presystemic degradation of fluorinated pyrimidines control rel jiao y, ubrich n, marchandarvier m, vigneron c, hoffman nifedipine pregnancy risks m, lecompte t and maincent p in vitro and in vivo evaluation of oral heparinloaded polymeric nanoparticles in rabbits circulation arbos p, campanero ma, arangoa ma, renedo mj and irache jm influence of the surface characteristics of pvmma nanoparticles on their bioadhesive properties j control rel barichello jm, morishita m, takayama � and nagai nifedipine pregnancy risks t encapsulation of hydrophilic and lipophilic drugs in plga nanoparticles by the nanoprecipitation method drug dev ind pharm molpeceres j, aberturas mr and guzman m biodegradable nanoparticles as a delivery system for cyclosporine preparation and characterization } microencapsul ubrich n, schmidt c, bodmeier r, hoffman m and maincent p oral evaluation in rabbits of nifedipine pregnancy risks cyclosporinloaded eudragit rs or rl nanoparticles int} pharm mesiha ms, sidhom mb and fasipe � oral and subcutaneous absorption of insulin polyisobutylcyanoacrylate nanoparticles int ] pharm pamujula s, graves ra, freeman t, srinivasan v, bostanian la, kishore v and mandal tk oral delivery of spray dried plgaamifostine nanoparticles j pharm pharmacol nanoparticular carriers for nifedipine pregnancy risks ocular drug delivery alejandro sanchez and maria j alonso the major goal in ocular drug delivery is to obtain therapeutic drug concentrations at the intended site of action ie located at the eye surface or in the inner eye, for reasonable periods of time the strategies explored towards this goal have been i the design of topical ocular delivery systems which promote the concentration of the drug on the eye surface, and, if necessary, facilitate the drug transfer from the extraocular tissues to the internal structures of the eye ii the design of injectable controlled release systems which deliver the drug directly to the sclera subconjunctival injection or nifedipine pregnancy risks to the internal structures of the eye intravitreal injection, for extended periods of time among the delivery systems designed so far for these purposes, those of a nanoscale size are particularly attractive from the point of view of easiness of administration and patient acceptability, since they can be applied in the form of a nonviscous liquid this chapter aims to describe the advances and the actual potential of polymerbased nanostructures such as nanoparticles and nanocapsules, for topical ocular drug delivery since the complexity of these nanostructures has increased over the time, these nanostructures have been classified into first, second and thirdgeneration nanocarriers additionally, the last sections of the nifedipine pregnancy risks chapter were intended to present the possibility to use nanoparticulate drug carriers for injection ie subconjunctival, intravitreal, and to underline the specific advantages of nanosystems over large dimensional devices for intraocular drug delivery overall, this review chapter shows the great potential that nanosystems offer in terms of improving the efficacy of drugs used in nifedipine pregnancy risks ocular therapies moreover, it emphasizes that the advances achieved in the understanding of the interaction of nanosystems with the ocular tissues should, logically, result in the design of sophisticated systems specifically tailored for ocular drug delivery biopharmaceutical barriers in ocular drug delivery classification of nanoparticulate carriers for ocular drug delivery unlike other routes described in previous chapters of this book, the different modalities of ocular administration ie topical, subconjuctival and intravitreal are exclusively intended to deliver drugs locally for the treatment of ophthalmic processes, and not as an entry to the systemic circulation among these modalities, the topical ocular administration is the easiest and best accepted by the nifedipine pregnancy risks patients liquid formulations, solutions and suspensions, are the most commonly applied for topical ocular administration, since they are easy to use and do not interfere with vision however, these formulations are often quite ineffective due to the defense mechanisms of the ocular apparatus these mechanisms have been described in detail in several review articles nifedipine pregnancy risks and textbooks firstly, most of the drug applied topically onto the eye is immediately diluted in the precorneal tear film the excess fluid spills over the lid margin and the remainder is rapidly drained into the nasolachry mal duct as a consequence, most of the applied drug solution is cleared within min in addition, a proportion of the drug will not be available for therapeutic action at the ocular level, but will be absorbed to the systemic circulation through the surrounding extraorbital tissues, mainly the conjunctiva unproductive drug absorption on the other hand, in the case of drugs whose target is located in the inner eye, they need to overcome the very important additional barrier represented by the cornea, which is the main entrance to the inner eye the area of contact of the drug with the cornea is restricted