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Fulltext Advanced drug delivery to the lymphatic system: lipid-based nanoformulations

Ali Khan A, Mudassir J, Mohtar N, Darwis Y

Int J Nanomedicine, 2013;8:2733-44.
PMID: 23926431 DOI: 10.2147/IJN.S41521

The delivery of drugs and bioactive compounds via the lymphatic system is complex and dependent on the physiological uniqueness of the system. The lymphatic route plays an important role in transporting extracellular fluid to maintain homeostasis and in transferring immune cells to injury sites, and is able to avoid first-pass metabolism, thus acting as a bypass route for compounds with lower bioavailability, ie, those undergoing more hepatic metabolism. The lymphatic route also provides an option for the delivery of therapeutic molecules, such as drugs to treat cancer and human immunodeficiency virus, which can travel through the lymphatic system. Lymphatic imaging is useful in evaluating disease states and treatment plans for progressive diseases of the lymph system. Novel lipid-based nanoformulations, such as solid lipid nanoparticles and nanostructured lipid carriers, have unique characteristics that make them promising candidates for lymphatic delivery. These formulations are superior to colloidal carrier systems because they have controlled release properties and provide better chemical stability for drug molecules. However, multiple factors regulate the lymphatic delivery of drugs. Prior to lymphatic uptake, lipid-based nanoformulations are required to undergo interstitial hindrance that modulates drug delivery. Therefore, uptake and distribution of lipid-based nanoformulations by the lymphatic system depends on factors such as particle size, surface charge, molecular weight, and hydrophobicity. Types of lipid and concentration of the emulsifier are also important factors affecting drug delivery via the lymphatic system. All of these factors can cause changes in intermolecular interactions between the lipid nanoparticle matrix and the incorporated drug, which in turn affects uptake of drug into the lymphatic system. Two lipid-based nanoformulations, ie, solid lipid nanoparticles and nanostructured lipid carriers, have been administered via multiple routes (subcutaneous, pulmonary, and intestinal) for targeting of the lymphatic system. This paper provides a detailed review of novel lipid-based nanoformulations and their lymphatic delivery via different routes, as well as the in vivo and in vitro models used to study drug transport in the lymphatic system. Physicochemical properties that influence lymphatic delivery as well as the advantages of lipid-based nanoformulations for lymphatic delivery are also discussed.

Matched MeSH terms: Lymphatic System*
The lymphatic system of a species of amphistome

Lowe CY

Med J Malaya, 1965 Sep;20(1):56-7.
PMID: 4221417
Matched MeSH terms: Lymphatic System/anatomy & histology*
Mastomys natalensis as an experimental host for Brugia malaye subperiodic

Petrányi G, Mieth H, Leitner I

Southeast Asian J. Trop. Med. Public Health, 1975 Sep;6(3):328-37.
PMID: 1221502

Infective larvae of Brugia malayi subperiodic obtained by dissection of infected Aedes togoi were injected subcutaneously into the scrotal region of Mastomys natalensis. From altogether 58 infected male M. natalensis 81% showed consistently or intermittently detectable microfilaraemia, whereas in 19% of the animals no microfilaraemia could be detected at any stage. The mean prepatent period was 136 days; the microfilarial density varied from 1 to 535 per 20 c. mm blood. In those animlas with consistently detectable and in general higher microfilaraemia an average of 13.1 live adult worms were found, against an average of 6.4 adult worms in animals with intermittent detectable and in general lower microfilaraemia. An average of 1.5 worms was found in animals which at no stage showed detectable microfilaraemia. A correlation between worm burden and prepatent period could be observed in the individual groups. From the total of 520 live adult worms recovered at necropsy, 37% were found in the lungs, 29% in the parenchyma of the testes and 34% in the lymphatic system. 47% of live fertile female worms were found in the lymphatic system, whereas the majority, i.e; 52% of infertile female worms were detected in the lungs. In addition, 380 encapsulated dead worms were found, most of them (98%) in the lymphatic system. 61% of a total of 900 live and dead worms were found in the region of the lymphatic system.

Matched MeSH terms: Lymphatic System/parasitology
Comparison between Collagenase Injection and Partial Fasciectomy in the Treatment of Dupuytren's Contracture

Tay TK, Tien H, Lim EY

Hand Surg, 2015 Oct;20(3):386-90.
PMID: 26387998 DOI: 10.1142/S0218810415500288

A comparative study between two treatment methods (collagenase injection and open partial fasciectomy) for Dupuytren's contracture. This study will determine differences in clinical outcome, complication rate and patient satisfaction.

