Cellular-level Studies Research Articles

Vesicular carriers containing phenylethyl resorcinol for topical delivery system; liposomes, transfersomes and invasomes

Topical administration of phenylethyl resorcinol (PR) has attracted much attention as skin lightening agent with potent anti-tyrosinase activity. Two novel types of elastic carriers were developed to overcome the limitation of PR as topical delivery by increasing the solubility, stability and decreasing skin irritation compared to conventional liposomes. In addition, it also promotes skin penetration of PR to reach deep skin layer at the target site. The lead formulations were obtained from the invasomes containing 1% (w/v) d-limonene mixed with 10% (v/v) absolute ethanol as the skin enhancer, and transfersomes containing 15% (w/w) sodium deoxycholate (SDC) as edge activator. All formulations gave a vesicle size < 500 nm, polydispersity index (PDI) < 0.3, high zeta potential, entrapment efficiency > 50%, and good stability on storage at 30 °C at 75% RH for 4 months. Transfersomes have a lower degree of deformability (6.63%) than invasomes (25.26%). In contrast, the liposomes as rigid vesicles do not show a deformable property. This characteristic affects the skin permeation, and thus, transfersomes with high elastic property provided a significantly higher cumulative amount, steady state flux (Jss) and permeability coefficient (Kp) compared to other formulations. However, in vitro PR accumulation in full-thickness newborn pig skin demonstrated that the application of elastic carrier formulations gave significantly higher accumulation than liposomes, and gave anti-tyrosinase activity up to 80%. These results are straightforwardly related to the results of cellular level study. Transfersomes and invasomes showed higher tyrosinase inhibition activity and melanin content reduction when compared to liposomes in B16 melanoma cells. In addition, acute irritation test in rabbits confirmed that these formulations are safe for skin application. Therefore, elastic vesicle carriers have the efficiency to deliver PR into the deep skin in both quantity and effectiveness which are better than conventional liposomes and appropriate for a skin lightening product.

Neurobiological bases of autism-epilepsy comorbidity: a focus on excitation/inhibition imbalance.

Autism spectrum disorders (ASD) and epilepsy are common neurological diseases of childhood, with an estimated incidence of approximately 0.5-1% of the worldwide population. Several genetic, neuroimaging and neuropathological studies clearly showed that both ASD and epilepsy have developmental origins and a substantial degree of heritability. Most importantly, ASD and epilepsy frequently coexist in the same individual, suggesting a common neurodevelopmental basis for these disorders. Genome-wide association studies recently allowed for the identification of a substantial number of genes involved in ASD and epilepsy, some of which are mutated in syndromes presenting both ASD and epilepsy clinical features. At the cellular level, both preclinical and clinical studies indicate that the different genetic causes of ASD and epilepsy may converge to perturb the excitation/inhibition (E/I) balance, due to the dysfunction of excitatory and inhibitory circuits in various brain regions. Metabolic and immune dysfunctions, as well as environmental causes also contribute to ASD pathogenesis. Thus, an E/I imbalance resulting from neurodevelopmental deficits of multiple origins might represent a common pathogenic mechanism for both diseases. Here, we will review the most significant studies supporting these hypotheses. A deeper understanding of the molecular and cellular determinants of autism-epilepsy comorbidity will pave the way to the development of novel therapeutic strategies.

Response of plasma glucagon-like peptide-2 to feeding pattern and intraruminal administration of volatile fatty acids in sheep

