Nano-strategies as Oral Drug Delivery Platforms for Treatment of Cancer: Challenges and Future Perspectives.

Oral drug administration is the oldest and widely used method for drug administration. The objectives behind developing an oral drug delivery for the treatment of cancer are to achieve low cost treatment by utilizing novel techniques to target cancer through gut-associated lymphoid tissue (GALT) and to enhance patient comfort and compliance through a hospital-free treatment leading to "Chemotherapy at Home." Unfortunately, due to the physiological environment of the GIT and physicochemical properties of drug candidate, the efficacy of oral drug delivery methods is limited in the treatment of cancer. Due to their low hydrophilicity, high P-gp efflux and restricted intestinal permeability most of the anti-cancer drugs fail to achieve oral bioavailability. The review focuses on the efforts, challenges, opportunities and studies conducted by scientists worldwide on the oral administration of anticancer medications via nanocarriers such as liposomes, SLNs and dendrimers, because of their potential to overcome the epithelial barrier associated with GALT, as well as the applications of different polymers in targeting the cancer. The oral delivery can set newer horizons in cancer therapy to make it more patient friendly.

Bifocal Stabilisation of Acute Acromioclavicular Joint Dislocation using Suture Anchor and Temporary K-Wires: A Retrospective Analysis.

Introduction: The acromioclavicular joint (ACJ) is a major link connecting the upper limb to the torso. The acromioclavicular and coracoclavicular (CC) ligaments help in stabilising the joint. We feel it is prudent to address both these ligament injuries, to achieve optimum result. This study was undertaken to analyse the results of a simple frugal surgical technique we used to deal with this injury considering stabilisation for both these ligaments. Materials and methods: In this retrospective study, skeletally mature patients with Type III, IV or V ACJ dislocations who underwent open reduction and stabilisation of the joint with temporary K-wires, repair of the capsule and augmentation of CC ligaments with suture anchors were included. Clinico-radiological and functional outcome was evaluated. Functional assessment of the upper limb was analysed using the Disabilities of Arm, Shoulder, and Hand Score (DASH), Constant shoulder score (CSS) and Oxford shoulder score (OSS). Results: Clinical and radiological evaluation of the 32 patients who had completed two years from the index surgery, was done. Out of the 37 patients included initially, five were lost in follow-up. Majority of the subjects included were males and type V was the most common injury. Mean pre-operative CC distance on the affected side was 13.92±4.94mm. In the immediate post-operative radiograph, it was 7.63±2.08mm and in the final follow- up was 9.36±2.75mm. Measurements were taken by two independent investigators and inter, and intra-observer reliability were analysed by Interclass correlation coefficient. Excellent functional outcome was noted despite the 1.81±1.50mm average loss of correction. At final follow-up, mean DASH score was 4.67±4.18, Oxford shoulder score was 44.06±2.44 and Constant shoulder score was 86.37±5.81. The severity of the injury had no significant effect on the functional outcome post our method of stabilisation and rehabilitation. Conclusion: Bifocal fixation restores the multidirectional stability of the disrupted ACJ. Adequate radiological reduction, good functional outcome and simplicity of execution make this technique an undemanding one for use in regular practice.

Enhanced Permeation of an Antiemetic Drug from Buccoadhesive Tablets by Using Bile Salts as Permeation Enhancers: Formulation Characterization, In Vitro, and Ex Vivo Studies.

Buccal bioadhesive bilayer tablets of prochlorperazine maleate were designed and formulated by using buccoadhesive polymers such as hydroxypropylmethyl cellulose, Carbopol 934P, and sodium alginate. Physicochemical characteristics like the uniformity of weight, hardness, thickness, surface pH, drug content, swelling index, microenvironment pH, in vitro drug release, and in vivo buccoadhesion time of the prepared tablets were found to be dependent on the type and composition of the buccoadhesive materials used. The effect of bile salts on the permeation was studied through porcine buccal mucosa and it was found that out of three bile salts incorporated (sodium glycholate, sodium taurocholate, and sodium deoxycholate), sodium glycholate enhanced the permeation rate of prochlorperazine maleate by an enhancement factor of 1.37.

Preparation and characterization of solid dispersions of carvedilol with PVP K30.

Solid dispersions in water-soluble carriers have attracted considerable interest as a means of improving the dissolution rate, and hence possibly bioavailability, of a range of hydrophobic drugs. The poor solubility of carvedilol leads to poor dissolution and hence variation in bioavailability. The purpose of the present investigation was to increase the solubility and dissolution rate of carvedilol for enhancement of oral bioavailability. In the present investigation solid dispersions with PVP K30 were prepared by solvent evaporation method. The physical mixture and solid dispersion (s) were characterized for drug-carrier interaction, drug content, solubility and dissolution rate. The solubility of drug increased with increasing polymer concentration. The dissolution rate was substantially improved for carvedilol from its solid dispersion compared with pure drug and physical mixture. As indicated from X-ray diffraction pattern and DSC thermograms carvedilol was in the amorphous form, which confirmed the better dissolution rate of solid dispersions. The solid dispersion was stable under accelerated storage conditions. The solid dispersion technique with PVP K30 as a carrier provides a promising way to enhance the solubility and dissolution rate of carvedilol.

Preparation and characterization of niosomes containing rifampicin for lung targeting.

Niosomes (non-ionic, surfactant-based vesicles) containing rifampicin of 8-15 microns in diameter were prepared using Span-85 and cholesterol in various molar fractions. The process variables that could affect the physical characteristics of niosomes and in vitro release of the drug from the niosomes were studied and optimized. In vivo distribution studies of the prepared niosomes found that 65% of the drug could be localized in the lungs by controlling the niosome size.

Bioadhesive polymer-grafted starch microspheres bearing isosorbide dinitrate for buccal administration.

A polymer-grafted mucoadhesive system bearing isosorbide dinitrate was prepared for buccal administration. Polymer grafting of starch microspheres modified drug release and surface characteristics of microspheres. Bioadhesion and factors affecting bioadhesion were studied. Process variables that could affect microsphere size, and as a result the release of the drug, were also studied. It was observed that compression of grafted starch microspheres modified drug release and extended drug action via slow release following buccal application. Prepared system(s) were characterized for drug release and in vivo performance and compared with conventional oral treatment. The systems were noted to be promising.

Polymeric pseudolatices bearing pilocarpine for controlled ocular delivery.

The pseudolatex-based ocular formulations of pilocarpine were prepared using different combinations of Eudragit RS 100 and polyvinyl pyrrolidone for prolonged and controlled release of the drug. The designed system was essentially based on polymeric pseudolatex dispersion. The process variables that effect the latex particle size, drug loading and release profiles of drug were studied. Preparations were evaluated for their in vitro performance with regard to release profile and diffusion co-efficient. The designed system exhibited linear relationship between cumulative drug release (Q) and square root of time (t0.5). The products selected on the basis of in vitro characterization were studied for in vivo performance evaluation. It was observed that the preparations exhibited in vivo prolonged therapeutic efficacy. Thus polymer based pseudolatices hold promise for controlled pilocarpine ocular delivery.