Matched MeSH terms: Lymphatic System
Fulltext Cavernous lymphangioma of the digits: a rare cause of macrodactyly

Leong, J.F., Levin, K.B., Rajkumar V., Abdullah, S., Jamari, S.

Medicine & Health, 2019;14(2):261-265.
MyJurnal

Cavernous lymphangioma is a congenital malformation of lymphatic system causing dilated lymphatic sinuses that involve the skin and subcutaneous tissues. This was an interesting case of dystrophic macrodactyly of the left ring and little finger in a 18-month-old girl who presented with swollen and sausage like fingers deformity which turned out to be an isolated cavernous lymphangioma. This tumor, although rare to occur in the extremeties, must be differentiated from other congenital vascular lesions of the hand that include arteriovenous malformations and hemangiomas. Diagnosis should be solely based on histopathological analysis of the excised tissue mass. Surgical excision is usually necessary for satisfactory functional and cosmetic outcome

Matched MeSH terms: Lymphatic System
Fulltext Lymphangioma of an unusual site: a case report

Jahanbakhsh J, Salmah WM, Abubakar NT, Samsudin H

Malaysian Journal of Paediatrics and Child Health, 2016;22(1):58-65.
MyJurnal

Lymphangiomas are hamartomatous congenital malformations of the lymphatic system that usually involve subcutaneous tissues of cervico-facial region. Rarely, it can be found in subcutaneous tissue of proximal extremities, the buttocks and the trunk. Magnetic Resonance Imaging (MRI) is the best modality to assess the tumor specification and extension. We report a case of lymphangioma at a rare site with its radiological features and patient responsed to the sclerosant therapy.

Matched MeSH terms: Lymphatic System
Histomorphology of the lymphoid tissues of broiler chickens in Kelantan, Malaysia

Masum M, Khan MZI, Abdur Rahman Aziz, Mohd Zahirul Islam Khan, Nasrin M, Siddique MNH, et al.

Sains Malaysiana, 2014;43:1175-1179.

The present research has been designed to understand the histomorphological development of lymphatic tissues of Cobb 500 strains of postnatal broiler chickens, aged between day old and D14 of Kelantan, Malaysia by gross and histological study. In the present study, it was found that the gross weight, length and width of the thymus, bursa of Fabricius and spleen were increased with the advancement of ages of the broiler chickens and was found higher from D14 to D28. Fine septa of connective tissue divide the thymus into lobes and lobules. The cortex of lobule is densely populated with lymphocytes. The bursal follicles were composed of a peripheral cortex which was rich in bursal cells and centrally depopulated medulla. The mucosal folds of the bursa were lined by pseudostratified columnar epithelium. The spleen has two compartments, the red and white pulp. The red pulp consisted principally of red blood cells, while the majority of the populations of white pulp were the lymphocytes. The histological mean length and width of the thymic lobules, bursal follicles and white pulp of the spleen were grown faster with the advancement of ages at D14 and D28. In conclusion, the increment of gross and histological parameters of lymphoid organs of broilers in the present study was due to aging of broilers.

Matched MeSH terms: Lymphatic System
Brugia tupaiae spn. n. (Nematoda: Filarioidea) in tree shrews (Tupaia glis) from Malaysia

Orihel TC

J Parasitol, 1966 Feb;52(1):162-5.
PMID: 5910449
Matched MeSH terms: Lymphatic System
Enhanced oral bioavailability and intestinal lymphatic transport of a hydrophilic drug using liposomes

Ling SS, Magosso E, Khan NA, Yuen KH, Barker SA

Drug Dev Ind Pharm, 2006 Mar;32(3):335-45.
PMID: 16556538

A liposome system was evaluated for oral delivery of a poorly bioavailable hydrophilic drug. The system was prepared from proliposome, which consisted of negatively charged phosphatidylcholine, whereas cefotaxime was chosen as the model drug. An in vivo study was carried out on nine rats according to a three-way crossover design to compare the oral bioavailability of cefotaxime from the liposomal formulation with that of an aqueous drug solution and a physical mixture of cefotaxime with blank liposomes. The results indicated that the extent of bioavailability of cefotaxime was increased approximately 2.7 and 2.3 times compared with that of the aqueous solution and the physical mixture, respectively. In a separate study, simultaneous determination of cefotaxime in intestinal lymph (collected from the mesenteric lymph duct) and in plasma (collected from the tail vein) revealed that its concentration was consistently higher in the lymph than in the plasma when administered via the liposomal formulation, whereas the reverse was observed with the aqueous solution. Thus, the results indicated that the liposomes system has the potential of increasing the oral bioavailability of poorly bioavailable hydrophilic drugs and also promote their lymphatic transport in the intestinal lymph.