Glucagon-like peptide-2 (GLP-2), a gut peptide secreted by enteroendocrine L cells, has recently been identified as a key regulator of intestinal growth and absorptive function in ruminants. However, reports on GLP-2 secretion are few, and more information regarding its secretion dynamics is needed. In this study, two experiments were conducted to elucidate the daily rhythm of GLP-2 secretion in response to feeding regimen and to investigate the effect of volatile fatty acids (VFA) on GLP-2 release in sheep. In experiment 1, blood samples were collected over 3 d from 4 Suffolk mature wethers adapted to a maintenance diet fed once daily; day 1 sampling was preceded by 24 h of fasting to reach steady state. On days 1 and 3, samples were collected every 10 min from 11:00 to 14:00 on both days and then every 1 h until 00:00 on day 1 only; feed was offered at 12:00. On day 2, feed was withheld, and sampling was performed every hour from 01:00 to 00:00. In experiment 2, 5 Suffolk mature wethers were assigned to 5 treatment groups of intraruminal administration of saline, acetate, propionate, butyrate, or VFA mix (acetate, propionate, and butyrate in a ratio of 65:20:15) in a 5 × 5 Latin square design. Blood samples were collected at 0, 1.5, 3, 6, 9, 12, 15, 20, 25, 30, 40, 50, 60, 90, and 120 min relative to the beginning of administration at 12:00. In both experiments, plasma GLP-2, glucagon-like peptide-1 (GLP-1), glucose, insulin, and β-hydroxy butyric acid (BHBA) levels were measured. In experiment 1, incremental area under the curve was greater (P < 0.05) post-feeding than pre-feeding on days 1 and 3 for GLP-2 and tended to be greater (P < 0.1) on day 1 for GLP-1. Plasma insulin, glucose, and BHBA levels increased (P < 0.05) on day 1 post-feeding. Plasma GLP-2 was poorly correlated with GLP-1 but positively correlated with insulin, glucose, and BHBA. In experiment 2, administration of butyrate and VFA mix remarkably increased plasma GLP-2 (P = 0.05) and BHBA (P < 0.0001) levels compared with those in other treatments. Plasma GLP-1 levels were higher with butyrate administration compared with those in the saline, acetate, and VFA mix (P = 0.019). Propionate administration increased plasma glucose (P = 0.013) and insulin (P = 0.053) levels. Thus, our data confirmed that GLP-2 release is responsive to feeding and might be promoted by BHBA produced by the rumen epithelial metabolism of butyrate. Further molecular- and cellular-level studies are needed to determine the role of butyrate as a signaling molecule for GLP-2 release.

Ionizing radiation induced cataracts: Recent biological and mechanistic developments and perspectives for future research.

The lens of the eye has long been considered as a radiosensitive tissue, but recent research has suggested that the radiosensitivity is even greater than previously thought. The 2012 recommendation of the International Commission on Radiological Protection (ICRP) to substantially reduce the annual occupational equivalent dose limit for the ocular lens has now been adopted in the European Union and is under consideration around the rest of the world. However, ICRP clearly states that the recommendations are chiefly based on epidemiological evidence because there are a very small number of studies that provide explicit biological, mechanistic evidence at doses <2Gy. This paper aims to present a review of recently published information on the biological and mechanistic aspects of cataracts induced by exposure to ionizing radiation (IR). The data were compiled by assessing the pertinent literature in several distinct areas which contribute to the understanding of IR induced cataracts, information regarding lens biology and general processes of cataractogenesis. Results from cellular and tissue level studies and animal models, and relevant human studies, were examined. The main focus was the biological effects of low linear energy transfer IR, but dosimetry issues and a number of other confounding factors were also considered. The results of this review clearly highlight a number of gaps in current knowledge. Overall, while there have been a number of recent advances in understanding, it remains unknown exactly how IR exposure contributes to opacification. A fuller understanding of how exposure to relatively low doses of IR promotes induction and/or progression of IR-induced cataracts will have important implications for prevention and treatment of this disease, as well as for the field of radiation protection.

1P1-L09 がん細胞の遊走観察のためのグルコース・酸素濃度勾配生成マイクロ流路デバイス

Cancer cells inside tumors are under low glucose and oxygen concentration, which increase the migration capability and are assumed to be an origin of cancer metastasis. However, the cellular level studies of cancer cells inside tumors are difficult due to the limitation of the conventional biological approaches, which cannot generate the conditions inside tumors. In order to overcome the difficulty, we design and fabricate a microfluidic device that can control the glucose and oxygen concentrations inside a micro chamber. We achieved the concentration gradients similar to the gradient inside a tumor.