to approximately cm this small fraction of drug in contact with the cornea is then confronted with the very restrictive subbarriers such nifedipine pregnancy risks as the epithelium, the stroma and the endothelium both the first and the last barrier, but particularly the first, limit the absorption to water soluble substances, due to the existence of tight junctions between the epithelial cells the stroma, with high water content, limits the absorption of lipophylic drugs as a result of the above mentioned processes, typically less than of the instilled dose reaches the aqueous humour, this extremely low ocular bioavailability often implies the necessity of frequent dose administration, a situation that may lead to a significant systemic absorption and the corresponding side effects in some instances, the required posologic regimen is unviable and hence the nifedipine pregnancy risks intravitreal injection becomes necessary to achieve significant drug levels in the intraocular structures these biopharmaceutical constraints clearly evidence the necessity to conceive new ocular drug delivery strategies aimed at overcoming the above indicated barriers unfortunately, the requisite to preserve both the specific characteristics of the visual apparatus and the visual acuity, together with the nifedipine pregnancy risks inherent sensitivity of the eye, limit the possibilities of designing optimized ocular drug delivery systems substantially among the delivery strategies aimed at circumventing the above described limitations, the design of polymer nanoparticulate carriers offer unique features, while still benefit from their presentation in a liquid form two types of nanoparticulate carries have been described for ocular drug delivery matricetype nanoparticles, in which the biologically active molecule is entrapped or simply adsorbed onto their surface and reservoirtype nanocapsules, which consist of a polymeric wall surrounding a liquid drugcontaining core within the context of this chapter, the matricetype and the reservoirtype will be termed nanoparticles and nanocapsules respectively the fabrication processes of these nanostructures will not be a subject of description in this chapter, since they have already been reviewed despite the above indicated limitations in the design of ocular drug delivery systems, the efforts oriented towards the use of nanotechnologies have been relevant and they have led to significant progress in the field in this chapter, we review the advances made in the design of nanoparticulate carriers intended for topical ocular drug delivery these nanocarriers are classified into three categories first generation of basic nanoparticles and nanocapsules, second generation of nanoparticles and nanocapsules with a hydrophilic polymer coating, and the third generation of functionalized nanoparticles nanocapsules fig nifedipine pregnancy risks on the other hand, being conscious of the fact that the progress made in this field has not yet resulted in significant improvements in the therapy of innereye diseases, the potential of nanoparticles as injectable ocular drug delivery vehicles will also be described in this chapter indeed, polymer nanoparticles may circumvent the problem of nifedipine pregnancy risks frequent intravitreal injection by providing a controlled delivery of the encapsulated drug, thus reducing the clinical complications associated with this modality of administration nanoparticulate polymer compositions as topical ocular drug delivery systems as previously mentioned, the eye defense mechanisms represent the main limitation to the use of liquid formulations for ophthalmic therapy within this nifedipine pregnancy risks context, nanoparticles offer great possibilities of increasing the amount of drug at the anterior chamber of the eye, while spacing the dose administration table and table summarize the literature reports on the use of nanoparticulate polymer compositions as topical ocular drug delivery systems fig schematic representation of different nanosystems intended for ocular drug delivery first generation of basic matricetype nanoparticles the biologically active molecule is entrapped or simply adsorbed onto their surface and reservoirtype nanocapsules the biologically active molecule is dissolved in a liquid core surrounded by a polymeric wall second generation of nanoparticles and nanocapsules the figure shows a nanocapsule with a hydrophilic polymer coating and third nifedipine pregnancy risks generation of surface functionalized nanoparticlesnanocapsules the figure shows a nanocapsule functionalized with antibodies first generation polymer nanoparticles and nanocapsules for topical ocular drug delivery first generation polymer wall nanoparticle nanocapsule second generation coating approach third generation hydrophilic polymer coating functionalized nanocarriers targeting coating nanoparticles, primarily developed for iv administration, were first proposed for ophthalmic nifedipine pregnancy risks drug delivery in indeed, it was gurny and coworkers who first indicated the potential advantages of nanoparticles named pseudolatexes over aqueous polymer solutions more