Methotrexate loaded chitosan and chitin microspheres--in vitro characterization and pharmacokinetics in mice bearing Ehrlich ascites carcinoma.

Methotrexate (MTX) loaded chitosan and chitin microspheres were prepared. The physicochemical characteristics were affected by various parameters, e.g. stirring speed, concentration of chitosan and chitin. The t1/2 for in vitro release varied depending on the concentration of chitosan and chitin and the amount of glutaraldehyde used. The antitumour activity in Ehrlich ascites tumour bearing mice for MTX loaded chitosan microspheres was better when compared with plane MTX on oral administration. The plasma drug levels were sustained.

In vitro characterization of methotrexate-loaded poly(lactic acid) microspheres of different molecular weights.

Methotrexate-loaded poly (lactic acid) (PLA) microspheres were prepared from three different molecular weight PLAs using the emulsification-solvent evaporation method. The in vitro drug release could be controlled for up to 2 to 3 weeks. The release of the drug was dependent on the molecular weight of the polymer, the fastest release being from microspheres prepared with the lowest molecular weight PLA. This technique allows control of drug release with a single biodegradable homopolymer.

In vitro characterization of methotrexate loaded poly(lactic-co-glycolic) acid microspheres and antitumor efficacy in Sarcoma-180 mice bearing tumor.

Methotrexate (MTX) loaded poly (lactic-co-glycolic) acid (PLGA) microspheres were prepared by emulsion solvent evaporation technique. The mean diameter of the microspheres was affected by the type of emulsion stabilizer, polymer concentration, aqueous and organic phase volume and stirring speed. The in vitro release was triphasic and was dependent on copolymer composition and molecular weight of the polymer. Antitumor efficacy in Sarcoma-180 tumor bearing mice exhibited increased volume doubling time (18 +/- 2.7 days) compared to plain subcutaneous injection of methotrexate (8 +/- 0.7 days). Preliminary pharmacokinetic studies following subcutaneous administration of MTX loaded PLGA microspheres illustrated the controlled release of the drug. The studies demonstrated the feasibility of employing PLGA as an effective carrier for antineoplastic drug like methotrexate.

Antitumor and antifertility activities of plumbagin controlled release formulations.

With a view to increase efficiency and reduce toxicity of Plumbagin, an attempt was made to formulate plumbagin as a controlled release preparation using various carriers and test for their antitumor and antifertility activities. Niosomes and albumin microspheres were used as carriers. In vitro data showed promising results for these formulations thus they were taken up for in vivo assessment. Given at a dose of 5 mg/kg, ip the albumin microspheres showed promising antitumor and antifertility activity when compared to the niosomes on control. Animal survival data also indicated slight improvement in survival rate and thus antitumoral activity. Also, an interesting point was that the antifertility activity was affected through an antiovulatory action as seen from histopathological studies.

Reduced toxicity and enhanced antitumor efficacy of betacyclodextrin plumbagin inclusion complex in mice bearing Ehrlich ascites carcinoma.

Inclusion complex of plumbagin was prepared with betacyclodextrin employing neutralization method. The toxicity of the drug was reduced and the antitumor efficacy was enhanced on complexation with betacyclodextrin.

An analytical study of the neurosecretory cells of the brain of the mature larvae and diapause pupae of Amsacta collaris Hampson (Lepidoptera: Arctiidae) under different temperature regimes.

The neurosecretory cells (NSCs) of the brain of the mature larvae and 3 months old diapause pupae of Amsacta collaris Hampson (Lepidopera: arctiidae) have been studied under different temperature regimes (0, 7, 18, 37, and 42 degrees C), using paraldehyde fuchsin and performic acid resorcin fuchsin staining techniques. The 0 degree C is fatal to the larvae, and at 7 degrees C, within 24 h the quantity of NSM reduced considerably in all the subtypes of A-cells; activity started 3rd day onwards, and on 5th day, the A1-cells appeared loaded with NSM, the A2-cells moderately filled, but no change in A3-cells was observed. At 0 degree C, within 48 h or chilling, the NSCs of diapause pupae (DP) revealed a moderate amount of NSM with numerous, large vacuoles in the A1-cells and in some insects, the cells appeared gigantic in form; the A2- and A3-cells were moderately filled with NSM. After 1 week of chilling, at 0 degree C, the A1-cells appeared almost empty. The A1-cells of DP-kept at 7 degrees C and 18 degrees C respectively, discharged quickly all the previously stored NSM, within 2 days, hence appeared poorly filled. 3rd day onwards, a gradual increase in NSM was observed. After 15 days, a moderate amount of NSM in A1-, a large amount in A3-, and increased amount in A2-cells of the medial and lateral groups was observed. The 37 degrees C appeared to be the most suitable temperature at which all the cells show maximum activity in mature larvae and DP both, and contain a moderate amount of NSM in them. At 42 degrees C, the A1-cells in larvae and DP contain a moderate amount of NSM, A2-cells of the medial group a poor, and A2-cells of the lateral group, a depleted amount of NSM, the A3-cells, however, appeared heavily loaded. Later, the NSM decreased gradually in all the subtypes of A-cells. On 15th day, at 42 degrees C the A1-cells in DP revealed depletion of NSM, the A2-cells become totally inactive and lack NSM; the A3-cells a poor amount of NSM in them. The significance of these changes at different temperature regimes is discussed.