Quantitative Phase Imaging Techniques for the Study of Cell Pathophysiology: From Principles to Applications

A cellular-level study of the pathophysiology is crucial for understanding the mechanisms behind human diseases. Recent advances in quantitative phase imaging (QPI) techniques show promises for the cellular-level understanding of the pathophysiology of diseases. To provide important insight on how the QPI techniques potentially improve the study of cell pathophysiology, here we present the principles of QPI and highlight some of the recent applications of QPI ranging from cell homeostasis to infectious diseases and cancer.

Toxicological Evaluations of Rare Earths and Their Health Impacts to Workers: A Literature Review

In concert with the development of new materials in the last decade, the need for toxicological studies of these materials has been increasing. These new materials include a group of rare earths (RE). The use of RE nanotechnology is being considered in some green applications, to increase their efficiency by using nano-sized RE compounds, and therefore hazard evaluation and risk assessment are highly recommended. This review was conducted through an extensive contemplation of the literatures in toxicology with in vitro and in vivo studies. Major aspects reviewed were the toxicological evaluations of these elements and metallic compounds at the molecular and cellular level, animal and human epidemiological studies and environmental and occupational health impacts on workers. We also discuss the future prospect of industries with appliances using RE together with the significance of preventive efforts for workers' health. To establish a safe and healthy working environment for RE industries, the use of biomarkers is increasing to provide sustainable measure, due to demand for information about the health risks from unfavorable exposures. Given the recent toxicological results on the exposure of cells, animals and workers to RE compounds, it is important to review the toxicological studies to improve the current understanding of the RE compounds in the field of occupational health. This will help to establish a sustainable, safe and healthy working environment for RE industries.

ISOLATION, PURIFICATION and CHARACTERIZATION OF ACTIVE COMPOUND FROM ANDROGRAPHIS PANICULATA.L AND TESTING ITS ANTI-VENOM AND CYTOTOXIC ACTIVITY BY IN-VITRO and IN-VIVO STUDIES

Snake bite is a serious problem in tropical and subtropical countries like India with 5 mil lion human fatalities annually. The present study aimed on the shade grown Andrographis p aniculata L under organic condition. 6 month old plants were collected at dawn; shade dried and extracted with methanol, followed by fractionation to isolate the activ e compound and characterization of the active compound was done using FT - IR study which was found to be identified as andrographolide. Furthermore, in vivo and in vitro studies confirm the anti - venom property of the plant and the cytotoxic levels determin ed by the use of cell lines has its major start tow ards the cellular level study. These studies and investigations confirms the presence of cobra venom inhibiting factor whose bite pose a huge threat to the life of people. Commercializing the drug again st envenomation would prove successful in rural areas and the areas where the health centre is out of reach. Under economic circumstances, this study has the advantage of being very niggardly charged for the anti - venom preparation unlike the present day anti - venom that involves in rearing a horse and collecting the horse plasma that possess the raised anti - bodies which by further purification process would result in ASVS. Thus prepared ASVS holds the main disadvantage of bringing cross reactions like anaphyl axis and many more of the same sort. So, the plant as a drug would prove more effective, with high degree of safety and cost effective.