specifically, these authors found that pilocarpine adsorbed onto nanoparticles xm made of cellulose acetate phthalate cap were able to maintain a constant miosis in the rabbit for up to hours, nifedipine pregnancy risks compared with a hour response attained for pilocarpine eye drops this initial report was followed by a number of studies aimed at evaluating the potential of different types of polymers including acrylic polymers, and, especially, polyalkyl cyanoacry lates ����, polyesters, ie polyecaprolactone, and polysaccharides, such as hyaluronic acid and chitosan, for ocular drug delivery nifedipine pregnancy risks a summary of the results obtained with these different nanoparticulate formulations is presented in table table nanoparticulate compositions used in ocular drug delivery topical administration polymer typea drug in vivo resultsb references system type pilocarpine nanoparticles ibuprofen flurbiprofen nanoparticles cloricromene nanoparticles epinephrine nanoparticles hprogesterone nanoparticles pecl pilocarpine nanoparticles betaxolol nanoparticles amikacine nanoparticles hcyclosporin nanocapsules nifedipine pregnancy risks metipranolol nanocapsules betaxolol nanocapsules nanoparticles carteolol nanocapsules nanoparticles cyclosporin a nanocapsules indomethacin nanocapsules cap eudragit� pipaa ���� nanoparticles prolonged miosis improved ocular bioavailability aqueous humour drug levels and inhibition of the miosis induced by a surgical trauma improved ocular bioavailability aqueous humour drug levels prolonged iop lowering effect reduced drug concentrations in cornea, conjunctiva and aqueous humor prolonged miosis prolonged miosis and improved reduction of iop improved ocular bioavailability aqueous humour drug levels, prolonged miosis and improved reduction of iop for pilocarpineloaded nanoparticles prolonged intraocular pressure iop lowering effect improved ocular bioavailability corneal and aqueous humour drug levels prolonged therapeutic levels in cornea, sclera, uvea and retina as nifedipine pregnancy risks compared to those provided by an oily ciclosporin solution reduction of cardiovascular side effects and enhanced iop lowering effect enhanced iop lowering effect in a greater extent than ���� or plga effect more important for pecl nanocapsules than for nanoparticles improved iop lowering effect, being this effect superior for nanocapsules than for nanoparticles reduction of cardiovascular side effects for nanocapsules increased and more prolonged cyclosporin corneal levels as compared with those corresponding to an oily cyclosporin solution improved bioavailability eg cornea, aqueous humour and irisciliary body drug levels as compared with that of indomethacinloaded microparticles zm, and that of a control solution table continued polymer typea drugin vivo nifedipine pregnancy risks resultsb references system type chitosancyclosporin a higher and more prolonged cyclosporin levels at nanoparticles external ocular tissues eg cornea and conjunctiva and negligible intraocular and systemic levels, as compared with those corresponding to a cyclosporin suspension in a chitosan solution acap cellulose acetate phthalate pipaa polyisopropylacrylamide eudragits� copolymers of ethy lacrylate, methylmethacrylate and chlorotrimethylammonioethylmethacrylate nifedipine pregnancy risks pecl polyepsilon caprolactone pla poiyiactic acid ���� polyalquilcyanoacrylate biop intraocular pressure acrylic polymersbased nanoparticles the first study reporting the potential of polyacrylic nanoparticles for ocular drug delivery was published by wood et al more specifically, these authors found that ���� nanoparticles were significantly retained in the precorneal area, and therefore could act as nanoreservoires nifedipine pregnancy risks for extended drug delivery indeed, this improved retention of the carrier at the ocular surface was the explanation for the increased drug concentration in the cornea, and for the enhanced andor prolonged pharmacological effect reported for antiglaucoma drugs, such as pilocarpine, betaxolol and carteolol, the aminoglucoside amikacine and the immunosuppressive peptide cyclosporin a moreover, nifedipine pregnancy risks some authors found that the retention and residence time of nanoparticles was significantly increased in inflamed ocular tissues this was attributed to an enhanced epithelial permeability of the swollen conjunctival tissue there have also been examples for which the ocular bioavailability of the drug associated to ���� nanoparticles was reduced, compared with that of nifedipine pregnancy risks the free drug this negative result has been attributed to the great affinity of the drug progesterone for the polymer, and consequently, to its deficient delivery from the carrier unfortunately, despite the reported efficacy of ���� nanoparticles for enhancing the ocular bioavailability of drugs, the study reported by zimmer et al in evidenced that nifedipine pregnancy risks the nanoparticles entered the corneal epithelial cells, causing a disruption of cell membranes whether this negative result was due to specific experimental conditions of the reported study, or to the intrinsic nature