Matched MeSH terms: Lymphatic System/metabolism*
Fulltext Lymphatic pathology in asymptomatic and symptomatic children with Wuchereria bancrofti infection in children from Odisha, India and its reversal with DEC and albendazole treatment

Kar SK, Dwibedi B, Das BK, Agrawala BK, Ramachandran CP, Horton J

PLoS Negl Trop Dis, 2017 Oct;11(10):e0005631.
PMID: 29059186 DOI: 10.1371/journal.pntd.0005631

BACKGROUND: Once interruption of transmission of lymphatic filariasis is achieved, morbidity prevention and management becomes more important. A study in Brugia malayi filariasis from India has shown sub-clinical lymphatic pathology with potential reversibility. We studied a Wuchereria bancrofti infected population, the major contributor to LF globally.
METHODS: Children aged 5-18 years from Odisha, India were screened for W. bancrofti infection and disease. 102 infected children, 50 with filarial disease and 52 without symptoms were investigated by lymphoscintigraphy and then randomized to receive a supervised single oral dose of DEC and albendazole which was repeated either annually or semi-annually. The lymphatic pathology was evaluated six monthly for two years.
FINDINGS: Baseline lymphoscintigraphy showed abnormality in lower limb lymphatics in 80% of symptomatic (40/50) and 63·5% (33/52) of asymptomatic children. Progressive improvement in baseline pathology was seen in 70·8, 87·3, 98·6, and 98·6% of cases at 6, 12, 18, and 24 months follow up, while in 4·2, 22·5, 47·9 and 64·8%, pathology reverted to normal. This was independent of age (p = 0·27), symptomatic status (p = 0·57) and semi-annual/bi-annual dosing (p = 0·46). Six of eleven cases showed clinical reduction in lymphedema of legs.
INTERPRETATION: A significant proportion of a young W. bancrofti infected population exhibited lymphatic pathology which was reversible with annual dosage of DEC and albendazole. This provides evidence for morbidity prevention & treatment of early lymphedema. It can also be used as a tool to improve community compliance during mass drug administration.
TRIAL REGISTRATION: ClinicalTrials.gov No CTRI/2013/10/004121.

Matched MeSH terms: Lymphatic System/pathology*
Fulltext Pathology of lymphatic filariasis

Mak JW

International e-Journal of Science, Medicine & Education, 2012;6 Suppl:S80-86.
MyJurnal

Developing and adult worms of the human lymphatic filarial parasites (Wuchereria bancrofti,
Brugia malayi, and Brugia timori) are located mainly in the lymphatic system and occasionally in aberrant sites like subcutaneous and conjunctival cysts. Lymphatic
pathology ranging from dilatation of lymphatic channels and lymphangiectasia are detected on ultrasonography in apparently healthy, amicrofilaraemic, but filarial antigen positive individuals in endemic areas. Microfilariae are distributed in various organs and may be associated with immune mediated pathology at these sites; tropical pulmonary eosinophilia is characterized by intense immune mediated destruction of microfilariae in the lung parenchyma. In the spleen and other sites, nodular granulomatous lesions can occur where microfilariae are trapped and destroyed. The finding of Wolbachia endosymbionts in all stages of lymphatic filarial parasites has provided new insight on the adverse reactions
associated with anti-filarial chemotherapy. Inflammatory molecules mainly lipopolysaccharide (LPS)-like molecules released from endosymbionts on death of the
parasites are largely responsible for the adverse reactions encountered during anti-filarial chemotherapy. Prenatal tolerance or sensitization to parasite derived molecules can immune-modulate and contribute to both pathology and susceptibility/resistance to infection. Pathological responses thus depend not only on exposure to filarial antigens/infection, but also on host-parasiteendosymbiont factors and to intervention with antifilarial treatment. Treatment induced or host mediated death of parasites are associated with various grades of inflammatory response, in which eosinophils and LPS from endosymbionts play prominent roles, leading to death of the parasite, granulomatous formation, organization and fibrosis. The non-human primate (Presbytis spp.) model of
Brugia malayi developed for the tertiary screening of anti-filarial compounds has provided unique opportunities for the longitudinal study of the pathology associated with lymphatic filariasis. The pathology in this non-human primate model closely follows that seen in
human lymphatic filarial infections and correlates with clinical evidence of lymphatic pathology as detected with ultrasonography. These studies also show that successful treatment as detected by loss of motility and calcification of worms on ultrasonography is associated with reversal of early dilatations of lymphatic channels.

Matched MeSH terms: Lymphatic System