Effects of steroid hormones on differentiated glandular epithelial and stromal cells in a three dimensional cell culture model of the canine endometrium

BackgroundOestrogens and progesterone have a significant impact on the endometrium during the canine oestrous cycle. Their receptors mediate plasma steroid hormone levels and are expressed in several endometrial cell types. Altered steroid receptor expression patterns are involved in serious uterine diseases; however the mechanisms of hormone action during pathogenesis in these tissues remain unclear. The development of 3D culture systems of canine endometrial cells provides an opportunity for the effects of steroid hormones to be quantitatively assessed in a more in vivo-like setting. The present study aimed to determine the effects of the steroid hormones 17β-estradiol (E) and progesterone (P) on the expression of the oestrogen and progesterone receptors (ER and PR), and on proliferative activity, in a 3D co-culture system of canine uterine origin, comprising differentiated endometrial glands, and stromal cells (SCs).ResultsMorphology, differentiation, and apical-basolateral polarity of cultured glandular epithelial cells (GECs) were comparable to those in native uterine tissue as assessed by immunohistochemistry using differentiation markers (β-catenin, laminin), lectin histochemistry, and transmission electron microscopy. Supplementation of our 3D-culture system with E (at 15, 30 and 100 pg/mL) resulted in constant levels of ER expression in GECs, but reduced expression levels in SCs. PR expression was reduced in both GECs and SCs following treatment with E. 3 ng/mL P resulted in increased ER expression in GECs, but a decrease in SCs. PR expression in GECs increased in all P-treated groups, whereas PRs in SCs decreased with the lowest and highest doses, but increased with the middle dose of treatment. Proliferative activity, assessed by Ki67 staining, remained below 1% in all assays and cell types.ConclusionsThe present study demonstrates the applicability of our 3D organotypic canine endometrium-derived culture system for cellular-level studies. 3D cultures represent near-physiological systems allowing reproducible quantitative experimentation, thus reducing the need to experiment on living animals. The results of the present investigation emphasize the importance of co-culture of the uterine glands with SCs, as it was shown that the responsiveness of the different cell types to steroid hormones were divergent in the 3D cell culture model.

Proteomic and Electron Microscopy Survey of Large Assemblies in Macrophage Cytoplasm

Many cellular processes are carried out by large macromolecular assemblies. We systematically analyzed large macromolecular assemblies in the cytoplasm of mouse macrophages (RAW264.7 cell line), cells with crucial roles in immunity and inflammation. Fractionation of the cytoplasmic fraction was performed using sucrose density gradient centrifugation, and individual fractions were subjected in parallel to (i) identification of constituent proteins by mass spectrometry and (ii) structural visualization by electron microscopy. Macromolecular assemblies present in the fractions were analyzed by integrating available data using bioinformatic approaches. We identified 368 unique proteins in our sample. Among these are components of some well-characterized assemblies involved in diverse cellular processes and structures including translation, proteolysis, protein folding, metabolism, and the cytoskeleton, as well as less characterized proteins that may correspond to additional components of known assemblies or other homo- or hetero-oligomeric structures. Single-particle analysis of electron micrographs of negatively stained samples allowed the identification of clearly distinguishable two-dimensional projections of discrete protein assemblies. Among these, we can identify small ribosomal subunits and preribosomal particles, the 26S proteasome complex and small ringlike structures resembling the molecular chaperone complexes. In addition, a broad range of discrete and different complexes were seen at size ranges between 11 to 38 nm in diameter. Our procedure selects the assemblies on the basis of abundance and ease of isolation, and therefore provides an immediately useful starting point for further study of structure and function of large assemblies. Our results will also contribute toward building a molecular cell atlas.

Molecular Biomechanics: The Molecular Basis of How Forces Regulate Cellular Function

Recent advances have led to the emergence of molecular biomechanics as an essential element of modern biology. These efforts focus on theoretical and experimental studies of the mechanics of proteins and nucleic acids, and the understanding of the molecular mechanisms of stress transmission, mechanosensing and mechanotransduction in living cells. In particular, single-molecule biomechanics studies of proteins and DNA, and mechanochemical coupling in biomolecular motors have demonstrated the critical importance of molecular mechanics as a new frontier in bioengineering and life sciences. To stimulate a more systematic study of the basic issues in molecular biomechanics, and attract a broader range of researchers to enter this emerging field, here we discuss its significance and relevance, describe the important issues to be addressed and the most critical questions to be answered, summarize both experimental and theoretical/computational challenges, and identify some short-term and long-term goals for the field. The needs to train young researchers in molecular biomechanics with a broader knowledge base, and to bridge and integrate molecular, subcellular and cellular level studies of biomechanics are articulated.