The neurosecretory cells and retrocerebral endocrine glands of Amsacta collaris Hampson (Lepidoptera: Arctiidae) during post-embryonic development.

Neurosecretory cells and retrocerebral endocrine glands of Amsacta collaris Hampson have been studied by using PF and PARF techniques in whole mounts and sections. On the basis of staining properties, three principal types of cells viz., A, B and C-types have been distinguished, which have been further classified into A-1, A-2, A-3, A-4, B-1, B-2 and C-1, C-2 subtypes respectively. The cells are arranged in 12-groups i.e. 2-medial, 2-lateral, 2-optic, 2-posterior, 2-ventral and 2-tritocerebral. The material elaborated in the medial, lateral, ventral and posterior groups of cells is stored in the outer part of the corpus allatum and that of the optic and tritocerebral, is stored in the corpus cardiacum. In addition to brain, distinct neurosecretory cells have been observed in the frontal and hypocerebral ganglia, and in the latter case they have been reported here probably for the first time in Lepidoptera. The corpora cardiaca are a pair of club-shaped or stellate bodies lying behind the brain, with which they are attached by NCC-I and NCC-II. The corpora cardiaca are composed of only a few intrinsic cells. Some nerves arise from the corpus cardiacum and innervate the gut dialator muscles, recurrent nerve, aorta and the adjacent organs. The corpora allata are oval in shape, attached to the corpora cardiaca via allatic nerve. In larval stages, each corpus allatum is a single lobed body which becomes many lobed in late pupa and adult stages. The gland is superficially innervated by the neurosecretory axons of cerebral origin which contain a large amount of NSM. Thus the outer part of the gland acts as a principal neurohaemal organ. The inner part of the corpus allatum is devoid of NSM.

Dynamics of the neurosecretory cells of the brain of Amsacta collaris Hampson (Lepidoptera: Artiidae) during post embryonic development.

A comprehensive account of the dynamics of the neurosecretory cells of the brain of Amsacta collaris Hampson, during post embryonic development has been given using largely PARF, as well as PF and PAVB techniques in whole mounts sections. On the basis of staining properties the neurosecretory cells have been distinguished into principal A, B and C types. These cell types have been further classified into A-1, A-2, A-3, and A-4; B-1, B-2, and C-1, C-2 subtypes. Occurrence of paired medial, lateral, optic, posterior, ventral and tritocerebral groups containing different types of cells in the brain of Amsacta collaris in specific development stages have been reported. It has been observed that in the 1st instar larvae, there is no distinction of subtypes of cells. The distinction of cells into respective subtypes starts from 2nd instar and onward. The number of cells are minimum in the 1st instar, which increases upto the sixth instar larva, and remain almost constant in the prepupa, and diapausing pupa. The maximum number of cells have been observed in the adult individuals. In addition to number and distribution, the secretory activity of different types of cells during post embryonic development have also been described.

The anatomy and histology of the ecdysial glands of Philosamia ricini (Hutt.) (Lepidoptera: Saturniidae) during the post embryonic development.

A comprehensive account of the anatomy and histophysiology of the ecdysial glands of Philosamia ricini during post embryonic development has been given. The study clearly indicates an increase in number of cells in each larval instar by endomitosis. The maximum number of cells are present in the 5th instar larvae. The cell size decreases before moulting in each instar. The size and shape of the cells of the glands vary considerably from individual to individual or even in the same individual. They are oval, elongate, polygonal in outline. Gland is collectively innervated by transverse nerves arising from the suboesophageal, prothoracic, mesothoracic and metathoracic ganglia as well as medial-1 and medial-2 nerves. The secretory activity of the glands is indicated by a large amount of cytoplasm with a developed brush border, having vacuoles at the periphery. The inactive glands have small amount of cytoplasm, without vacuoles and poorly developed brush border. The glands are absent in the newly moulted adults indicating that they degenerate before imaginal ecdysis.