Topical Drug Delivery to the Breast

Purpose: One purpose of this study was to assess changes in body composition throughout an off-season of two consecutive seasons, by measuring changes in body mass, fat mass, and lean body mass before and after a 16-week off-season training program. The second purpose of this study was to assess changes in macronutrient composition. Methods: 46 male college football players participated in this study during Season-1. 29 male college football players participated in this study during Season-2. A pre-test, post-test study design tracked body composition from post-season through offseason. Results: Significant changes in lean mass were not observed during the offseason training program. Surprisingly, the change in muscle area at the 66% site of the lower leg significantly increased in area. Total body mass and body fat did not change during the off-seasons. Conclusion: No significant changes in total body lean mass and leg lean mass were observed during a 16-week offseason training program. Because of the low number of participants, comparisons across groups, linemen and skill players, and upper- and lower-classmen were not made. Surprisingly, the change in muscle area at the 66% site of the lower leg significantly increased in area, an indication that the gastrocnemius and soleus muscle increased in mass. A significant difference in macronutrient composition was only found in fat consumption

Transpapillary (Nipple) Delivery of Macromolecules to the Breast: Proof of Concept Study

Localized drug delivery to the breast can maximize drug concentration at the target site and minimize systemic drug distribution. To this end, the study explored the feasibility of delivering macromolecules to the breast through mammary papilla (nipple). The in vitro penetration of model macromolecules (inulin, dextran, ovalbumin, and bovine serum albumin) varying in molecular weight from 5 to 67 kDa was studied using excised porcine and human mammary papilla. The penetration of macromolecules decreased with increase in molecular weight. The penetration of the macromolecules was significantly higher through the mammary papilla in comparison to breast skin. In vitro penetration of the macromolecules was similar in human and porcine mammary papilla. Iontophoresis was used to enhance the transport of bovine serum albumin (BSA) through the mammary papilla. The flux and cumulative amount permeated was increased by 2- to 4-fold by iontophoresis. The macromolecules were transported through the ducts and the surrounding connective tissue in the mammary papilla. Overall, the results from this study for the first time demonstrate the feasibility of delivering macromolecules through the mammary papilla. These findings have implications for developing safe and effective localized therapeutic approaches for breast cancer

Fluorescence microscopic images of nipple.

<p>Fluorescence microscopic images of 7–8 µm thick cryosections of porcine (A) and human (B) nipple after treatment with the fluorescent dyes, SRB (upper panel in A and B) and NR (lower panel in A and B). Sections were taken from the entire length of the nipple starting from the tip to the base of the nipple. (Bar = 100 µm); SRB- sulforhodamine; NR- Nile red.</p

Impact of Dendrimers on Solubility of Hydrophobic Drug Molecules

Adequate aqueous solubility has been one of the desired properties while selecting drug molecules and other bio-actives for product development. Often solubility of a drug determines its pharmaceutical and therapeutic performance. Majority of newly synthesized drug molecules fail or are rejected during the early phases of drug discovery and development due to their limited solubility. Sufficient permeability, aqueous solubility and physicochemical stability of the drug are important for achieving adequate bioavailability and therapeutic outcome. A number of different approaches including co-solvency, micellar solubilization, micronization, pH adjustment, chemical modification, and solid dispersion have been explored toward improving the solubility of various poorly aqueous-soluble drugs. Dendrimers, a new class of polymers, possess great potential for drug solubility improvement, by virtue of their unique properties. These hyper-branched, mono-dispersed molecules have the distinct ability to bind the drug molecules on periphery as well as to encapsulate these molecules within the dendritic structure. There are numerous reported studies which have successfully used dendrimers to enhance the solubilization of poorly soluble drugs. These promising outcomes have encouraged the researchers to design, synthesize, and evaluate various dendritic polymers for their use in drug delivery and product development. This review will discuss the aspects and role of dendrimers in the solubility enhancement of poorly soluble drugs. The review will also highlight the important and relevant properties of dendrimers which contribute toward drug solubilization. Finally, hydrophobic drugs which have been explored for dendrimer assisted solubilization, and the current marketing status of dendrimers will be discussed

Transpapillary Drug Delivery to the Breast

<div><p>The study was aimed at investigating localized topical drug delivery to the breast via mammary papilla (nipple). 5-fluorouracil (5-FU) and estradiol (EST) were used as model hydrophilic and hydrophobic compounds respectively. Porcine and human nipple were used for in-vitro penetration studies. The removal of keratin plug enhanced the drug transport through the nipple. The drug penetration was significantly higher through the nipple compared to breast skin. The drug’s lipophilicity had a significant influence on drug penetration through nipple. The ducts in the nipple served as a major transport pathway to the underlying breast tissue. Results showed that porcine nipple could be a potential model for human nipple. The topical application of 5-FU on the rat nipple resulted in high drug concentration in the breast and minimal drug levels in plasma and other organs. Overall, the findings from this study demonstrate the feasibility of localized drug delivery to the breast through nipple.</p></div

Permeation of 5-FU through excised breast tissue.

<p>In-vitro permeation of 5-FU through porcine (A) and human (B) nipple after removing the keratin plug (KR), nipple with keratin plug, and breast skin. Each data point is represented as mean ± SEM (n = 3–4). † is significant in comparison to the results from nipple with keratin plug; *is significant in comparison to skin. The values are significant at p<0.05, by one-way ANOVA.</p

Permeation of EST through excised breast tissue.

<p>In-vitro permeation of EST through porcine (A) and human (B) nipple after removing keratin plug (KR), nipple with keratin plug, and breast skin. Each data point is represented as mean ± SEM (n = 3–4). † is significant in comparison to the results from nipple with keratin plug; *is significant in comparison to corresponding skin group. The values are significant at p<0.05, by one-way ANOVA.</p