Risks Associated with Low Doses and Low Dose Rates of Ionizing Radiation: Why Linearity May Be (Almost) the Best We Can Do

Deterministic and stochastic effects associated with high-dose ionizing radiation (x-ray) exposure have been known for almost as long as ionizing radiation itself (1–3). At lower doses, radiation risks are primarily stochastic effects, in particular, somatic effects (cancer) rather than the deterministic effects characteristic of higher-dose exposure (4–6). In contrast to deterministic effects, for stochastic effects, scientific committees generally assume that at sufficiently low doses there is a positive linear component to the dose response—that is, that there is no threshold (4–6). This does not preclude there being higher-order (eg, quadratic) powers of dose in the dose response that may be of importance at higher doses. It is on this basis that models linear (or linear-quadratic) in dose are often used to extrapolate the experience of the Japanese atomic bomb survivors (who were typically exposed at a high dose rate to moderate doses [average, 0.1 Sv]) to estimate risks from low doses and low dose rates (4–6). Most population-based cancer risk estimates are based primarily on the Japanese atomic bomb survivor Life Span Study (LSS) cohort data (4–6). However, evidence of excess risks comes from a large number of other studies as well. In the parallel editorial (7), evidence is presented for possible real (or at least “practical”) thresholds or “hormetic” (beneficial) effects of low doses of ionizing radiation. As we summarize here, and in contrast to the arguments of Tubiana et al (7), we judge that there is little epidemiologic or biologic evidence for these for cancer. The arguments are of three forms: (a) assessment of the degree of curvature in the cancer dose response within the Japanese atomic bomb survivors and other exposed groups (in particular, departure from linear or linear-quadratic curvature), (b) consistency of risks between the Japanese and other moderate- and low-dose cohorts, and (c) assessment of biologic data on mechanisms. Most of the information on radiation-induced cancer risk comes from (a) the Japanese atomic bomb survivors, (b) medically exposed populations, (c) occupationally exposed groups, and (d) environmentally exposed groups (6). In the higher-dose radiation therapy studies, where doses received are very much higher than in the LSS, sometimes in the range at which cell sterilization occurs, excess cancer risks per unit dose tend to be less than in comparable subsets of the LSS (8,9). However, as we show, risks in moderate- and low-dose medically and occupationally exposed groups are generally consistent with those in the LSS.

Cellular Level Biocompatibility and Biosafety of ZnO Nanowires

We report the first cellular level study on the biocompatibility and biosafety of ZnO nanowires (NWs). Hela cell line showed a complete biocompatibility to ZnO nanostructures from low to high NW concentrations beyond a couple of production periods. The L929 cell line showed a good reproduction behavior at lower NW concentration, but when the concentration was close to 100 μg/ml, the viability dropped to ∼50%. Our study shows the biocompetability and biosafety of ZnO NWs when they are applied in biological applications at normal concentration range.

Role of cortical cell type and neuronal morphology in electric field stimulation

Clinical application of transcranial magnetic stimulation (TMS) and transcranial current stimulation (TCS, encompassing transcranial direct current stimulation, cranial electrotherapy stimulation, transcranial electric stimulation, and electroconvulsive therapy) are promising non-invasive approaches for the treatment of a number of psychiatric disorders and pain. The cortex is the most common target of these non-invasive brain stimulation modalities. Cellular level studies of the electric fields, imposed by these brain stimulation modalities, state that cellular morphology predict the induced transmembrane polarization along a neuron.