of the ���� and its degradation products, remains to be clarified nevertheless, this could possibly provide the explanation for the little attention nifedipine pregnancy risks that ���� nanoparticles have attracted over the last decade, for this specific application interestingly, the toxicity reported for pacas has not dissuaded the research on the other types of acrylic polymers such as copolymers of ethylacrylate, methyl methacrylate and chlorotrimethylammonioethylmethacrylate eudragits� and polyacrylamide in the case of eudragit� nanoparticles, the in vivo results showed nifedipine pregnancy risks an enhanced bioavailability aqueous humour drug levels of the anti inflamatory drugs eg ibuprofen, flurbiprofen, as well as an improved pharmacological response on the other hand, using epinephrineloaded polyacrylamide nanoparticles, it was possible to prolong the intraocular pressure iop lowering effect caused by epinephrine while these studies underline the positive interaction of acrylic nanoparticles with the ocular mucosa, further studies in terms of tolerance and toxicity are required to assess the practical application of these nanoparticles polyesterbased nanoparticles and nanocapsules the results obtained for ���� nanoparticles stimulated the search for new nanoparticulate carriers made of different polymers within this context, polye caprolactone pecl and the copolymers of lactic nifedipine pregnancy risks and glycolic acid plga have received a great deal of attention the choice of these polymers was based on their broad history of safe use in humans as suture materials and implants moreover, at present, there is significant evidence of the adequate ocular tolerability of nanoparticles composed of these materials according to our knowledge, the first reports on the efficacy of polyester for topical ocular drug delivery were published in , marchalheussler et al compared the performance of nanoparticles made of ����, pecl and plga containing betaxolol as a model drug, with that of the commercial eye drops the results showed that under the experimental conditions assayed, all nanoparticulate nifedipine pregnancy risks systems yielded an improved pharmacological response ie intraocular pressure lowering effect, compared with an aqueous eye drop control formulation of the drug, with the optimum responses being ascribed to pecl nanocapsules in this case, the improved pharmacological effect was believed to be due to the agglomeration of these hydrophobic nanoparticles in the conjunctival sac, nifedipine pregnancy risks thus forming a depot from which the drug is slowly delivered to the precorneal area simultaneously to this work, we reported the efficacy of pecl nanocapsules consisting of an oily core and a pecl wall for the ocular delivery of metipra nolol the results of this study performed in rabbits led us to conclude nifedipine pregnancy risks that pecl nanocapsules were not only able to increase the pharmacological effect of this drug, but also able to reduce the cardiovascular side effects associated with its systemic absorption , this positive behavior suggested that the nanocapsules enhanced the drug transport across the cornea and reduced the systemic absorption through the conjunctiva in our attempt nifedipine pregnancy risks to elucidate the mechanism of the action of these nanocapsules, we labeled them with rhodamine � and followed their interaction with the rabbit cornea and conjunctiva by the use of confocal laser scanning microscopy the results of these ex vivo studies clearly evidenced that pecl nanocapsules were able to penetrate the corneal epithelial cells, nifedipine pregnancy risks and that they also exhibited a preference for the cornea vs the conjunctiva consequently, this differentiated interaction with both the epithelial surfaces could be taken as an adequate explanation for their reported ability to enhance corneal penetration and reduce systemic absorption more importantly, no evidence of membrane alteration or signs of toxicity were detected nifedipine pregnancy risks in this study with the intention of investigating the determinants of the interaction of these particles with the ocular mucosa, and thus of their performance as ocular drug carriers, we compared the efficacy of pecl nanoparticles and nanocapsules nm with that of pecl microparticles xm the results clearly evidenced that the nanoscale size was nifedipine pregnancy risks critical with regard to the ability of the particles to enhance the ocular bioavailability of indomethacin fig consequently, these results led us to hypothesize that nanoparticles have a greater ability than microparticles to interact with the corneal epithelium cells a similar conclusion was extracted recently for the interaction of the polyester particles with the conjunctival cells in specific, these authors found that the in vitro uptake of nanoparticles by primary cultured rabbit conjunctival epithelial cells was more important than that of the microparticles the positive results obtained for metipranolol and indomethacin encouraged us to test the performance of these nanosystems for the topical delivery of the [ control solution indocollyre ?