Mechanisms of Arterial Remodeling in Hypertension

Diverse data collected over the past 4 decades suggest the existence of a mechanical homeostasis across multiple length and time scales in the vasculature. For example,1 stress fibers within endothelial and vascular smooth muscle cells appear to disassemble and then reassemble in a mechanically preferred manner when perturbed from a normal value of mechanical stress or strain; focal adhesions in smooth muscle cells and fibroblasts tend to increase in area in response to local increases in mechanical loading so as to maintain the stress constant at a preferred value; fibroblasts tend to increase the tractions that they exert on the extracellular matrix when external loads are decreased from a preferred value, thus suggesting an attempt to enforce a “tensional homeostasis”; vascular smooth muscle cells tend to relengthen to their normal, preferred values when an arteriole is forced into a vasoconstricted state for an extended period; and arteries tend to decrease in caliber in response to sustained decreases in flow-induced wall shear stress, to increase in thickness in response to sustained increases in pressure-induced circumferential stress, and to lengthen in response to extension-induced increases in axial stress. Although changes in the cytoskeleton and integrins occur within minutes, changes at the cell-cell and cell-matrix levels occur over hours, and those at the vessel level occur over days to weeks or months. Hence, despite marked differences in length scales (dimensions from nanometers to centimeters) and time scales (durations from minutes to months), mechanobiological control mechanisms in the vasculature tend to restore values of stress or strain toward preferred (homeostatic) values in response to diverse perturbations from normal.2–5 Biomechanics and mechanobiology thus play key roles in vascular development, tissue maintenance in maturity, normal adaptations, aging, disease progression, and responses to injury or clinical interventions. A current challenge in hypertension research is to …

Central nervous system projections to and from the commissural ganglion of the crab Cancer borealis

Higher-order inputs provide important regulatory control to motor circuits, but few cellular-level studies of such inputs have been performed. To begin studying higher-order neurons in an accessible model system, we have localized, in the supraesophageal ganglion (brain), neurons that are candidates for influencing the well-characterized motor circuits in the stomatogastric nervous system (STNS) of the crab Cancer borealis. The STNS is an extension of the central nervous system and includes four ganglia, within which are a set of motor circuits that regulate the ingestion and processing of food. These motor circuits are locally regulated by a set of modulatory neurons, most of which are located in the paired commissural ganglia (CoGs). These modulatory neurons are well-positioned to receive input from brain neurons because the circumesophageal commissures (CoCs) connect the brain with the CoGs. We have performed a series of CoC backfills to localize the brain neurons that are likely to innervate the CoGs and are, therefore, candidates for influencing the STNS motor patterns. CoC backfill-labeled neuronal somata within the brain are clustered around a subset of anatomically defined neuropil regions. We have concomitantly localized many CoG neurons that project into the brain. This latter pathway presumably includes neurons that provide feedback regarding ongoing STNS activity. Interestingly, nearly all of these brain and CoG neurons project through the medial aspect of the CoC. This work provides an initial framework for future studies to determine the way that higher-order input regulates rhythmic motor patterns.

RNA interference: An Ancient Mechanism for Novel Therapeutics

The siRNA approach for gene silencing holds great therapeutic promise, since siRNAs, like miRNAs, are naturally used by cells to regulate gene expression and hence are expected to be nontoxic and highly effective. Their therapeutic potential can be exploited maximally only when the mechanism underlying their localized and systemic activity is fully understood. Lower eukaryotes provide good model systems yet species specificity leading to minor differences at mechanistic level, point to their being investigated in mammalian milleu. In vitro cellular level studies have proven the therapeutic potential of iRNA to a larger extent. At present only one topical drug Vitravene targeting AMD is in market and several other RNAi based drugs are in the pipeline.

The effects of atorvastatin on gluten-induced intestinal T cell responses in coeliac disease

Various experimental models suggest that the cholesterol-lowering drugs statins may also modulate immune responses. Cellular level studies on human disorders are needed, however, to provide a rational basis for clinical testing of statins as immune therapy. Coeliac disease, a chronic small intestinal inflammation driven by HLA-DQ2 restricted mucosal T cells that are specific for ingested wheat gluten peptides, is in many ways ideal for this purpose. In addition, there is a need for alternative treatment to the gluten-free diet in this disorder. Here we have assessed the effects of atorvastatin on gluten-reactive T cells, dendritic cells and the coeliac mucosa by in vitro culture of biopsies. Atorvastatin inhibited gluten-induced proliferation and specific cytokine production of human intestinal gluten-reactive T cell clones and lines. Dendritic cells exposed to atorvastatin displayed a reduced expression of the costimulatory molecule CD83 upon maturation with lipopolysaccharide. Incubation of intestinal biopsy specimens with atorvastatin in vitro, however, did not influence gluten-induced cytokine release. In conclusion, atorvastatin has specific effects on isolated gluten-reactive T cells and dendritic cells, but does not shut down the gluten-induced production of proinflammatory cytokines in intestinal biopsies.

Biomechanics of Growth, Remodeling, and Morphogenesis

This review deals with biomechanical aspects of growth (mass change), remodeling (property change), and morphogenesis (shape change) in living systems. The emphasis is on theoretical models, but relevant experimental results also are discussed. As an aid to the reader, the fundamental biological terms and concepts are defined for the general problem and for each specific topic. At the outset, the processes involved in growth, remodeling, and morphogenesis are described and placed within the context of the evolution of species. Next, some of the analytical methods used in biomechanical models for these processes are presented. Then, applications of these and other techniques to specific systems are discussed, beginning at the cellular level and proceeding upward to the tissue and organ levels. At the cellular level, modeling and experimental studies are reviewed for cell division, cell movement, and pattern formation, and then morphogenetic mechanisms for epithelia (cell sheets) are discussed. At the tissue and organ levels, the musculoskeletal and cardiovascular systems are considered. Several models are described for growth, remodeling, and morphogenesis of bone, and mainly experimental results are examined in the cases of skeletal muscle, the heart, and arteries. Specific topics for the cardiovascular system include hypertrophy, residual stress, atherosclerosis, and embryonic development. Finally, some future research directions are suggested.

Bioadhesive, collagen-modified liposomes: molecular and cellular level studies on the kinetics of drug release and on binding to cell monolayers

Liposomes, modified by covalently-anchoring collagen to their surface, were investigated for their abilities to be bioadhesive and to act as sustained-release drug carriers. These bioadhesive liposomes have the potential to induce significant improvements in topical and regional therapies. The major findings for uni- (ULV) and multilamellar (MLV) bioadhesive liposomes are: (a) Both ULV and MLV release small molecular weight drugs over prolonged periods. For example, rate constants of ( 6 ± 0.5) · 10 −3 and ( 2.6 ± 0.8) · 10 −3 h −1, were obtained for the release of vinblastine and fluconazole, respectively, from collagen-ULV. (b) For a given drug, that rate constant can be shifted (up or down) by the choice of liposome type and collagen-surface density and the latter, if high enough, lead to the formation of an additional liposome-associated drug reservoir. (c) Using monolayers of the A431 cell line to model the in vivo targets, the bioadhesive (but not the regular) liposomes were found to bind with high affinity to the monolayers. For example, equilibrium dissociation constants of 6.3(±3) μM and 2.7(±0.5) μM were determined for bioadhesive MLV and ULV, respectively, with corresponding saturation occupancies of 3.7(±1) and 4.0(±0.2) pmoles liposomal collagen/ monolayer of 10 5 cells. (d) Following the retention of bioadhesive MLV at A431 monolayers for 24 h, it was found that: at 4°C, 24 h did not suffice to reach equilibrium, but at 37°C equilibrium binding was obtained within 3–5 h and there was quantitative liposome retention (per viable monolayer) thereafter. It is concluded that these liposomes are bioadhesive sustained-release carriers, as desired, meriting further cellular and in vivo studies.